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Gossypol Toxicity from Cottonseed Products

Ivana Cristina N. Gadelha, Nayanna Brunna S. Fonseca, Silvia Catarina S. Oloris and 2 more

The Scientific World Journal · 2014

doi:10.1155/2014/231635

Abstract

Gossypol is a phenolic compound produced by pigment glands in cotton stems, leaves, seeds, and flower buds ( Gossypium spp.). Cottonseed meal is a by-product of cotton that is used for animal feeding because it is rich in oil and proteins. However, gossypol toxicity limits cottonseed use in animal feed. High concentrations of free gossypol may be responsible for acute clinical signs of gossypol poisoning which include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. However, the most common toxic effects is the impairment of male and female reproduction. Another important toxic effect of gossypol is its interference with immune function, reducing an animal’s resistance to infections and impairing the efficiency of vaccines. Preventive procedures to limit gossypol toxicity involve treatment of the cottonseed product to reduce the concentration of free gossypol with the most common treatment being exposure to heat. However, free gossypol can be released from the bound form during digestion. Agronomic selection has produced cotton varieties devoid of glands producing gossypol, but these varieties are not normally grown because they are less productive and are more vulnerable to attacks by insects.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 27, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Cotton (Gossypium spp.) is an arborous plant from the Malvaceae family. It is one of the earliest plants that were cultivated by man and it has been used for over 4,000 years. It is primarily cultivated for fiber used in the textile industry and the oil from the cotton seed. The genus Gossypium spp. includes many species distributed throughout the world, but only four species are grown for cotton fiber: Gossypium hirsutum L., Gossypium barbadense L., Gossypium arboreum L., and Gossypium herbaceum L. The most economically important cotton species is G. hirsutum, which is grown to produce 90% of the world's cotton. Cotton fiber and oil production generate byproducts rich in fat from oil and protein which are used for animal feeding. However, this plant contains a toxic compound, gossypol.

2. Chemistry of Gossypol

Gossypol is a phenolic compound that was first isolated in 1899. The name is derived from the plant genus scientific name (Gossypium) combined with the ending “ol” from phenol. Gossypol has a 518.55 Dalton molecular weight, has a yellow pigment, is crystalline, is insoluble in water and hexane, is soluble in acetone, chloroform, ether, and methyl ethyl ketone (butanone), and is partly soluble in crude vegetable oils. The chemical formula is C30H30O8, and the chemical structural formula is 2,2′-bis(8-formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene) (Figure 1).

Gossypol is produced by pigment glands in cotton stems, leaves, seeds, and flower buds. The pigment glands are small black spots distributed throughout the cotton plant but their greatest concentration is in the seeds. The seed of G. barbadense may contain up to 34 g of gossypol/kg. Gossypol promotes several toxic effects in vertebrates but provides the cotton plant with resistance to pests. The pigment glands produce additional phenolic pigments (at least 14), but they are at concentrations well below the concentration of gossypol and thus have little toxicological significance.

Gossypol is a mixture of two enantiomers, (−) and (+) gossypol. The (−) gossypol enantiomer is more slowly eliminated, although it is the most biologically active form. Consequently, it is more toxic than the (+) gossypol. The Gossypium species produces both enantiomers in varying proportions, which is genetically determined. For example, the (−) gossypol proportion ranges from 33.8 to 47.0% in the seeds of upland variety (G. hirsutum) and from 24.9 to 68.9% in the seeds of G. barbadense.

Two gossypol forms have been observed, free and bound. The bound form is produced via covalent bonds between gossypol and the free epsilon-amino groups from lysine and arginine through the browning or Maillard reaction. However, this reaction reduces the availability of amino acids for absorption by the animal with lysine being the most affected.

Total gossypol production is influenced by several factors, including weather conditions and cotton species. Considering weather conditions, gossypol production is positively correlated with the rainfall rate and negatively correlated with temperature. Regarding variation among cotton species, G. barbadense has higher gossypol concentrations than G. hirsutum. On the other hand, cotton storage slightly decreases the free gossypol content.

3. Gossypol in Cotton Products

The free gossypol content in whole cotton seeds varies among the many cotton varieties; gossypol concentrations range from 0.02 to 6.64%. Cottonseed may contain concentrations greater than 14,000 mg/kg of total gossypol and 7,000 mg/kg of free gossypol. However, after oil extraction from the seeds, up to 0.6% is available following solvent extraction, but approximately 0.06% is available, if the extraction process involves mechanical pressure and heat treatment.

In addition to its harmful effects, gossypol and its derivatives have potential therapeutic use. These compounds showed in vitro action against some viruses such as human immunodeficiency virus and H5N1 influenza virus and several bacteria and yeasts. Gossypol is a promising treatment for leukemia, lymphoma, colon carcinoma, breast cancer, myoma, prostate cancer, and other malignancies. Furthermore, it was used in China, in 1970, to treat uterine fibroids, endometriosis, and uterine bleeding in women.

4. Toxicokinetics

The gossypol absorption rate is inversely proportional to the amount of iron in the diet, and dietary supplementation with ferrous sulfate inactivates free gossypol. In ruminants, microbial fermentation in the rumen binds dietary free gossypol with proteins, but it is not known whether the bound form can be absorbed by the intestines or the microorganisms can release free gossypol from the bound form. The absorbed gossypol accumulates in the liver and kidneys. The primary gossypol excretion route is through bile; it is then eliminated through feces after conjugation with glucuronides and sulfates. In rats dosed orally with 5 mg of both racemic forms of gossypol, 70.4% of (+) and 80.2% of (−) gossypol were excreted in the feces within five days, whereas 2.30% of (+) and 2.79% of (−) gossypol were excreted in the urine. Small amounts of gossypol are also excreted in expired air. Little to no gossypol is excreted in the milk. The half-lives (t 1/2) of total (+) and (−) gossypol in rats following a single intravenous dose were estimated as 25.26 hours and 10.53 hours, respectively.

5. Gossypol Poisoning

Cottonseed includes sufficiently high gossypol concentrations to produce acute poisoning. However, there are cumulative effects of dietary gossypol and toxicity which can occur following an ingestion period of one to three months. Gossypol poisoning has been reported in many species, including broiler chicks, pigs, dogs, sheep, and goats. Monogastric animals, such as pigs, birds, fish, and rodents, are more susceptible to gossypol toxicity than ruminants. Moreover, young ruminants are more sensitive to gossypol compared with adult ruminants because gossypol is not bound during ruminal fermentation, as it occurs in animals with fully functional rumens. However, if the gossypol intake overwhelms the ruminal detoxification capacity, free gossypol may be absorbed at hazardous concentrations even in adult ruminant animals.

General signs of acute toxicity are similar among animal species and include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. Heart failure was reported in calves, lambs, and dogs.

The postmortem findings in ruminants include pulmonary edema, yellowish liquid in the chest and peritoneal cavities, gastroenteritis, centrilobular liver necrosis, and hypertrophic cardiac fiber degeneration. In calves, the major pathologic findings are ascites, visceral edema, acute centrilobular hepatocyte necrosis, kidney damage, and cardiovascular lesions. Increased pneumonia has also been observed, likely due to an increased sensitivity to secondary infections.

Pigs may present reduced weight gain, anorexia, respiratory distress, cardiac insufficiency, coughing, and exercise intolerance. Necropsy findings include fluid accumulation in the body cavities; edema and congestion in the liver, lung, and spleen; and cardiac hypertrophy with degenerated muscle fiber.

Anemia is often observed in animals fed cottonseed. In fact, gossypol is a highly reactive compound that readily binds to minerals and amino acids. Binding with iron forms a gossypol-iron complex, which inhibits the absorption of this metal. The consequent iron deficiency affects erythropoiesis. Furthermore, gossypol promotes increased erythrocyte fragility. Gossypol also stimulates the eryptosis (apoptosis-like erythrocyte death) by increasing cytosolic Ca2+ activity resulting in cell membrane scrambling and contraction, which contributes to anemia.

Gossypol also affects thyroidal metabolism. Some studies with male and female rats showed decreased blood concentrations of T4 and T3 after dosing with gossypol. On the other hand, gossypol dosing resulted in increased T3 serum concentrations without affecting T4 in rats and sheep. The histopathological evaluation of thyroid glands from male rats dosed with gossypol revealed follicular degeneration and atrophy. The thyrotropic cells in the pituitary gland, which are specialized for TSH synthesis and secretion, showed hypertrophy, hyperplasia, and degranulation after gossypol dosing in rats.

Certain clinical signs of gossypol poisoning have been attributed to reduced antioxidants in tissues and increased reactive oxygen species formation, which produces lipid peroxidation. At high concentrations, gossypol also impairs energy generation from oxidative metabolism by interfering with enzymatic activity in the mitochondrial electron transport chain and oxidative phosphorylation. Furthermore, gossypol decreases the contraction force of the heart and the extent of contraction of cardiac fibers.

6. Liver Damage

In addition to such effects, gossypol is hepatotoxic (Table 1). Ascites and hepatocyte degeneration (strong cytoplasmic eosinophilia and nuclear pyknosis) were observed in rats that received a single intraperitoneal gossypol dose of 25 mg/kg BW or 30 mg/kg BW. Rats that received lower gossypol doses (15 mg/kg/day for four weeks or 30 mg/kg/day for two weeks) showed morphological changes in the liver, as observed through electron microscopy, which were characterized by mitochondrial vacuolation, an enlarged endoplasmatic reticulum, an expanded perinuclear space, and collagen fiber proliferation in the perisinusoidal space. Chickens fed a diet with 0.1% free gossypol for 21 days had increased plasma gamma glutamyltransferase activity and liver lipidosis. Broilers that received a diet with 0.4% total gossypol for 20 days had greater liver weights.

7. Reproductive Effects

Gossypol affects male and female gametogenesis and promotes embryo lesions. In the 1950s, China underwent a sharp drop in the birthrate in many rural areas where humans were consuming cottonseed oil containing gossypol. This observation was initially associated with male infertility caused by gossypol in the cottonseed oil that they were consuming. Gossypol has been investigated for use as a male contraceptive in a number of experimental studies.

The gossypol toxicity for male reproduction (Table 2) was reported in several studies showing that it inhibits spermatogenesis, which decreases the sperm count and spermatozoid motility and viability. The male antifertility effect is dose and time dependent; in effective doses, gossypol causes infertility by inhibiting sperm motility, decreasing sperm concentrations, inducing specific mitochondrial injury to the sperm tail, and damaging the germinal epithelium. However, such effects are reversible when gossypol is no longer ingested. Furthermore, gossypol administration to male rats did not interfere in the embryonic and fetal development of untreated dam offspring.

The deleterious effects on male reproduction have not been observed for all animals fed cottonseed meal. In adult male goats and sheep fed a diet with 0.5 kg/animal/day cottonseed meal for 120 consecutive days, no detrimental effects on semen volume, sperm concentration, motility, and morphology.

The gossypol-mediated spermatozoid disturbance mechanism includes the inhibition of release and utilization of ATP by the sperm cells. Another effect of gossypol is the reduction of cellular and microtubular β-tubular content in spermatocytes and spermatids. Furthermore, gossypol inhibits calcium influx and Mg-ATPase and Ca-Mg-ATPase activity in spermatozoid plasmatic membranes. Abnormal spermatozoids are produced because gossypol produces ultrastructural alterations in the nuclear membrane, endoplasmic reticulum, and mitochondria. In cultivated Sertoli cells from piglets, gossypol also decreases cellular oxidase activity and damages the DNA. Reduced nuclear expression of androgen receptors was observed in Leydig cells, Sertoli cells, and myoid cells from rats fed gossypol-rich cottonseed flour.

Gossypol also affects female reproduction (Table 3), and ruminant females tolerate higher dietary gossypol concentrations than nonruminant females, probably due to the ruminal detoxification. Female exposure to gossypol has been associated with interference with the estrous cycle, pregnancy, and early embryonic development. Gossypol interfered with rodent estrous cycles and pig granulosa cell function. Furthermore, ovaries from heifers fed cottonseed meal had fewer large follicles (>5 mm) than heifers fed soybean meal. Gossypol affected in vitro ovarian steroidogenesis as well as bovine oocyte cumulus expansion and nuclear maturation.

Previous studies have shown that gossypol interferes with embryonic development. In fact, gossypol may reach the uterine fluids through the maternal circulation. A gossypol-mediated embryotoxic effect has been observed in in vitro and in vivo studies. The early pregnancy loss promoted by gossypol is not due exclusively to direct damage to embryos but also to interference with implantation of the embryo. However, this compound significantly reduced the fetal body weight in pregnant mice, but no fetal abnormalities were observed.

The probable mechanism for gossypol embryotoxicity is through direct embryonic cytotoxicity. This cytotoxic effect might be promoted by (1) generation of reactive oxygen species inducing oxidative stress, (2) intercellular communication disruption, (3) apoptosis induction, or (4) interference with ionic transport in membranes, which increases intracellular calcium.

8. Immunotoxicity

Gossypol may cause a reduced number of leukocytes and primarily lymphocytes, which affects the immunocompetence of the organism. In vivo and in vitro mouse experiments also demonstrated that gossypol has immunosuppressive activity, which operates by affecting lymphocytes through inhibiting proliferation and inducing apoptosis. Mice that received gossypol had significantly decreased numbers of lymphocytes in the thymus and mesenteric lymph nodes, in the total spleen cell population, and in the capacity of blood and lymphatic cells to produce antibodies after sheep erythrocyte immunization. Furthermore, the spleen and lymph nodes from mice receiving gossypol had decreased CD4+ thymocyte populations and increased CD8+ lymphocyte populations.

The interference of gossypol with lymphocytes influence immune function as observed in a number of studies. After inoculation with Brucella abortus smooth strain 99 (S99), specific anti-Brucella antibody production was impaired in lambs and calves fed cottonseed meal. Mice treated with gossypol had decreased IgM and IgG production after sheep erythrocyte immunization. Men treated with gossypol as a male contraceptive showed reduced IgG titers which could be associated with altered lymphocytes.

In vitro murine macrophage proliferation was inhibited by gossypol. Furthermore, rat peritoneal macrophages incubated with gossypol inhibited arachidonic acid metabolism and prostaglandin E2 production. On the other hand, macrophage chemotaxis induced by Edwardsiella ictaluri challenge was increased in channel catfish (Ictalurus punctatus) fed cottonseed or receiving gossypol, but catfish were unaffected by gossypol in another study. Gossypol also increased serum lysozyme activity in channel catfish following an E. ictaluri challenge.

9. Preventive Procedures

The preventive procedures at this time involve the treatment of cottonseed products to decrease the concentrations of free gossypol through the use of heat and pressure in the processing of these products (Table 4). Agronomic selection has produced cotton varieties devoid of glands producing gossypol, but these varieties are less grown because they are not as productive and are more vulnerable to attacks by insects. One alternative is the selection and use of cotton varieties containing a relatively high (+) to (−) gossypol enantiomer ratio. The directive 2002/32 of the European Union (2002L0032 - EN - 26.02.2013 - 017.001) states that the maximum free gossypol concentrations for cottonseed are 5,000 ppm and 1,200 ppm for cottonseed meal or cake and, for complete feeding stuffs, are 20 ppm for laying hens and piglets, 60 ppm for rabbits and pigs, 100 ppm for poultry and calves, and 500 ppm for cattle, sheep, and goats.

Processing including heat treatment and extrusion process can reduce free gossypol concentrations in cottonseed. However, it is possible that the conjugate formed can release free gossypol during digestion. In fact, cows fed diets containing whole cottonseed with similar total gossypol concentrations but different free gossypol concentrations had similar total plasma gossypol. Furthermore, even though the extrusion process reduced free gossypol concentration but not the total gossypol concentration; broiler chicks fed extruded cottonseed meal or feed-grade cottonseed meal showed decreased body weight gain, increased feed intake, and inefficient feed conversion rate.

Radiation treatment using gamma or electron beam irradiation may reduce free gossypol concentrations. In fact, gossypol irradiation reduced in vitro prooxidative activity and embryotoxicity in mice. The mechanism for gossypol destruction through radiation is unknown, but it has been speculated that gossypol molecule aggregation, gossypol cross-linking with other molecules, and gossypol molecule fragmentation or breakdown may produce such destruction. On the other hand, ammoniation, which is a procedure that is used to reduce aflatoxin content of food, increased cottonseed meal toxicity in dairy cattle.

Some fungus may reduce free gossypol concentrations in cottonseed meal by fermentation, including Aspergillus niger, Aspergillus oryzae, Candida tropicalis, Saccharomyces cerevisiae, and Geotrichum candidum. The use of fermented cottonseed meal to feed animals seems to be safe. However, while these microorganisms could be used to reduce free gossypol concentration in cottonseed meal, they are not currently commercially available.

Supplementation with ferric sulfate reduces free gossypol concentrations in food due to ferric sulfate binding with reactive groups from gossypol, which forms a conjugate. The recommendation for supplementation is 1 mol of gossypol for each mol of iron, which could increase the maximum concentration of gossypol from 50 to 150 ppm for laying birds and from 100 ppm to 400 ppm for pigs and poultry. Additional nutrients may be used for dietary supplementation to reduce gossypol availability. Supplementing the diet with 1 mg of sodium selenite per day in adult sheep reduced the gossypol toxicity affecting semen quality. Dietary vitamin E supplementation at 4000 IU/bull/day also reversed the negative effects of gossypol on sperm production and semen quality of bulls and reversed the increased erythrocyte osmotic fragility in heifers promoted by feeding cottonseed meal.

Gossypol was produced as a conjugate with bovine serum albumin for vaccines. This conjugate induces antibody production against gossypol in rats, but the immunized animals were more sensitive to the acute hepatotoxic effect of gossypol.

10. Conclusions and Future Research Directions

The ingestion of gossypol present in cottonseed and its products (cakes and meal) may promote clinical poisoning, liver damage, male and female reproductive toxicity, and immunological impairment. The acute poisoning is not currently a significant problem but the reproductive damage causes serious economic losses to the livestock industry. Even though the male reproductive toxicity is well known, there is a need for more studies to understand the female reproductive damage promoted by gossypol. The immunotoxicity of gossypol is far from being completely elucidated, but it impacts animals by reducing their resistance to infections and by impairing the efficiency of vaccines. Extensive research is needed to develop more efficient and inexpensive technologies to reduce gossypol toxicity.

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    Deoras DP, Young-Curtis P, Dalvi RR, Tippett FE. Effect of gossypol on hepatic and serum γ-glutamyltransferase activity in rats. Veterinary Research Communications. 1997;21(5):317-323.

    Not in our library10.1023/a:1005856119553

  46. 46.

    Fonseca NBS, Gadelha ICN, Oloris SCS, Soto-Blanco B. Effectiveness of albumin-conjugated gossypol as an immunogen to prevent gossypol-associated acute hepatotoxicity in rats. Food and Chemical Toxicology. 2013;56:149-153.

    Not in our library10.1016/j.fct.2013.02.010

  47. 47.

    El-Sharaky AS, Newairy AA, Elguindy NM, Elwafa AA. Spermatotoxicity, biochemical changes and histological alteration induced by gossypol in testicular and hepatic tissues of male rats. Food and Chemical Toxicology. 2010;48(12):3354-3361.

    Not in our library10.1016/j.fct.2010.09.004

  48. 48.

    Hahn DW, Rusticus C, Probst A. Antifertility and endocrine activities of gossypol in rodents. Contraception. 1981;24(1):97-105.

    Not in our library10.1016/0010-7824(81)90072-x

  49. 49.

    Heywood R, Lloyd GK, Majeed SK, Gopinath C. The toxicity of gossypol to the male rat. Toxicology. 1986;40(3):279-284.

    Not in our library10.1016/0300-483x(86)90060-0

  50. 50.

    Gåfvels M, Wang J, Bergh A, Damber JE, Selstam G. Toxic effects of the antifertility agent gossypol in male rats. Toxicology. 1984;32(4):325-333.

    Not in our library10.1016/0300-483x(84)90084-2

  51. 51.

    Chenoweth PJ, Risco CA, Larsen RE, Velez J, Tran T, Chase CC. Effects of dietary gossypol on aspects of semen quality, sperm morphology and sperm production in young Brahman bulls. Theriogenology. 1994;42(1):1-13.

    Not in our library10.1016/0093-691x(94)90657-5

  52. 52.

    Hassan ME, Smith GW, Ott RS, et al. Reversibility of the reproductive toxicity of gossypol in peripubertal bulls. Theriogenology. 2004;61(6):1171-1179.

    Not in our library10.1016/j.theriogenology.2003.07.007

  53. 53.

    Gu Y, Anderson NO. Effects of gossypol on the estrous cycle and ovarian weight in the rat. Contraception. 1985;32(5):491-496.

    Not in our library10.1016/0010-7824(85)90019-8

  54. 54.

    Lin YC, Fukaya T, Rikihisa Y, Walton A. Gossypol in female fertility control: ovum implantation and early pregnancy inhibited in rats. Life Sciences. 1985;37(1):39-47.

    Not in our library10.1016/0024-3205(85)90623-x

  55. 55.

    Lagerlöf RK, Tone JN. The effect of gossypol acetic acid on female reproduction. Drug and Chemical Toxicology. 1985;8(6):469-482.

    Not in our library10.3109/01480548509041070

  56. 56.

    Gambill MD, Humphrey WD. Effects of diets containing gossypol on ovarian histology, function and fertility in prepubertal beef heifers. Theriogenology. 1993;40(3):585-593.

    Not in our library10.1016/0093-691x(93)90411-w

  57. 57.

    Randel RD, Willard ST, Wyse SJ, French LN. Effects of diets containing free gossypol on follicular development, embryo recovery and corpus luteum function in brangus heifers treated with bFSH. Theriogenology. 1996;45(5):911-922.

    Not in our library10.1016/0093-691x(96)00021-0

  58. 58.

    Arieli A. Whole cottonseed in dairy cattle feeding: a review. Animal Feed Science and Technology. 1998;72(1-2):97-110.

    Not in our library

  59. 59.

    Noftsger SM, Hopkins BA, Diaz DE, Brownie C, Whitlow LW. Effect of whole and expanded-expelled cottonseed on milk yield and blood gossypol. Journal of Dairy Science. 2000;83(11):2539-2547.

    Not in our library10.3168/jds.s0022-0302(00)75146-0

  60. 60.

    Shawrang P, Mansouri MH, Sadeghi AA, Ziaie F. Evaluation and comparison of gamma- and electron beam irradiation effects on total and free gossypol of cottonseed meal. Radiation Physics and Chemistry. 2011;80(6):761-762.

    Not in our library

  61. 61.

    Ebrahimi-Mahmoudabad SR, Taghinejad-Roudbaneh M. Investigation of electron beam irradiation effects on anti-nutritional factors, chemical composition and digestion kinetics of whole cottonseed, soybean and canola seeds. Radiation Physics and Chemistry. 2011;80(12):1441-1447.

    Not in our library

  62. 62.

    Lim S-J, Lee K-J. A microbial fermentation of soybean and cottonseed meal increases antioxidant activity and gossypol detoxification in diets for nile tilapia, oreochromis niloticus. Journal of the World Aquaculture Society. 2011;42(4):494-503.

    Not in our library

  63. 63.

    Zhang W-J, Xu Z-R, Sun J-Y, Yang X. Effect of selected fungi on the reduction of gossypol levels and nutritional value during solid substrate fermentation of cottonseed meal. Journal of Zhejiang University B: Science. 2006;7(9):690-695.

    Not in our library10.1631/jzus.2006.b0690

  64. 64.

    Zhang W-J, Xu Z-R, Zhao S-H, Sun J-Y, Yang X. Development of a microbial fermentation process for detoxification of gossypol in cottonseed meal. Animal Feed Science and Technology. 2007;135(1-2):176-186.

    Not in our library

  65. 65.

    Weng X-Y, Sun J-Y. Kinetics of biodegradation of free gossypol by Candida tropicalis in solid-state fermentation. Biochemical Engineering Journal. 2006;32(3):226-232.

    Not in our library

  66. 66.

    Zhang W-J, Xu Z-R, Zhao S-H, Jiang J-F, Wang Y-B, Yan X-H. Optimization of process parameters for reduction of gossypol levels in cottonseed meal by Candida tropicalis ZD-3 during solid substrate fermentation. Toxicon. 2006;48(2):221-226.

    Not in our library10.1016/j.toxicon.2006.05.003

  67. 67.

    Sun Z-T, Liu C, Du J-H. Optimisation of fermentation medium for the detoxification of free gossypol in cottonseed powder by Geotrichum candidum G07 in solid-state fermentation with response surface methodology. Annals of Microbiology. 2008;58(4):683-690.

    Not in our library

  68. 68.

    EL-Mokadem MY, Taha TA, Samak MA, Yassen AM. Alleviation of reproductive toxicity of gossypol using selenium supplementation in rams. Journal of Animal Science. 2012;90(9):3274-3285.

    Not in our library10.2527/jas.2011-4545

  69. 69.

    Velasquez-Pereira J, Chenoweth PJ, McDowell LR, et al. Reproductive effects of feeding gossypol and vitamin E to bulls. Journal of Animal Science. 1998;76(11):2894-2904.

    Not in our library10.2527/1998.76112894x

  70. 70.

    Velasquez-Pereira J, Aréchiga CF, McDowell LR, et al. Effects of gossypol from cottonseed meal and dietary vitamin E on the reproductive characteristics of superovulated beef heifers. Journal of Animal Science. 2002;80(9):2485-2492.

    Not in our library10.2527/2002.8092485x

  71. 71.

    Haschek WM, Beasley VR, Buck WB, Finnell JH. Cottonseed meal (gossypol) toxicosis in a swine herd. Journal of the American Veterinary Medical Association. 1989;195(5):613-615.

    Not in our library

  72. 72.

    Barraza ML, Coppock CE, Brooks KN, Wilks DL, Saunders RG, Latimer GW. Iron sulfate and feed pelleting to detoxify free gossypol in cottonseed diets for dairy cattle. Journal of Dairy Science. 1991;74(10):3457-3467.

    Not in our library10.3168/jds.s0022-0302(91)78536-6

  73. 73.

    Schneider IC, Ames ML, Rasmussen MA, Reilly PJ. Fermentation of cottonseed and other feedstuffs in cattle rumen fluid. Journal of Agricultural and Food Chemistry. 2002;50(8):2267-2273.

    Not in our library10.1021/jf010783n

  74. 74.

    Lindsey TO, Hawkins GE, Guthrie LD. Physiological responses of lactating cows to gossypol from cottonseed meal rations. Journal of Dairy Science. 1980;63(4):562-573.

    Not in our library10.3168/jds.s0022-0302(80)82972-9

  75. 75.

    Kim HL, Calhoun MC, Stipanovic RD. Accumulation of gossypol enantiomers in ovine tissues. Comparative Biochemistry and Physiology B: Biochemistry and Molecular Biology. 1996;113(2):417-420.

    Not in our library10.1016/0305-0491(95)02061-6

  76. 76.

    Abou-Donia MB, Othman MA, Obih P. Interspecies comparison of pharmacokinetic profile and bioavailability of (±)-gossypol in male Fischer-344 rats and male B6C3F mice. Toxicology. 1989;55(1-2):37-51.

    Not in our library10.1016/0300-483x(89)90173-x

  77. 77.

    Chen QQ, Chen H, Lei HP. Comparative study on the metabolism of optical gossypol in rats. Journal of Ethnopharmacology. 1987;20(1):31-37.

    Not in our library10.1016/0378-8741(87)90116-4

  78. 78.

    Eagle E. Effect of repeated doses of gossypol on the dog. Archives of Biochemistry. 1950;26(1):68-71.

    Not in our library

  79. 79.

    Patton CS, Legendre AM, Gompf RE, Walker MA. Heart failure caused by gossypol poisoning in two dogs. Journal of the American Veterinary Medical Association. 1985;187(6):625-627.

    Not in our library

  80. 80.

    Kerr LA. Gossypol toxicosis in cattle. Compendium on Continuing Education for the Practising Veterinarian. 1989;11(9):1139-1146.

    Not in our library

  81. 81.

    Gadelha ICN, do Nascimento Rangel AH, Silva AR, Soto-Blanco B. Efeitos do gossipol na reprodução animal. Acta Veterinaria Brasilica. 2011;5(2):129-135.

    Not in our library

  82. 82.

    Henry MH, Pesti GM, Brown TP. Pathology and histopathology of gossypol toxicity in broiler chicks. Avian Diseases. 2001;45(3):598-604.

    Not in our library

  83. 83.

    West JL. Lesions of gossypol poisoning in the dog. Journal of the American Veterinary Medical Association. 1940;96:74-76.

    Not in our library

  84. 84.

    Uzal FA, Puschner B, Tahara JM, Nordhausen RW. Gossypol toxicosis in a dog consequent to ingestion of cottonseed bedding. Journal of Veterinary Diagnostic Investigation. 2005;17(6):626-629.

    Not in our library10.1177/104063870501700622

  85. 85.

    Morgan S, Stair EL, Martin T, Edwards WC, Morgan GL. Clinical, clinicopathologic, pathologic, and toxicologic alterations associated with gossypol toxicosis in feeder lambs. American Journal of Veterinary Research. 1988;49(4):493-499.

    Not in our library

  86. 86.

    East NE, Anderson M, Lowenstine LJ. Apparent gossypol-induced toxicosis in adult dairy goats. Journal of the American Veterinary Medical Association. 1994;204(4):642-643.

    Not in our library

  87. 87.

    Zhang W-J, Xu Z-R, Pan X-L, Yan X-H, Wang Y-B. Advances in gossypol toxicity and processing effects of whole cottonseed in dairy cows feeding. Livestock Science. 2007;111(1-2):1-9.

    Not in our library

  88. 88.

    Willard ST, Neuendorff DA, Lewis AW, Randel RD. Effects of free gossypol in the diet of pregnant and postpartum Brahman cows on calf development and cow performance. Journal of Animal Science. 1995;73(2):496-507.

    Not in our library10.2527/1995.732496x

  89. 89.

    Rogers PAM, Henaghan TP, Wheeler B. Gossypol poisoning in young calves. Irish Veterinary Journal. 1975;29(1):9-13.

    Not in our library

  90. 90.

    Holmberg CA, Weaver LD, Gutterbock WM, Genes J, Montgomery P. Pathological and toxicological studies of calves fed a high concentration cotton seed meal diet. Veterinary Pathology. 1988;25(2):147-153.

    Not in our library10.1177/030098588802500207

  91. 91.

    Risco CA, Holmberg CA, Kutches A. Effect of graded concentrations of gossypol on calf performance: toxicological and pathological considerations. Journal of Dairy Science. 1992;75(10):2787-2798.

    Not in our library10.3168/jds.s0022-0302(92)78042-4

  92. 92.

    Zelski RZ, Rothwell JT, Moore RE, Kennedy DJ. Gossypol toxicity in preruminant calves. Australian Veterinary Journal. 1995;72(10):394-398.

    Not in our library10.1111/j.1751-0813.1995.tb06180.x

  93. 93.

    Fombad RB, Bryant MJ. An evaluation of the use of cottonseed cake in the diet of growing pigs. Tropical Animal Health and Production. 2004;36(3):295-305.

    Not in our library10.1023/b:trop.0000016828.48326.59

  94. 94.

    Hudson LM, Kerr LA, Maslin WR. Gossypol toxicosis in a herd of beef calves. Journal of the American Veterinary Medical Association. 1988;192(9):1303-1305.

    Not in our library

  95. 95.

    Mena H, Santos JEP, Huber JT, Tarazon M, Calhoun MC. The effects of varying gossypol intake from whole cottonseed and cottonseed meal on lactation and blood parameters in lactating dairy cows. Journal of Dairy Science. 2004;87(8):2506-2518.

    Not in our library10.3168/jds.s0022-0302(04)73375-5

  96. 96.

    Zbidah M, Lupescu A, Shaik N, Lang F. Gossypol-induced suicidal erythrocyte death. Toxicology. 2012;302(2-3):101-105.

    Not in our library10.1016/j.tox.2012.09.010

  97. 97.

    Tang F, Wong PYD. Serum potassium and aldosterone levels in gossypol-treated rats. International Journal of Andrology. 1984;7(2):149-153.

    Not in our library10.1111/j.1365-2605.1984.tb00770.x

  98. 98.

    Rikihisa Y, Lin YC. Effect of gossypol on the thyroid in young rats. Journal of Comparative Pathology. 1989;100(4):411-417.

    Not in our library10.1016/0021-9975(89)90006-6

  99. 99.

    Lin YC, Chitcharoenthum M, Rikihisa Y. Effect of gossypol on thyroid hormones in young female rats. Contraception. 1990;41(4):431-440.

    Not in our library10.1016/0010-7824(90)90042-t

  100. 100.

    Udoh P, Patil DR, Deshpande MK. Histopathological and biochemical effects of gossypol acetate on pituitary-gonadal axis of male albino rats. Contraception. 1992;45(5):493-509.

    Not in our library10.1016/0010-7824(92)90162-m

  101. 101.

    Janero DR, Burghardt B. Protection of rat myocardial phospholipid against peroxidative injury through superoxide-(xanthine oxidase)-dependent, iron-promoted fenton chemistry by the male contraceptive gossypol. Biochemical Pharmacology. 1988;37(17):3335-3342.

    Not in our library10.1016/0006-2952(88)90647-8

  102. 102.

    Fornes MW, Barbieri AM, Burgos MH. Sperm motility loss induced by gossypol: relation with OH. scavengers, motile stimulators and malondialdehyde production. Biochemical and Biophysical Research Communications. 1993;195(3):1289-1293.

    Not in our library10.1006/bbrc.1993.2183

  103. 103.

    de Peyster A, Quintanilha A, Packer L, Smith MT. Oxygen radical formation induced by gossypol in rat liver microsomes and human sperm. Biochemical and Biophysical Research Communications. 1984;118(2):573-579.

    Not in our library10.1016/0006-291x(84)91341-x

  104. 104.

    Kovaci P. Mechanism of drug and toxic actions of gossypol: focus on reactive oxygen species and electron transfer. Current Medicinal Chemistry. 2003;10(24):2711-2718.

    Not in our library10.2174/0929867033456369

  105. 105.

    Meksongsee LA, Clawson AJ, Smith FH. The in vivo effect of gossypol on cytochrome oxidase, succinoxidase, and succinic dehydrogenase in animal tissues. Journal of Agricultural and Food Chemistry. 1970;18(5):917-920.

    Not in our library10.1021/jf60171a043

  106. 106.

    Abou Donia MB, Dieckert JW. Gossypol: uncoupling of respiratory chain and oxidative phosphorylation. Life Sciences. 1974;14(10):1955-1963.

    Not in our library10.1016/0024-3205(74)90412-3

  107. 107.

    Tso WW, Lee CS. Gossypol uncoupling of respiratory chain and oxidative phosphorylation in ejaculated boar spermatozoa. Contraception. 1982;25(6):649-655.

    Not in our library10.1016/0010-7824(82)90066-x

  108. 108.

    Huang WM, Urthaler F. The direct negative inotropic effect of gossypol. Journal of Ethnopharmacology. 1986;17(1):31-36.

    Not in our library10.1016/0378-8741(86)90071-1

  109. 109.

    Wang Y, Lei H-P. Hepatotoxicity of gossypol in rats. Journal of Ethnopharmacology. 1987;20(1):53-64.

    Not in our library10.1016/0378-8741(87)90119-x

  110. 110.

    Manabe S, Nuber DC, Lin YC. Zone-specific hepatotoxicity of gossypol in perfused rat liver. Toxicon. 1991;29(6):787-790.

    Not in our library10.1016/0041-0101(91)90071-x

  111. 111.

    Qian SZ, Wang ZG. Gossypol: a potential antifertility agent for males. Annual Review of Pharmacology and Toxicology. 1984;24:329-360.

    Not in our library10.1146/annurev.pa.24.040184.001553

  112. 112.

    Yu Z-H, Chan HC. Gossypol as a male antifertility agent—why studies should have been continued. International Journal of Andrology. 1998;21(1):2-7.

    Not in our library10.1046/j.1365-2605.1998.00091.x

  113. 113.

    Coutinho EM. Gossypol: a contraceptive for men. Contraception. 2002;65(4):259-263.

    Not in our library10.1016/s0010-7824(02)00294-9

  114. 114.

    Dodou K. Investigations on gossypol: past and present developments. Expert Opinion on Investigational Drugs. 2005;14(11):1419-1434.

    Not in our library10.1517/13543784.14.11.1419

  115. 115.

    Chang Q, Liu Z, Ma W-Z, et al. Drug synergistic antifertility effect of combined administration of low-dose gossypol with steroid hormones in rats. Chinese Medical Journal. 2011;124(11):1678-1682.

    Not in our library

  116. 116.

    Chongthammakun S, Ekavipat C, Sanitwongse B, Pavasuthipaisit K. Effects of gossypol on human and monkey sperm motility in vitro. Contraception. 1986;34(3):323-331.

    Not in our library10.1016/0010-7824(86)90013-2

  117. 117.

    Hong CY, Huang JJ, Wu P. The inhibitory effect of gossypol on human sperm motility: relationship with time, temperature and concentration. Human Toxicology. 1989;8(1):49-51.

    Not in our library10.1177/096032718900800109

  118. 118.

    Brocas C, Rivera RM, Paula-Lopes FF, et al. Deleterious actions of gossypol on bovine spermatozoa, oocytes, and embryos. Biology of Reproduction. 1997;57(4):901-907.

    Not in our library10.1095/biolreprod57.4.901

  119. 119.

    Chenoweth PJ, Chase CC, Risco CA, Larsen RE. Characterization of gossypol-induced sperm abnormalities in bulls. Theriogenology. 2000;53(5):1193-1203.

    Not in our library10.1016/s0093-691x(00)00264-8

  120. 120.

    Yuan YY, Shi QX. Inhibition of hamster sperm acrosomal enzyme by gossypol is closely associated with the decrease in fertilization capacity. Contraception. 2000;62(4):203-209.

    Not in our library10.1016/s0010-7824(00)00161-x

  121. 121.

    Beaudoin AR. A developmental toxicity evaluation of gossypol. Contraception. 1988;37(2):197-219.

    Not in our library10.1016/0010-7824(88)90131-x

  122. 122.

    Nunes FDCR, de Araujo DAFV, Bezerra MB, Soto-Blanco B. Effects of gossypol present in cottonseed cake on the spermatogenesis of goats. Journal of Animal and Veterinary Advances. 2010;9(1):75-78.

    Not in our library

  123. 123.

    Guedes FCB, Soto-Blanco B. Sperm quality of sheep fed cottonseed cake. Acta Scientiae Veterinariae. 2010;38(4):415-418.

    Not in our library

  124. 124.

    Ueno H, Sahni MK, Segal SJ, Koide SS. Interaction of gossypol with sperm macromolecules and enzymes. Contraception. 1988;37(3):333-341.

    Not in our library10.1016/0010-7824(88)90033-9

  125. 125.

    Teng CS. Reversible changes in the content of cellular and microtubular tubulin in spermatogenic cells after gossypol treatment. Contraception. 1997;55(1):41-46.

    Not in our library10.1016/s0010-7824(96)00240-5

  126. 126.

    Breitbart H, Rubinstein S, Nass-Arden L. Effect of gossypol-acetic acid on calcium transport and ATPase activity in plasma membranes from ram and bull spermatozoa. International Journal of Andrology. 1984;7(5):439-447.

    Not in our library10.1111/j.1365-2605.1984.tb00801.x

  127. 127.

    Breitbart H, Mayevsky A, Nass-Arden L. Molecular mechanisms of gossypol action on sperm motility. International Journal of Biochemistry. 1989;21(10):1097-1102.

    Not in our library10.1016/0020-711x(89)90049-9

  128. 128.

    Hoffer AP. Effects of gossypol on the seminiferous epithelium in the rat: a light and electron microscope study. Biology of Reproduction. 1983;28(4):1007-1020.

    Not in our library10.1095/biolreprod28.4.1007

  129. 129.

    Arshami J, Ruttle JL. Effects of diets containing gossypol on spermatogenic tissues of young bulls. Theriogenology. 1988;30(3):507-516.

    Not in our library10.1016/0093-691x(88)90200-2

  130. 130.

    Romualdo GS, Klinefelter GR, de Grava Kempinas W. Postweaning exposure to gossypol results in epididymis-specific effects throughout puberty and adulthood in rats. Journal of Andrology. 2002;23(2):220-228.

    Not in our library

  131. 131.

    Zhang M, Yuan H, He Z, et al. DNA damage and decrease of cellular oxidase activity in piglet sertoli cells exposed to gossypol. African Journal of Biotechnology. 2011;10(14):2797-2802.

    Not in our library10.1292/jvms.10-0236

  132. 132.

    Timurkaan N, Yilmaz F, Timurkaan S. Effects of cottonseed flour on immunohistochemical localization of androgen receptors (AR) in rat testes. Revue de Medecine Veterinaire. 2011;162(1):13-17.

    Not in our library

  133. 133.

    Gray ML, Greene LW, Williams GL. Effects of dietary gossypol consumption on metabolic homeostasis and reproductive endocrine function in beef heifers and cows. Journal of Animal Science. 1993;71(11):3052-3059.

    Not in our library10.2527/1993.71113052x

  134. 134.

    Adeyemo GO, Longe OG, Adejumo DO. The reproductive performance of breeder cocks fed cottonseed cake-based diets. International Journal of Poultry Science. 2007;6(2):140-144.

    Not in our library

  135. 135.

    Basini G, Bussolati S, Baioni L, Grasselli F. Gossypol, a polyphenolic aldehyde from cotton plant, interferes with swine granulosa cell function. Domestic Animal Endocrinology. 2009;37(1):30-36.

    Not in our library10.1016/j.domaniend.2009.01.005

  136. 136.

    Gu Y, Lin YC, Rikihisa Y. Inhibitory effect of gossypol on steroidogenic pathways in cultured bovine luteal cells. Biochemical and Biophysical Research Communications. 1990;169(2):455-461.

    Not in our library10.1016/0006-291x(90)90353-o

  137. 137.

    Lin YC, Coskun S, Sanbuissho A. Effects of gossypol on in vitro bovine oocyte maturation and steroidogenesis in bovine granulosa cells. Theriogenology. 1994;41(8):1601-1611.

    Not in our library

  138. 138.

    Zirkle SM, Lin YC, Gwazdauskas FC, Canseco RS. Effect of gossypol on bovine embryo development during the preimplantation period. Theriogenology. 1988;30(3):575-582.

    Not in our library10.1016/0093-691x(88)90207-5

  139. 139.

    Lin YC, Rajamahendran P, Rikihisa Y. Inhibition of rat embryo implantation in the gossypol-treated uterine horn. Theriogenology. 1991;35(4):769-777.

    Not in our library10.1016/0093-691x(91)90418-d

  140. 140.

    Hernández-Cerón J, Jousan FD, Soto P, Hansen PJ. Timing of inhibitory actions of gossypol on cultured bovine embryos. Journal of Dairy Science. 2005;88(3):922-928.

    Not in our library10.3168/jds.s0022-0302(05)72759-4

  141. 141.

    Villaseñor M, Coscioni AC, Galvão KN, Chebel RC, Santos JEP. Gossypol disrupts embryo development in heifers. Journal of Dairy Science. 2008;91(8):3015-3024.

    Not in our library10.3168/jds.2007-0939

  142. 142.

    Lin YC, Sanbuissho A, Coskun S, Rikihisa Y. Inhibition of in vitro fertilization and early embryonic development in hamsters by gossypol. Life Sciences. 1994;55(14):1139-1145.

    Not in our library10.1016/0024-3205(94)00242-8

  143. 143.

    Li YF, Booth GM, Seegmiller RE. Evidence for embryotoxicity of gossypol in mice and chicks with no evidence of mutagenic activity in the ames test. Reproductive Toxicology. 1989;3(1):59-62.

    Not in our library10.1016/0890-6238(89)90039-7

  144. 144.

    Sein GM. The embryotoxic and immunodepressive effects of gossypol. American Journal of Chinese Medicine. 1986;14(3-4):110-115.

    Not in our library10.1142/s0192415x8600017x

  145. 145.

    Morales H, Tilquin P, Rees JF, Massip A, Dessy F, van Langendonckt A. Pyruvate prevents peroxide-induced injury of in vitro preimplantation bovine embryos. Molecular Reproduction and Development. 1999;52(2):149-157.

    Not in our library10.1002/(sici)1098-2795(199902)52:2<149::aid-mrd5>3.0.co;2-4

  146. 146.

    Hervé J-C, Pluciennik F, Bastide B, et al. Contraceptive gossypol blocks cell-to-cell communication in human and rat cells. European Journal of Pharmacology. 1996;313(3):243-255.

    Not in our library10.1016/0014-2999(96)00476-1

  147. 147.

    Yurtcu E, Ergun MA, Menevse A. Apoptotic effect of gossypol on human lymphocytes. Cell Biology International. 2003;27(9):791-794.

    Not in our library10.1016/s1065-6995(03)00168-9

  148. 148.

    Cui G-H, Xu Z-L, Yang Z-J, Xu Y-Y, Xue S-P. A combined regimen of gossypol plus methyltestosterone and ethinylestradiol as a contraceptive induces germ cell apoptosis and expression of its related genes in rats. Contraception. 2004;70(4):335-342.

    Not in our library10.1016/j.contraception.2004.02.020

  149. 149.

    Ergun MA, Konac E, Erbas D, Ekmekci A. Apoptosis and nitric oxide release induced by thalidomide, gossypol and dexamethasone in cultured human chronic myelogenous leukemic K-562 cells. Cell Biology International. 2004;28(3):237-242.

    Not in our library10.1016/j.cellbi.2003.12.005

  150. 150.

    Moon D-O, Kim M-O, Lee J-D, Kim G-Y. Gossypol suppresses NF-κB activity and NF-κB-related gene expression in human leukemia U937 cells. Cancer Letters. 2008;264(2):192-200.

    Not in our library10.1016/j.canlet.2008.01.030

  151. 151.

    Cengiz E, Karaca B, Kucukzeybek Y, et al. Overcoming drug resistance in hormone-and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination. Molecular Biology Reports. 2010;37(3):1269-1277.

    Not in our library10.1007/s11033-009-9501-y

  152. 152.

    Moon D-O, Choi YH, Moon S-K, Kim W-J, Kim G-Y. Gossypol decreases tumor necrosis factor-α-induced intercellular adhesion molecule-1 expression via suppression of NF-κB activity. Food and Chemical Toxicology. 2011;49(4):999-1005.

    Not in our library10.1016/j.fct.2011.01.006

  153. 153.

    Cheng J-S, Lo Y-K, Yeh J-H, et al. Effect of gossypol on intracellular Ca2+ regulation in human hepatoma cells. Chinese Journal of Physiology. 2003;46(3):117-122.

    Not in our library

  154. 154.

    Braga AP, MacIel MV, Guerra DGF, Maia ISAS, Oloris SCS, Soto-Blanco B. Extruded-expelled cottonseed meal decreases lymphocyte counts in male sheep. Revue de Medecine Veterinaire. 2012;163(3):147-152.

    Not in our library

  155. 155.

    Xu W-B, Xu L-H, Lu H-S, et al. The immunosuppressive effect of gossypol in mice is mediated by inhibition of lymphocyte proliferation and by induction of cell apoptosis. Acta Pharmacologica Sinica. 2009;30(5):597-604.

    Not in our library10.1038/aps.2009.35

  156. 156.

    Quintana PJE, de Peyster A, Klatzke S, Park HJ. Gossypol-induced DNA breaks in rat lymphocytes are secondary to cytotoxicity. Toxicology Letters. 2000;117(1-2):85-94.

    Not in our library10.1016/s0378-4274(00)00244-7

  157. 157.

    Sijun D, Pawlak A, Poźniak B, et al. Effects of gossypol acetic acid on cellular and humoral immune response in non-immunized and SRBC-immunized mice. Central-European Journal of Immunology. 2012;37(1):11-19.

    Not in our library

  158. 158.

    Xu D, Cai W-J, Zhu B-H, Dong C-J, Zheng Z-C, Gao Z-Q. Clinical safety of long-term administration of gossypol in 32 cases. Contraception. 1988;37(2):129-135.

    Not in our library10.1016/0010-7824(88)90123-0

  159. 159.

    Nagalakshmi D, Sastry VRB, Agrawal DK, Katiyar RC. Haematological and immunological response in lambs fed on raw and variously processed cottonseed meal. Asian-Australasian Journal of Animal Sciences. 2001;14(1):21-29.

    Not in our library

  160. 160.

    Pattanaik AK, Sastry VRB, Singh DK, Goswami TK, Mohanty DN. Effect of gossypol from cottonseed meal diets on some clinico-biochemical parameters and humoral immune response of crossbred calves fed barley or sorghum. Asian-Australasian Journal of Animal Sciences. 2003;16(9):1291-1296.

    Not in our library

  161. 161.

    Ohuchi K, Watanabe M, Hirasawa N, Tsurufuji S, Ozeki T, Fujiki H. Inhibition by gossypol of tumor promoter-induced arachidonic acid metabolism in rat peritoneal macrophages. Biochimica et Biophysica Acta: Molecular Cell Research. 1988;971(1):85-91.

    Not in our library10.1016/0167-4889(88)90164-4

  162. 162.

    Barros MM, Lim C, Klesius PH. Effect of soybean meal replacement by cottonseed meal and iron supplementation on growth, immune response and resistance of channel catfish (Ictalurus puctatus) to Edwardsiella ictaluri challenge. Aquaculture. 2002;207(3-4):263-279.

    Not in our library

  163. 163.

    Yildirim M, Lim C, Wan PJ, Klesius PH. Growth performance and immune response of channel catfish (Ictalurus puctatus) fed diets containing graded levels of gossypol-acetic acid. Aquaculture. 2003;219(1–4):751-768.

    Not in our library

  164. 164.

    Fisher GS, Frank AW, Cherry JP. Total gossypol content of glandless cottonseed. Journal of Agricultural and Food Chemistry. 1988;36(1):42-44.

    Not in our library

  165. 165.

    Broderick GA, Craig WM. Effect of heat treatment on ruminal degradation and escape, and intestinal digestibility of cottonseed meal protein. Journal of Nutrition. 1980;110(12):2381-2389.

    Not in our library10.1093/jn/110.12.2381

  166. 166.

    Henry MH, Pesti GM, Bakalli R, et al. The performance of broiler chicks fed diets containing extruded cottonseed meal supplemented with lysine. Poultry Science. 2001;80(6):762-768.

    Not in our library10.1093/ps/80.6.762

  167. 167.

    Jaddou H, Al Hakim M, Al Adamy LZ, Mhaisen MT. Effect of gamma-radiation on gossypol in cottonseed meal. Journal of Food Science. 1983;48(3):988-989.

    Not in our library

  168. 168.

    Jo C, Yook HS, Lee MS, et al. Irradiation effects on embryotoxicity and oxidative properties of gossypol dissolved in methanol. Food and Chemical Toxicology. 2003;41(10):1329-1336.

    Not in our library10.1016/s0278-6915(03)00125-x

  169. 169.

    Smalley SA, Bicknell EJ. Gossypol toxicity in dairy cattle. Compendium on Continuing Education for the Practising Veterinarian. 1982;4(9):S378-S381.

    Not in our library

  170. 170.

    Yang X, Sun J-Y, Guo J-L, Weng X-Y. Identification and proteomic analysis of a novel gossypol-degrading fungal strain. Journal of the Science of Food and Agriculture. 2012;92(4):943-951.

    Not in our library10.1002/jsfa.4675

  171. 171.

    Sun H, Tang JW, Fang CL, et al. Molecular analysis of intestinal bacterial microbiota of broiler chickens fed diets containing fermented cottonseed meal. Poultry Science. 2013;92(2):392-401.

    Not in our library10.3382/ps.2012-02533

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