Gossypol toxicity studies

Jaroszewski, J. W., Kaplan, O., and Cohen, J. S. (1990). Action of gossypol and rhodamine 123 on wild type and multidrug-resistant MCF-7 human breast cancer cells 31P nuclear magnetic resonance and toxicity studies. Cancer Res. 50, 6936-6943. 

Since feeds contain other substances than those required by the animals of interest, studies have also been conducted on antinutritional factors in feedstuffs and on the use of additives. Certain feed ingredients contain chemicals that retard growth or may actually be toxic. Examples are gossypol in cottonseed meal and trypsin inhibitor in soybean meal. Restriction on the amount of the feedstuffs used is one way to avoid problems. In some cases, as is tme of trypsin inhibitor, proper processing can destroy the antinutritional factor. In this case, heating of soybean meal is effective. 

Gossypol is a racemic mixture of (+)-gossypol and (—)-gossypol. When tested separately in male rats in a dosage of 30 mg/kg orally for 14 days, only the latter enantiomer had a clear anti-fertility effect. Furthermore, (j-)-gossypol has less acute toxicity than (-)-gossypol after intraperito-neal administration to mice. In a human study, the enantiomers showed pharmacokinetic differences in half-life less than 5 hours for (-)-gossypol compared with 133 hours for the (+)-enantiomer. 

Gossypol is a polyphenolic aldehydic compound, and it has been studied for its versatile biological activities. Gossypol s biological activities are based on direct chemical reactions, the inhibition of enzymes, and the regulation of signal transduction pathways. However, due to its toxicity, the application of gossypol is sometimes limited. 

Clark, E. P. (1927). Studies on gossypol. 1. The preparation, purification, and some of the properties of gossypol, the toxic principle of cottonseed. /. Biol. Chem. 75, 725-739. 

Cotton and Levant cotton root barks have traditionally been used as abortifacients (Conway and Slocumb 1979 Felter and Lloyd 1898 Moore 1978). A number of animal studies have indicated that the compound gossypol has embryo-toxic activity, while other studies have indicated no such activity and a lack of teratogenic effects (Li et al. 1989 Qian and Wang 1984 Randel et al. 1992 Sein 1986 Lin et al. 1985). Based on this information, use during pregnancy is not recommended except under the supervision of a qualified healthcare practitioner. 

A reproductive toxicity review indicated that animal studies of the compound gossypol demonstrated no teratogenic activity or abortifacient activity of the compound (Randel et al. 1992). No teratogenicity or embryotoxicity of gossypol was reported in studies with rats and rabbits at 5 to 30 times the clinical dose (Qian and Wang 1984). No teratogenic effects were observed in rats orally administered 40 mg/kg of gossypol (Beaudoin 1985). 

Only (-)-gossypol is toxic, and only for omnivores. Chronic intoxication causedby low, long-term income is reflected in reduced appetite, liver damage and reduced blood clotting, and a reversible sterility in males at a dose of about 10 mg per day. In addition to these effects, gossypol has some activity as an anti-malarial drug and is studied for its anticarcinogenic properties. 

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