[Isolation of (-)-gossypol from natural plant].
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Biomedical subjects
Publications and source records attributed to R H Zhou.
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Gossypol, a human antifertility agent isolated from the cotton plant, was found to induce a dose-dependent increase in the frequency of DNA-strand breaks in human leukocytes exposed to 2-40 micrograms/ml of the drug for 1 h in serum-free medium in vitro. DNA-strand breaks were studied by alkaline elution or alkaline unwinding of DNA followed by hydroxylapatite-chromatography. No decrease of gossypol-induced DNA-strand breaks was observed after post-treatment incubation times up to 24 h, whereas X-ray-induced DNA breaks disappeared within 2 h under the same incubation conditions. Cells exposed to gossypol in the presence of 10% fetal calf serum showed no or little increase of DNA breaks, suggesting that serum proteins inhibit the DNA-damaging activity of the drug. Both optical isomers of gossypol induced DNA-strand breaks. However, the effect of (-)-gossypol was only about half of that of (+)-gossypol and the racemic form. The induction and persistence of DNA-strand breaks by gossypol, as well as the reduction of this effect in the presence of serum should be considered in the evaluation of the potential in vivo genotoxicity of the drug.
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Racemic (+/-) mixtures of gossypol isomers exert an antifertility effect by inhibiting sperm motility and spermatogenesis. Purified (+) gossypol has been shown to be without these actions. In this study pure preparations of both (+) and (-) gossypol were found to inhibit, in a similar manner, both basal and LH-stimulated release of testosterone by isolated Leydig cells at concentrations down to 21 microM. It is possible that use of low doses of pure (-) gossypol could inhibit fertility with less endocrine side effects.
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An endemic disease was discovered in 1961 in parts of the population of Enshi County, Hubei Province of the People's Republic of China. During the years of the highest prevalence, from 1961 to 1964, the morbidity was almost 50% in the 248 inhabitants of the five most heavily affected villages; its cause was determined to be selenium intoxication. The most common sign of the poisoning was loss of hair and nails. In areas of high incidence, lesions of the skin, nervous system, and possibly teeth may have been involved. A case is reported of a middle-aged, female hemiplegic, whose illness and death apparently were related to selenosis. Daily dietary intakes of selenium, estimated after the peak prevalence had subsided, averaged 4.99 (range 3.20 to 6.69) mg and hair and blood selenium levels averaged 32.2 and 3.2 micrograms/ml, respectively. Up to 1000x differences occurred when selenium contents of vegetables, cereals, scalp hair, blood, and urine from the selenosis areas were compared with those from Keshan disease (selenium deficiency) areas. The ultimate environmental source of selenium was a stony coal of very high selenium content (average more than 300 micrograms/g; one sample exceeded 80,000 micrograms/g). Selenium from the coal entered the soil by weathering and was available for uptake by crops because of the traditional use of lime as fertilizer in that region. This particular outbreak of human selenosis was due to a drought that caused failure of the rice crop, forcing the villagers to eat more high-selenium vegetables and maize and fewer protein foods.