Effects Of Gossypol Acetic Acid Research Articles

Effects of gossypol on the antioxidant defense system of the rat testis.

This study examined the effects of gossypol acetic acid on the antioxidant defense system of the rat testis. In gossypol-treated animals testis catalase and glutathione peroxidase activities were decreased. Catalase and glutathione peroxidase are the two enzymes that protect against oxidative damage by hydrogen peroxide. Other antioxidants that were reduced in treated animals were glucose-6-phosphate dehydrogenase, superoxide dismutase, glutathione reductase, alpha-tocopherol, and ascorbate. Gossypol, a pigment of cottonseed and cottonseed products, causes infertility in humans and many animal species, but its mechanism of action is unknown. Gossypol is known to produce reactive oxygen species in vitro. Oxidative injury caused by the generation of reactive oxygen species and a compromised antioxidant defense system may be responsible for the antifertility effects of gossypol.

The Effects of Gossypol on Spermatogenesis and Development of the Eyefluke, Philophthalmus gralli, and Its Chicken Host

To determine the effects of gossypol, a male antifertility drug, on the eyefluke, P. gralli, this chemical was administered orally to chickens in long-term and short-term regimens. Gossypol acetic acid (GAA), fed to juvenile chickens from 1 to 35 days, caused a decreased weight gain when compared to controls on untreated feed. An FeSO4 supplement to the GAA-fed chickens provided partial protection from the toxic effects of GAA. Worms from GAA-fed chickens were significantly larger than controls, while those from chickens fed GAA + FeSO4 were intermediate in size. Sperm development in these worms was unaffected by GAA. In a second experiment, GAA was administered either in the feed of the hosts from days 35 to 70 or by capsule from days 63 to 77. Worms were exposed to [3H] thymidine, transplanted to the host's eyes, removed on a timed schedule, and processed for autoradiography to determine the rate of spermatogenesis in both GAA-feed and GAA-capsule groups. Early stages of spermatogenesis in both groups were unaffected by GAA and later stages developed at a slightly faster rate than reported for worms from chickens on untreated feed. Higher frequencies of testicular anomalies were observed in both groups including 3 testes, 1 testis, no testes, fused testes, degenerating testes, ovarian tissue in the testes, deformed sperm, and encapsulated sperm. Testes from chickens in both groups showed a significantly lower weight and no signs of spermatogenesis when compared to control chickens.

Effects of gossypol acetic acid on rat luteal cells in vitro

The action of gossypol acetic acid (GAA) on 125I-hCG binding, gonadotropin-stimulated cAMP accumulation and progesterone production was investigated utilizing rat ovaries. Incubation of luteal cells for 3 h with increasing concentration of GAA caused a significant inhibition of gonadotropin-stimulated steroidogenesis. The inhibitory effect of GAA was concentration dependent. GAA at concentrations of 10–30 μg/ml reduced cAMP formation in response to hCG. It was shown that the activity of adenylate cyclase of luteal cells was inhibited by 10 μg/ml GAA. GAA at a concentration of 30 μg/ml was found to have an inhibitory effect on 8Br-cAMP-stimulated progesterone production. GAA did not affect 125I-hCG binding to LH receptor on the luteal cell surface. These results suggest that in luteal cells GAA inhibits steroidogenesis at the step of gonadotropin-stimulated cAMP formation. Adenylate cyclase of luteal cells was inhibited.

Effect of gossypol acetic acid on the epididymis: Histochemical and scanning electron microscope studies

Rats were treated orally with gossypol acetic acid at 30 or 10 mg/kg daily, 6 days a week, for 8, 12, 14 or 16 weeks. At the end of each treatment regimen, treated rats and an equal number of control rats were killed for histological and histochemical studies. From 8 weeks onward, as a result of the treatment, the tubular lumen of the corpus epididymides became narrowed with thickened pseudostratified epithelium and there was a reduction in the amount of spermatozoa. There was an increase in esterase, alkaline phosphatase, acid phosphatase and ATPase activity. These changes increased in intensity with the duration of treatment. Scanning electron microscopic examinations of the corpus epididymides of rats treated for 16 weeks, compared with those of controls, revealed similar changes, namely, narrowing of the tubular lumen, thickening of the pseudostratified epithelium and reduction in the number of spermatozoa.

Effects of gossypol on human and monkey sperm motility [formula omitted

The effects of gossypol acetic acid on human and monkey sperm motility in vitro were studied by using multiexposure photography technique. Human and monkey spermatozoa were inhibited by gossypol to different degrees. Monkey sperm were absolutely immotile within 15 min after 50 μM of gossypol was added, but motility of human spermatozoa was not completely suppressed by gossypol even at the highest concentration used and longest duration of exposure.

The effect of gossypol acetic acid on female reproduction.

The effects of gossypol acetic acid (GAA) on various aspects of female rat reproduction were evaluated. Forty sexually mature, nulliparous female Holtzman rats received a daily, oral dose of GAA (20 mg GAA/Kg body wt) for 60 days. Nineteen control animals were utilized. Throughout the treatment period, GAA treated rats had significantly more irregular estrous cycles than did controls, and the mean duration of an estrous cycle in the GAA rats was significantly longer than that of controls. A significantly lower body weight gain was observed in all GAA treated animals. A prolonged time for mating, a decrease in incidence of pregnancy, and a reduction in number of viable embryos at Day 13 of gestation were noted among GAA treated animals. Weaning weights of offspring from GAA dams were significantly less than weaning weights of offspring from control dams.

Effect of gossypol-acetic acid on calcium transport and ATPase activity in plasma membranes from ram and bull spermatozoa.

The effects of gossypol acetic acid on the activity of Mg-ATPase and Ca-Mg-ATPase and on calcium uptake by plasma membranes from ram and bull spermatozoa were examined. The three parameters were almost completely inhibited by 10 microM gossypol for both ram and bull sperm. In order to assess the effects of higher gossypol concentrations isolated membrane vesicles were loaded with calcium by operating the ATP-dependent calcium pump after which gossypol was added and calcium uptake followed. At 10 microM gossypol, additional calcium uptake was 85% inhibited while at 40 microM a release of the accumulated calcium was observed. The inhibitory effect of 10 microM gossypol was almost completely reversible by simple dilution of gossypol-treated membranes, whilst at 40 microM the effect was only 50% reversible. The data show a high degree of similarity between bull and ram, suggesting minimal differences between the two species as far as the structure and function of the sperm plasma membrane is concerned.

Effect of the antifertility agent, gossypol acetic acid, on the metabolism and testosterone secretion of isolated rat interstitial cells in vitro

Gossypol acetic acid is a polyphenolic compound present in the seed of cotton plants. Its antifertility activity by inhibition of spermatogenesis was proven in a large group of animals, including man. In the present study, the direct effect of gossypol acetic acid on collagenase isolated rat I-cells (interstitial cells) was investigated. It was shown that gossypol acetic acid depressed significantly the metabolic rate of the cells. Glucose utilization was abolished by a starting dose of 100 μg/ml. Oxygen consumption of I-cells was reduced even at a smaller dose of gossypol (50 μg/ml). At these doses, the vitality of the cells remained (proven by trypan blue exclusion test). slightly 3 β-Hydroxysteroid dehydrogenase (3 β-HSD) histochemical stain was decreased. Increasing doses of gossypol caused a marked decrease in the vitality of I-cells and a dramatic drop in histochemical stain for 3 β-HSD. The pH of the medium was not changed at any dose of treatment. In cultures of I-cells not stimulated by hCG, gossypol did not affect the tonic slow release of testosterone. Thus, gossypol acetic acid has a direct inhibitory effect on isolated rat I-cells, depressing cell metabolism. The failure of some of the other groups to show such an effect, especially in vivo, can be attributed to differences in the dose of treatment and strain of animals.

Effects of Gossypol Acetic Acid on the Activity of LDH-C4 From Human and Rabbit Spermatozoa

Effects of Gossypol Acetic Acid on the Activity of LDH-C4 From Human and Rabbit Spermatozoa

Effects of gossypol acetic acid on the activity of LDH‐C4 from human and rabbit spermatozoa

This report focuses on the effect of gossypol acetic acid on LDH-C4 from human and rabbit spermatozoa. Human semen was obtained by masturbation after 3-5 days of abstinence. Semen from successfully vasectomized healthy men was used for studies on the LDH isoenzymes other than LDH-C4 in seminal plasma. Rabbit semen was collected by an artificial vagina. Human samples containing less than 100 million spermatozoa/ml were pooled to obtain a sufficient number of spermatozoa. Rabbit samples were not pooled. LDH activity was analyzed spectrophotometrically. Gossypol acetic acid was obtained from the Special Program of Research on Human Reproduction, World Health Organization, Switzerland through their collaboration with the National Institute of Health in the US and was dissolved in ethanol. Freshly prepared solutions were used for each experiment and 20 mcl added to the cuvette. LDH-C4 from human spermatozoa was inhibited by GAA in a dose dependent manner, with 50% inhibition noted between 50-75 mcm. LDH-C4 from rabbit spermatozoa was slightly less sensitive to GAA as 50% inhibition was observed at concentrations between 75-100 mcm. The interindividual differences in sensitivity to GAA was small in human samples but in the experiment with rabbit semen the interindividual and the intraindividual differences were great. The total LDH activity in seminal plasma from both human (normal and vasectomized men) and rabbit was insensitive to GAA but a minor inhibition was sometimes noted at 100 mcm. It has been proposed that inhibition of LDH-C4 in the testis and/or in ejaculated spermatozoa could provide a possible explanation for the antifertility effect of gossypol. Gossypol has been reported to be much less effective as a male contraceptive in the rabbit than in man. In this study gossypol was slightly less active as an inhibitor of sperm LDH-C4 from rabbits than from humans. This could indicate that an effect by gossypol on sperm LDH-C4 activity is not a major mode of action for its antifertility action. The mode of action of gossypol is most likely complex, involving a number of essential enzyme systems.

Hypolipidemic effects of gossypol in cynomolgus monkeys (Macaca fascicularis).

The effect of gossypol acetic acid (gossypol) on plasma lipid concentrations was studied in adult male cynomolgus monkeys consuming a diet containing 0.19 mg cholesterol/Kcal. Gossypol was administered orally at 5 (n = 4) or 10 (n = 3) mg/kg/day for 6 months. A significant decrease in total plasma cholesterol (TPC) and low density lipoprotein and very low density lipoprotein-cholesterol (LDL + VLDL-chol) concentrations was observed without any significant decrease in plasma high density lipoprotein-cholesterol (HDL-chol) levels among 10 mg/kg/day gossypol-treated animals. This is a new therapeutic property of gossypol that has been previously reported. No appreciable differences were observed in plasma levels of TPC and LDL + VLDL-chol among 5 mg/kg/day gossypol-treated animals when compared to controls until the gossypol dosage was increased to 10 mg/kg/day, thus suggesting that hypolipidemic effect of gossypol is dose-dependent. In general, no adverse clinicopathological findings were noted except a temporary diarrhea and loss of appetite among 10 mg/kg/day gossypol-treated animals during the initial stages of treatment. In conclusion, it is tempting to speculate that gossypol might possibly reduce the intestinal absorption of dietary cholesterol or it may reduce the hepatic synthesis of low density lipoproteins. These results also suggest that gossypol may be a particularly useful drug in lowering plasma cholesterol concentrations in addition to its previously demonstrated antifertility properties in males.

Cottonseed oil as a vaginal contraceptive.

The effect of gossypol acetic acid an cottonseed oil emulsion on human spermatozoal motility was tested. Contrary to a recent report [Waller et al. (1980): Contraception 22:183-187] that gossypol acetic acid is harmless to human spermatozoal motility in vitro, 10-3 M gossypol acetic acid completely abolished spermatozoal motility. This discrepancy might have stemmed from an oversight in the gossypol solubility. Cottonseed oil emulsion also exhibited spermatozoal motility inhibition. The applicability of this natural low toxicity cottonseed oil as vaginal contraceptive was explored