Chronic chromium exposure-induced changes in testicular histoarchitecture are associated with oxidative stress: study in a non-human primate (Macaca radiata Geoffroy).

BACKGROUND: Reproductive toxicity of chromium is in dispute despite positive findings in rodents. Recently we reported epididymal toxicity of hexavalent chromium (CrVI) in bonnet monkeys and in this paper we report its testicular toxicity. METHODS: Adult monkeys (Macaca radiata) were given drinking water containing CrVI (100, 200, 400 p.p.m.) for 6 months and testes were removed for ultrastructural and biochemical analyses. RESULTS: CrVI treatment disrupted spermatogenesis, leading to accumulation of prematurely released spermatocytes, spermatids and uni- and multinucleate giant cells in the lumen of seminiferous tubules. Transmission electron microscopy revealed granulation of chromatin and vacuolation between acrosomal cap and manchette microtubules of elongated spermatids and in the Golgi area of round spermatids. Pachytene spermatocytes had fragmented chromatin and swollen mitochondria with collapsed cristae. Spermatocytes and spermatogonia in the basal compartment were unaffected. Macrophages containing phagocytosed sperm and dense inclusions in Sertoli cells were seen. Specific activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase and concentrations of the non-enzymatic antioxidants glutathione, vitamins A, C and E decreased, while concentrations of H(2)O(2) and hydroxyl radicals increased in the testis of chromium-treated monkeys. Withdrawal of chromium treatment for 6 months normalized spermatogenesis and the status of pro- and antioxidants in the testis. CONCLUSIONS: CrVI disrupts spermatogenesis by inducing free radical toxicity, and supplementation of antioxidant vitamins may be beneficial to the affected subjects.

Retention of cytoplasmic droplet by rat cauda epididymal spermatozoa after treatment with cytotoxic and xenobiotic agents.

Spermatozoa leaving the testis contain a cytoplasmic droplet which they release during transit through the epididymis before reaching the cauda epididymidis. The cytoplasmic droplet shows P450 aromatase activity, which plays a role in synthesis of oestrogen from androgen. In the present study, 3-month-old Wistar strain male albino rats were administered with the organophosphate insecticides malathion or dichlorvos, or the phytotherapeutics andrographolide or ursolic acid. Segments of the epididymis were subjected to histopathological and ultrastructural analyses and it was found that 60-95% of the spermatozoa residing in the lumen of the cauda epididymidis retained the cytoplasmic droplet. The motility of the spermatozoa released from the cauda epididymidis was inhibited. One of the mechanisms of action of these toxicants on male reproductive function may be attributed to the retention of the cytoplasmic droplet and the resultant impairment of sperm motility.

Aspects of the male reproductive toxicity/male antifertility property of andrographolide in albino rats: effect on the testis and the cauda epididymidal spermatozoa.

Previous work has shown that Andrographis paniculata leaf, when fed to male albino rats, causes the arrest of spermatogenesis. The present study was undertaken to investigate whether andrographolide, one of the major constituents of this plant, is responsible for such an effect. The compound was administered to 3-month-old male Wistar albino rats at two dose levels, for 48 days. Fertility tests, analysis of the counts, motility and abnormalities of the cauda epididymidal spermatozoa, and histopathological-evaluation of the testis were carried out. The results showed that sperm counts decreased, the spermatozoa were not motile, and several of them possessed abnormalities. The seminiferous epithelium was-thoroughly disrupted and in the seminiferous tubules, fully differentiated spermatozoa were far too limited; cells in the divisional stages were prevalent; multinucleate giant cells were abundant and Leydig cells appeared intact. It is inferred that andrographolide could affect spermatogenesis by preventing cytokinesis of the dividing spermatogenic cell lines. The multinucleate giant cells are comparable to the symplasts generated by cytochalasin-D and ursolic acid due to action at stages V-VII of the spermatogenic cycle. Sertoli cell damage and spermatotoxic effects are also apparent. Thus, the study points to a male reproductive toxic effect of this compound when used as a therapeutic; the study also confirms the possible prospective use of andrographolide in male contraception.

Curative property of Withania somnifera Dunal root in the context of carbendazim-induced histopathological changes in the liver and kidney of rat.

The liver and kidney of rat underwent severe histopathological lesions when treated with a single bolus dose of carbendazim, a fungicide, particularly affecting the hepatocytes and the renal corpuscles, respectively. The effects appear to be manifestations of the microtubule-disrupting activity of carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs. The results indicate that Withania somnifera would be an effective curative for carbendazim-induced histopathological changes in the liver and kidney.

Antifertility effect of Andrographis paniculata (Nees) in male albino rat.

Dry leaf powder of A. paniculata, when fed orally to male albino rats, at a dose level of 20 mg powder per day for 60 days, resulted in cessation of spermatogenesis, degenerative changes in the seminiferous tubules, regression of Leydig cells and regressive and/or degenerative changes in the epididymis, seminal vesicle, ventral prostate and coagulating gland. There was reduction in the weight and fluid content of the accessory glands. The treatment also resulted in accumulation of glycogen and cholesterol in the testis, and increased activities of lactate dehydrogenase in testis and alkaline phosphatase in testis and ventral prostate. The results suggest antispermatogenic and/or antiandrogenic effect of the plant.