Oral administration of Azadirachta indica (L.) seed kernel active principle protects rat liver hepatocytes and testis seminiferous tubules from phenobarbitol-induced damage.

The male albino rat testis and liver showed tissue modification upon exposure to phenobarbitol (PB), 24 mg/100 g of body weight, for about 3 weeks and upon staining of their sections with hematoxylin and eosin. In this procedure, the control liver showed normal hepatocytes with centrally placed nuclei, and the PB-treated hepatocyte showed degeneration of cytoplasm and nucleus, necrosis and fragmentation of nucleus, and pushing of nucleus to periphery. The control rat testis showed epithelial layer having broad seminiferous tubules, spermatids, mature spermatozoa, and lumen of seminiferous tubules, and the PB-treated rat testis showed degenerative and necrotic changes in seminiferous tubules and clumping of seminiferous tubules. These changes almost returned to normal conditions in rat liver and testis upon the oral administration of an antioxidant that is present in Azadirachta seed-kernel extract (ASKE, 100 mg/kg body weight). In the case of enzymes, glutathione transferase and glutathione peroxidase were induced upon PB or ASKE treatment and the combination of both the treatments. The lipid peroxides were reduced in all the three cases in both liver and testis. The histological studies and enzymatic analysis revealed that the potential role of ASKE in the protection of the testis and liver tissues from PB-induced damage.

A comparative study on the effect of phenobarbitol and beta-methylcholanthrene on glutathione S-transferases of rat testis.

Glutathione S-transferases (GSTs; EC, 2.5.1.18) ubiquitously distributed in all life forms, are a family of multigene and multifunctional dimeric proteins, which play a main role in drug detoxication. On purification and on electrophoresis, rat testicular glutathione S-transferases showed that it comprises of four subunits, Yc of alpha class, Yb and Ybeta of mu class and Ydelta of pi class. On chromatofocusing they were resolved into six anionic and four cationic isozymes. The substrate specificity studies and immunoblot analysis of testis proteins revealed that Ydelta of pi class GST was induced predominantly in response to phenobarbitol and Yc of alpha class and Ybeta of mu class were elevated specifically on treatment with methylcholanthrene (MC). These results show that structural variation between the two carcinogens induces different types of GST subunits. Therefore, these subunits may be used as marker proteins for specific chemical toxicity of rat testis.