Protective Effect of Grape Seeds Proanthocyanidins against Naphthalene-induced Hepatotoxicity in Rats

Oxidative stress with subsequent production of reactive oxygen species has been postulated as one of the mechanisms of naphthalene toxicity. In the present study, the effect of oral administration of the natural antioxidant and free radical scavenger, proanthocyanidins present in grape seeds (GSP, 10 or 50 mg kg, p.o.), has been investigated in rats following the concomitant administration of naphthalene (1 g kg, p.o., 15 days) and measurement of selective parameters indicative of liver function and oxidative stress. Serum aminotransferases (ALT and AST), alkaline phosphatase (AP) activities, and total bilirubin (T Bil) oncentration were measured, as well as hepatic tissue lipid peroxidation (MDA), DNA fragmentation, and glutathione (GSH) contents. The effects of GSP on naphthalene-evoked changes in the above-mentioned parameters were compared with the known hepatoprotectant agent, silymarin. Naphthalene hepatotoxicity was evident by the significant elevation of rat serum activities of ALT, AST, AP, and T Bil concentration. This effect was accompanied with significant increases in MDA and DNA fragmentation plus the depletion of GSH in hepatic tissues. Concurrent administration of GSP significantly attenuated the naphthalene-induced disturbances in serum liver function enzymes, and markedly antagonized the lipid peroxidation, DNA fragmentation and GSH depletion induced by naphthalene in hepatic tissues. In conclusion, GSP appears to be a potent candidate to ameliorate the oxidative stress and hepatotoxicity associated with naphthalene in rats.