Emblica officinalis reverses thioacetamide-induced oxidative stress and early promotional events of primary hepatocarcinogenesis

Abstract

Emblica officinalis is widely used in Indian medicine for the treatment of various diseases. In the present study, it was found that fruits of E. officinalis inhibit thioacetamide-induced oxidative stress and hyper-proliferation in rat liver. The administration of a single necrotic dose of thioacetamide(6.6 mM kg(-1)) resulted in a significant (P < 0.001) increase in serum glutamic oxaloacetic transaminase(SGOT), serum glutamic pyruvic transaminase (SGPT) and gamma-glutamyl transpeptidase (GGT) levels compared with saline-treated control values. Thioacetamide caused hepatic glutathione (GSH) depletion and a concomitant increase in malanodialdehyde (MDA) content. It also resulted in an increase(P < 0.001) in the activity of glutathione-S-transferase (GST), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PD) and a decrease in glutathione peroxidase (GPx) activity (P < 0.001). Hepatic ornithine decarboxylase activity and thymidine incorporation in DNA were increased bythioacetamide administration. Prophylactic treatment with E. officinalis for 7 consecutive days before thioacetamide administration inhibited SGOT, SGPT and GGT release in serum compared with treated control values. It also modulated the hepatic GSH content and MDA formation. The plant extract caused a marked reduction in levels of GSH content and simultaneous inhibition of MDA formation. E. officinalis also caused a reduction in the activity of GST, GR and G6PD. GPx activity was increased after treatment with the plant extract at doses of 100 mg kg(-1) and 200 mg kg(-1). Prophylactic treatment with the plant caused a significant down-regulation of ornithine decarboxylase activity (P < 0.001) and profound inhibition in the rate of DNA synthesis (P < 0.001). In conclusion, the acute effects of thioacetamide in rat liver can be prevented by pre-treatment with E. officinalis extract.