Hepatoprotective potential of Phyllanthus niruri and Andrographis paniculata in isoniazid-rifampicin induced hepatotoxicity in rats

Abstract

Background: Isoniazid (INH) and Rifampicin (RIF) are the common drugs causing hepatitis in patients undergoing Antitubercular therapy (ATT). This often results in discontinuation of the therapy or change in the treatment regimen. Free radical injury by drug metabolites has been postulated as cause of liver damage. The herbal extracts of Phyllanthus niruri and Andrographis paniculata possess antioxidant activity.

Methods: Hepatotoxicity was induced in Sprague Dawley rats by administering Isoniazid (100 mg/kg, po) and Rifampicin (100 mg/kg, po) combination for 14 days. Each group of rats were simultaneously treated with P. niruri (125 mg/kg, po), A. paniculata (125 mg/kg, po) and in combination of both for 14 days. Assessment of hepatotoxicity was done by evaluating serum total bilirubin, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), liver superoxide dismutase (SOD), liver catalase levels, and histopathological examination of liver.

Results: There was a significant reduction in the total bilirubin and SGOT levels in the groups treated with P.niruri, A.paniculata and combination of P.niruri and A.paniculata when compared with the INH and RMP treated groups (P<; 0.0001, P = 0.03, P < 0.0001) respectively. The liver SOD and Catalase enzymes were significantly deranged in the group treated with INH and RMP compared to the control animals (P < 0.0001). However, the SOD and Catalase levels were significantly elevated in the groups treated with these protective agents (P < 0.0001) when compared with INH and RMP group. Histopathological examination revealed that in the groups treated with INH and RMP, grades 1 & 2 necrosis was observed than those animals of the normal control group (p = 0.002). However, treatment with P.niruri and A.paniculata extracts showed no signs of necrosis on comparing with the INH and RMP group (p = 0.002).

Conclusion: Extracts of P. niruri and A. paniculata both in monotherapy and combination has hepatoprotective action against the hepatotoxicity induced by Isoniazid and Rifampicin.

Keywords: Andrographis paniculata; Antitubercular therapy; Drug induced hepatitis; Phyllanthus niruri.