The hepatoprotective effect of Phyllanthus amarus Schum. & Thonn. was studied on paracetamol hepatotoxicity in rats by monitoring serum transaminase (SGOT and SGPT), alkaline phosphatase (ALP) and bilirubin as well as by histopathological examination of liver. Furthermore, the hepatoprotective mechanisms were investigated by determining the amount of paracetamol and its metabolites (glucuronide, sulfate, cysteine and mercapturic acid conjugates) in urine and pentobarbital-induced sleeping time to indicate the inhibition on cytochrome P450. The involvement of glutathione was evaluated by determining hepatic reduced glutathione. Its antioxidant activity was estimated by DPPH (1,1-diphenyl-2picrylhydrazyl) assay. Hot water extracts of P. amarus (0.8, 1.6 or 3.2 g/kg) were orally administered b.i.d. for 7 d prior, 2 d after, or 7 d prior and 2 d after single oral dose of paracetamol (3 g/kg). The results showed that the extract at 1.6 and 3.2 g/kg decreased the paracetamol-induced hepatotoxicity as indicated by the decrease in SGOT and SGPT, bilirubin and histopathological score while the ALP did not change. It is evident that the hepatoprotective mechanism of this plant was neither related to inhibition on cytochrome P450, nor induction on sulfate and glucuronide conjugation pathways of paracetamol, but partly due to the antioxidant activity and the protective effect on the decrease of hepatic reduced glutathione. These results support the value of P. amarus, which has been used in folk medicine for the treatment of toxic liver diseases.

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