Effect of different doses of S-adenosyl-L-methionine on paracetamol hepatotoxicity in a mouse model

This study investigated the hepatoprotective effects of N-acetylcysteine an d different doses of S-adenosyl-L-methionine after a single intraperitoneal overdose of paracetamol in mice. Plasma concentrations of paracetamol meta bolites were also determined. Female mice (Souris OF1 strain) 16 weeks old and weighing 30 g were fasted for 18 h prior to intraperitoneal (i.p.) admi nistration of 375 mg/kg (2.5 mmol/kg) of paracetamol. Experimental subgroup s included mice administered paracetamol only (control group), those given of N-acetylcysteine 1 g/kg (6.13 mmol/kg) i.p. immediately after paracetamo l overdose (T0) and 6 h after dosing (T6) and those administered S-adenosyl -L-methionine at doses of 20 mg/kg (0.05 mmol/kg) and 1 g/kg (2.5 mmol/kg) i.p. at T0 and T6. Twenty-four hours after paracetamol overdose, mortality and liver necrosis were significantly lower (p < 0.01) in mice treated with 2.5 mmol/kg of S-adenosyl-L-methionine and N-acetylcysteine at T0 as compa red with the remaining subgroups. Plasma ALT concentrations were significan tly lower (p < 0.01) in mice treated with 2.5 mmol/kg of S-adenysl-L-methio nine than in those given N-acetylcysteine. Plasma concentrations of paracet amol metabolites showed an increase in the glucuronide conjugate and a decr ease in the mercapturic acid conjugate in N-acetylcysteine-treated mice and an overall decrease in the conjugation pathway without changes in the oxid ative pathway in S-adenysl-L-methionine-treated animals. We conclude that S -adenysyl-L-methionine at doses of 1 g/kg (2.5 mmol/kg) i.p. was equally ef fective as 1 g/kg (6.13 mmol/kg) N-acetylcysteine for preventing hepatotoxi city after paracetamol overdose in mice. S-adenosyl-L-methionine may be a t herapeutic alternative to N-acetylcysteine as an antidote for poisoning wit h paracetamol. (C) 2000 Prous Science. All right reserved.