Synthesis of New Methionine Derivatives for the Treatment of Paracetamol - Induced Hepatic Injury

Abstract

The direct pharmacological properties of amino acids and the possibility of using them as carriers for other active pharmacological substances are well known. Methionine, being able to yield the methyl group, is very important in the treatment of hepatic diseases. Paracetamol acute poisoning causes liver injury in both humans and animals. The study is designed to synthesize some new methionine derivatives and to establish a possible correlation between the new structure and the pharmacological properties. To this end, acute experimental poisoning with PanadolВ® (paracetamol) was performed while, for the treatment of liver injury caused by this compound, two original synthesis derivatives of methionine, namely N-(m-nitrobenzoyl)- L-methionine and N-(m-aminobenzoyl)-L-methionine, were used. Male Wistar rats were administered PanadolВ® (paracetamol) per oral (7500 mg/kg). N-(m-nitrobenzoyl)-L-methionine (m-NBM) 50 mg/kg and N-(m-aminobenzoyl)-L-methionine (m-ABM) 50 mg/kg were given intraperitoneally, 30 minutes after PanadolВ® administration. Biochemical parameters such as SGOT, SGPT, serum bilirubin and glycemia were estimated to assess the liver function. PanadolВ® (paracetamol) poisoning produced an increase in serum transaminases, bilirubin and glicemia. These effects were reduced by treatment with m-NBM and especially m-ABM. These biochemical observations were supplemented by histopathological examination of liver sections. The results obtained with m-ABM were comparable with those reported on methionine, which is a recognised antidote in paracetamol poisoning.