EFFECTIVE ALLEVIATION OF METHOTREXATE INDUCED HEPATOTOXICITY BY MURRAYA KOENIGII LEAF EXTRACTS

Highland H. N.*, Kanwar R., Engineer A. and Desai K. R.

ABSTRACT

Drug induced hepatotoxicity is a distressing cause of liver insult, since the liver is the prime site of metabolism and biotransformation. Hence the present investigation was aimed at evaluating the ameliorative action of potent herbal extracts of Murraya koenigii to counteract the drug induced liver injury. These extracts, aqueous and hydro-alcoholic are a rich source of bioactive phytochemicals known for its anti-inflammatory, antioxidant and immunomodulatory activity. Male albino mice weighing 35-40 gm were treated with Murraya koenigii (250mg/kg body weight) extracts against Methotrexate induced toxic model for 15 days. The body weight was insignificantly elevated following methotrexate dosing, however this change was reversed by administration of the Murraya koenigii extract. The decline in liver weight was evidence of the inhibitory effect of Methotrexate on liver biosynthetic activity. Although the extracts were found to restore the fall in liver weight, complete recovery in this gravimetric parameter was not observed. Biochemical analysis for key liver markers revealed a significant elevation in activity of liver transaminases, indicative of hepatic inflammation. Oral administration of both extracts could effectively curb the rise in ALT and AST, where the hydroalcoholic extract appeared to be more potent. In addition, the significant decline observed in the activity of enzymes involved in oxidative and energy metabolisms, was also efficiently ameliorated by M. koenigii extract treatment. Further metabolic insult due to Methotrexate dosing resulted in a significant fall in protein and cholesterol levels, reflecting inhibition of metabolic turnover. Both extracts were able to bring about a significant recovery in these metabolite levels, possibly expediting liver repair. Thus, the extracts being a rich source of antioxidants could lead to recovery, mitigating the induced toxic injury of Methotrexate, possibly by effectively scavenging the free radicals generated. It is also known that Murraya koenigii phytochemicals manifest anti- inflammatory effects by suppression of inflammatory inducers. Thus owing to the rampant, unsupervised use of medications, simultaneous administration of Murraya koenigii leaf extracts could provide the much required hepatoprotection to alleviate liver damage.

Keywords: Methotrexate, Liver, Mice, Murraya koenigii.