Hepato-protective effects of Montelukast against methotrexate-induced hepatotoxicity in rat model

Abstract

Aim: Assessment of the possible Hepato-protective effects of Montelukast against hepatotoxicity induced by MTX in rat model. Materials and methods: A 24 Albino Wister rats were included in this study, they were randomly divided into 4 groups each of 6. Group 1: control group (administered 0.9% N/S 1ml/kg/d ip) for 5 days. Group 2: MTX group (received MTX in a dose of 20mg/kg/day ip) as a single dose at day 1 and observed till day 5 of the experiment. Group 3: Montelukast group (received MTX in a dose of 20mg/kg/d ip as a single dose then Montelukast 10 mg /kg/ d ip for 5days). Group 4: vehicle group received 1ml/kg ip for each rat (10%DMSO + 40%PEG300 + 5% Tween400 + 45% Normalsalin) vehicle solution for 5 days. At day 5 all animals were sacrificed, serum was aspirated for the assessment of ALT, AST, ALP, TSB levels by colorimetric assay. Liver was removed and divided into 2 parts for histopathological examination and for assessment of tissue TNF-alpha, caspase-3, MDA, total antioxidant capacity, and TLR4 levels by ELISA method. Results: Mean serum levels of ALT, AST, ALP and TSB as well as tissue MDA, TNFα, TlLR4, Caspse3 were significantly increased in MTX group compared with the control and vehicle groups together with significant reduction in total antioxidant capacity and obvious histological damage. Whereas meanwhile treatment of rats with Montelukast together with MTX resulted in significant reduction in mean serum levels of ALT, AST, ALP and TSB as well as tissue MDA, TNFα,TlLR4, Caspse3 together with significant increment in total antioxidant capacity and near normal restoration of hepatic tissue architecture. Conclusion: Montelukast has Hepatoprotective effect against MTX induced hepatotoxicity by its antioxidant, anti-inflammatory, and anti-apoptotic properties.