Inflammatory stress and idiosyncratic drugs hepatotoxicity in rabbit

Abstract

Idiosyncratic drug hepatotoxicity is none or time-related, unpredictable, occur infrequently and can be fatal. It was proposed that inflammatory or oxidative stress occurs randomly in patients even after asymptomatic incidence can precipitate drug hepatotoxicity. To measure the hepatotoxicity of diclofenac in rabbit serum following the incidence of inflammatory stress by lipopolysaccharide (LPS) and correlate this to various stress parameters as Malondialdehyde (MDA). 24 rabbits were divided into four groups (6 each) according to the type of treatment. Group 1: control (received normal saline). Group 2 received diclofenac sod. (5mg/kg, orally 3times daily for three days). Group 3: received lipopolysaccharide (150μg/kg, i.v, 24 hours before killing. Group 4: received diclofenac sod. + Lipopolysaccharide (5mg/kg orally + 150μg/kg, i.v 24 hours before killing). Then for each animal were measure, liver M D A, liver enzymes. LPS potentiated the hepatotoxic effect of diclofenac sod. The effect is mediated by oxidative and inflammatory reactions as demonstrated by increase in a liver tissue M D A.