Experimental Evaluation of Prophylactic and Therapeutic Antioxidant Potential of Trimetazidine in Carbon Tetrachloride Induced Oxidative Stress in Rats

Abstract

Introduction: Exposure to various drugs and chemicals lead to oxidative stress. Carbon Tetrachloride (CCl4) produces rise in oxidative stress leading to hepatic damage. The drug Trimetazidine (TMZ) shows hepatoprotective activity but its mechanism is not known. The present study would help in establishing antioxidant activity of TMZ as probable mechanism. Aim: To evaluate the antioxidant potential of TMZ in CCl4 induced oxidative stress when given prophylactically/therapeutically in rats. Materials and Methods: An experimental animal study was conducted on 80 adult Wistar rats of either sex (weight-150 to 200 gm) from March 2010 to December 2010 in Bharati Vidyapeeth Medical College, Pune, Maharashtra, India. Randomly, all animals were grouped into 10 equal groups. Group i was normal control (received only water). To induce oxidative stress CCl4 (0.5 mL/kg/d i.p.) was given to all the animals of Group ii to Group x for seven days. The TMZ was given in two doses, TMZ1 (5 mg/kg orally for Group iii and vii) and TMZ2 (10 mg/kg orally for Group iv and viii). Positive standard control (Group v and Group ix) received Liv.52 (1 mL/kg orally). Group vi and Group x received combination of TMZ1 (5 mg/kg orally)+Liv.52 (1 mL/kg orally). Drug treatment was given to animals in group iii, iv, v and vi for 1-14 days (preventive group) and in group vii, viii, ix and x from day 8 to day 14 (therapeutic group). On 15th day, rats were sacrificed and dissected for collection of liver. Part of the livers was homogenised to assess oxidative stress marker enzymes Malondialdehyde (MDA), Superoxide Dismutase (SOD) spectrophotometrically. Statistical analysis was done with one- way Analysis of Variance (ANOVA) followed by post-hoc analysis (Dunnett’s test) using GraphPad Prism 5.0 software. Results: Trimetazidine (5 mg/kg and 10 mg/kg) significantly reduced MDA levels and increased SOD levels when compared with CCl4 treated group suggested antioxidant activity. Combined administration of Liv.52 and TMZ1 also reduced oxidative stress and increased antioxidant activity. Conclusion: Results of the present study suggested that increased oxidative stress was significantly attenuated by drug TMZ in dose dependant manner when compared with the CCl4 group. The antioxidant potential of prophylactic and therapeutic administration of TMZ was comparable. The increased antioxidant effect by Liv.52+TMZ1 combination was only due to the additive antioxidant effects of Liv.52 and TMZ or any other mechanism was involved, needs to be further evaluated.