EVALUATION OF OXIDATIVE STRESS INDUCED HEPATOTOXICITY PRODUCED BY CISPLATIN IN MALE SPRAGUE DAWLEY RATS

Abstract

Objective: To study the effect of cisplatin administration on oxidative stress induced hepatotoxicity in male Sprague Dawley rats.

Study Design: Randomized controlled trial.

Place and Duration of Study: Study was conducted at department of Physiology, Army Medical College, Rawalpindi. Duration of study was 18 months from Oct 2014 to Apr 2016.

Material and Methods: The trial was performed on sixty male Sprague Dawley rats which were distributed randomly into two groups of 30 rats each. Group I received placebo whereas group II received intraperitoneal cisplatin 2mg/kg body weight two times a week for the period of 4 weeks. After successful treatment, animals were sacrificed and terminal blood sample was collected and used for estimation of serum AST, ALT, albumin
and 8-isoprostane. Dissection of rats were done and liver tissue sampled. Tissue homogenate was prepared from liver sample which was used for estimation of total glutathione levels.

Results: In group I, 8-isoprostane was 18.31 ± 3.35 pg/ml, total glutathione was 4.29 ± 0.42 μmol/L, ALT was 36.93 ± 4.72 IU/L, AST was 124.2 ± 12.75 IU/L and Albumin was 4.11 ± 0.26 g/dl whereas in group II, 8-isoprostane was 67.9 ± 8.14 pg/ml, total glutathione was 1.92 ± 0.28 μmol/L, ALT was 87.17 ± 6.47 IU/L, AST was 357.7 ± 19.37 IU/L and Albumin was 2.12 ± 0.25 g/dl. Levels of serum 8-isoprostane, ALT and AST were significantly raised (p<0.001) whereas serum albumin and total glutathione in liver tissue were found significantly low (p<0.001) in group II as compared to group I.

Conclusion: Cisplatin treatment causes hepatotoxicity by increased production of reactive oxygen species in male Sprague Dawley rats.