Protective effect of carvacrol against hepato-renal toxicity induced by azathioprine in rats

Background and aims: Azathioprine (AZA) is an immunosuppressant medication that has toxicity to kidneys and liver. This study aimed toinvestigate the protective activity of carvacrol (CAR) against hepatorenal toxic activity of AZA in male Wistar rats.Methods: All study rats were divided into five groups: control (saline, ip); azathioprine-only (AZA ۵۰ mg/kg, ip), Sily+AZA (Silymarin ۵۰mg/kg, gavage), CAR+AZA (CAR ۱۰ mg/kg, gavage), and CAR+AZA (CAR ۲۰ mg/kg, gavage) groups. Silymarin was used as the standardhepatoprotective drug. The drugs were administered once daily for ۲۱ days in III-V groups, and a single dose of AZA was injected on theseventh day of the experiment.Results: AZA-intoxicated rats exhibited an elevation in aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase(ALP) activity in serum, as well as an increase in extent of lipid peroxidation. Activities of enzymatic antioxidants (superoxide dismutase –SOD, catalase - CAT) in the serum, liver, and kidney were decreased as for the AZA group (P < ۰.۰۵). Co-treatment of CAR (both doses of۱۰ and ۲۰ mg/kg) lowered the serum transaminases and ALP level, the elevation of endogenous enzymes levels, and the malondialdehyde(MDA) in serum and both tissues (P < ۰.۰۵). This protective effect was greater in CAR ۱۰ compared to ۲۰ mg/kg doses, which was comparableto silymarin.Conclusion: This study demonstrated that the renal and nephrotoxic activities of AZA could be attributed to the generated increasedoxidative stress, as well as to the CAR with antioxidant effect similar to that in silymarin, which protected these tissues against AZA-inducednephrotoxicity hepatotoxicity.

Keywords:

Azathioprine , Carvacrol , Silymarin , Nephrotoxicity , Hepatotoxicity