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

Azathioprine (AZA) is an immunosuppressant medication that has toxicity to kidneys and liver. This study aimed to investigate the protective activity of carvacrol (CAR) against hepatorenal toxic activity of AZA in male Wistar rats.

All study rats were divided into five groups: control (saline, ip); azathioprine-only (AZA 50 mg/kg, ip), Sily+AZA (Silymarin 50 mg/kg, gavage), CAR+AZA (CAR 10 mg/kg, gavage), and CAR+AZA (CAR 20 mg/kg, gavage) groups. Silymarin was used as the standard hepatoprotective drug. The drugs were administered once daily for 21 days in III-V groups, and a single dose of AZA was injected on the seventh day of the experiment.

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 < 0.05). Co-treatment of CAR (both doses of 10 and 20 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 < 0.05). This protective effect was greater in CAR 10 compared to 20 mg/kg doses, which was comparable to silymarin.

This study demonstrated that the renal and nephrotoxic activities of AZA could be attributed to the generated increased oxidative stress, as well as to the CAR with antioxidant effect similar to that in silymarin, which protected these tissues against AZA-induced nephrotoxicity hepatotoxicity.