Toxic Effects of Methotrexate on Rat Kidney Recovered by Crocin as a Consequence of Antioxidant Activity and Lipid Peroxidation Prevention

Background: The application of methotrexate (MTX) as a chemotherapy agent and immune system suppressant has various side effects. Crocin, a xanthine derivative plant, has many therapeutic benefits. This study was planned to assess the effect of crocin on renal toxicity of MTX in a rat model. Methods: Forty eight rats were divided randomly into eight groups (n = 6), which received normal saline, MTX, crocin, and MTX + crocin for 28 days intraperitoneally. The levels of oxidative stress in kidney and blood serum were measured, and the kidney was analyzed histologically. Results: MTX caused an enhancement in the levels of thiobarbituric acid reactive substances and biochemical marker (creatinine and blood urea nitrogen [BUN]). Besides, a significant decrease was observed in tissue parameters and antioxidant capacity compared to the normal control group (p < 0.001). The crocin and crocin + MTX decreased the biochemical markers, the levels of thiobarbituric acid reactive species, and tissue parameters considerably at entire dose (12.5, 25, and 50 mg/kg) and enhanced the antioxidant capacity levels compared to the MTX group (p < 0.001). Conclusion: Administration of crocin improves the damage caused by MTX in rats. The crocin by the establishment of balance in the levels of antioxidant prevents the damage to the renal cell membrane, and subsequently the renal damage repairs.