Protective Effect of Melatonin and Mycophenolate Mofetil Against Nephrotoxicity Induced by Tacrolimus in Wistar Rats

Abstract

Although Tacrolimus (TAC) is a potent and well-tolerated drug, it has some side effects. Melatonin and mycophenolate mofetil (MMF) have some protective properties against drug-induced damage. We aimed to evaluate TAC-induced nephrotoxicity and the protective effect of melatonin and MMF against this injury in rats. The animals were divided into five equal groups (n=6): Control group (untreated), group II TAC, group III as the TAC + melatonin, group IV as the TAC + MMF, and group V as the TAC + melatonin + MMF. TAC was applied orally, 2 mg/ kg once daily. Melatonin and MMF were applied orally 10 mg/kg once and 40 mg/kg once daily, respectively. In the TAC group, kidney tissue malondialdehyde (MDA), total oxidative status (TOS), interleukin-1, and tumor necrosis factor-alpha levels were higher, and catalase and total antioxidant status (TAS) levels were lower. Severe histopathologic changes such as glomerular congestion, intertubular hemorrhage, hyaline formation, degenerative-necrotic tubules epithelium, and mononuclear cell infiltration were seen in the TAC group. There was a clear improvement in the groups in which melatonin and MMF were used together with TAC. It was shown that TAC causes nephrotoxicity through oxidative stress. Melatonin and MMF together or separately protect the kidney against oxidative stress damage caused by TAC.