Nephroprotective effects of melatonin and Nigella sativa against renal ischemia-reperfusion injury

Abstract

Introduction: Renal ischemia-reperfusion (IR) injury is a major cause of acute kidney injury and is strongly associated with oxidative stress, inflammation, and apoptosis. Melatonin and Nigella sativa possess well-documented antioxidant and anti-inflammatory properties that may provide renoprotective effects against IR-induced renal damage. Objective: The present study aimed to evaluate the potential nephroprotective effects of melatonin and Nigella sativa, individually and in combination, against renal IR injury in rats. Methods: Experimental renal IR injury was induced in rats by bilateral renal pedicle clamping followed by reperfusion. Animals were divided into experimental groups: Sham, IR, melatonin-treated, Nigella sativa-treated, and combined treatment. Biomarkers of renal function, oxidative stress, inflammatory cytokines, apoptotic markers, and kidney injury molecule-1 (KIM-1) were analyzed. Histopathological changes of the renal tissue were examined using hematoxylin & eosin staining. Results: In the renal IR injury group, serum urea, creatinine, tumor necrosis factor-alpha, interleukin-6, and KIM-1 levels, as well as renal malondialdehyde and B-cell lymphoma 2-associated X protein levels, were significantly higher, whereas renal tissue reduced glutathione and B-cell lymphoma 2 levels were significantly lower, compared with those of the Sham group. Melatonin and Nigella sativa treatment significantly reduced these biochemical and histopathological changes. Importantly, the combination therapy was associated with stronger renoprotective effects than either therapy alone, as reflected by improved renal function, lower levels of oxidative stress and inflammatory responses, restoration of apoptotic balance, and better preservation of renal histological architecture. Conclusion: The results of the present study suggest that melatonin and Nigella sativa exert potent nephroprotective effects against IR injury via their modulation of oxidative stress, inflammation, apoptosis, and KIM-1 protein levels. Co-treatment with combined administration resulted in more powerful protective effects and could be a potential therapeutic option for the prevention of IR-associated renal damage.