International Journal of Medical Science and Clinical Research Studies ISSN(print): 2767-8326, ISSN(online): 2767-8342 Volume 03 Issue 10 October 2023 Page No: 2221-2226 Impact Factor: 6.597 , 19 - i10 - https://doi.org/10.47191/ijmscrs/v3 DOI: 2221 Volume 03 Issue 10 October 2023 Corresponding Author: Samuel Dada Diclofenac-Induced Alterations in Renal Antioxidants and Cytokines in Male Wistar Rats Samuel Dada 1,2 , Olabode Akintoye 3 , Okechukwu Ezekpo 1 , Oluwasina Dada 4 , Joseph Sanya 1 1 Department of Human Physiology, College of Medicine and Health Sciences, Afe Babalola University Ado Ekiti State, Nigeria. 2 Nephrology Unit, Department of Medicine, Ekiti State University Teaching Hospital/ Ekiti State University, Ado Ekiti, Nigeria. 3 Department of Physiology, Ekiti State University, Ado Ekiti, Nigeria. 4 Renal Surgery Department Queen Elizabeth Hospital Birmingham, UK. ABSTRACT ARTICLE DETAILS Introduction: Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that is widely used to treat pain and inflammation. However, diclofenac use has been associated with a number of side effects, including renal toxicity. The mechanisms underlying diclofenac-induced nephrotoxicity are not fully understood, but oxidative stress and inflammation are thought to play a role. This study investigated the effects of diclofenac on renal antioxidants and cytokines in male Wistar rats. Method: Male Wistar rats were randomly divided into three groups: control group, low and high-dose diclofenac group (10 and 30 mg/kg/day) respectively. Treatment was administered for 10 days. At the end of the study, the rats were sacrificed, serum samples and kidney homogenates were analysed for markers of oxidative stress, lipid peroxidation and inflammation including assessment of renal function. Result: Diclofenac treatment caused a significant decrease in renal antioxidants, including superoxide dismutase (SOD) and glutathione peroxidase (GPx) compared to the control, (0.78±0.11 versus 0.61±0.14), (214.80±46.37versus 149.70±39.43) P <0.05 respectively. In addition, a significant increase in the level of MDA and renal cytokine (TNF-α) was observed between the control and treated group of rats (2.62±0.29 versus 8.74±4.34, p<0.001) and (1276.0±90.18 versus 222.90±38, P=<0.00) and respectively. The high-dose diclofenac caused a significant increase between the treated and control group of rats respectively and deranged renal function test (serum creatinine and renal KIM-1) Conclusion: This study provides evidence that diclofenac may induce alterations in renal antioxidants, and mediates oxidative stress and inflammation with consequent kidney injury in male Wistar rats. KEYWORDS: Diclofenac, antioxidant, inflammation, nephrotoxicity, cytokines Published On: 10 October 2023 Available on: https://ijmscr.org/ INTRODUCTION Diclofenac is an analgesic and belongs to the non-steroidal anti-inflammatory drug (NSAID) that is widely used to treat pain and inflammation. It works by inhibiting the production of prostaglandins, which are responsible for inflammation. [1, 2] However, diclofenac use has been associated with a number of side effects, including renal toxicity. Nephrotoxicity is a major concern, as it can lead to kidney failure. [1, 3, 4] The exact mechanism of diclofenac-induced renal toxicity is not fully understood. However, it is thought to be mediated by inflammation, oxidative stress, and depletion of renal antioxidant molecules such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).[3, 5-7] Oxidative stress is a condition in which there is an imbalance between the production of free radicals and the body's ability to neutralize them. Free radicals are unstable molecules that can damage cells and tissues. Renal damage associated with diclofenac has also been linked with inflammation, a complex biological process that is characterized by the release of inflammatory cytokines that play a significant role in the immune response. Tumour necrotic factor alpha and Interleukin-1β (TNF-α and IL-1β) are involved in the recruitment of inflammatory cells to the site of infection or injury. They also promote the release of other pro-