Diclofenac induced-acute kidney injury is linked with oxidative stress and pro-inflammatory changes in Sprague Dawley rats

Abstract

Objectives: Diclofenac induces oxidative stress in the body and became the main cause of nephrotoxicity and acute kidney injury (AKI). The traditional markers of AKI are blood urea and serum creatinine which are regarded as low sensitive and low specific in detection the early renal damage. Therefore, the aim of present study was to evaluate oxidative stress and pro-inflammatory biomarkers in diclofenac induced- AKI in rats. Methods: Twenty Sprague Dawley Male rat were used and randomly divided in to 2 groups. Group1 (n=10): Rats treated with distilled water plus normal saline for 12 days. Group2 (n=10) : Rats treated with distilled water plus diclofenac 15mg/kg for 12 days. Rat body weight, body mass index and estimated glomerular filtration rate (eGFR) were evaluated in both groups. Blood urea, serum creatinine, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GSH), Neutrophil Gelatinase Associated Lipocalin (NGAL) , kidney injury molecules (KIM-1) and Cystatin-c were estimated. Results: Diclofenac 15mg/kg led to significant AKI through elevation of blood urea and serum creatinine with significant reduction of eGFR. KIM-1 serum level was significantly elevated with high sensitivity and specificity compared to the other tested biomarkers. Conclusion: KIM-1 serum level is more sensitive and specific with high accuracy compared to the other renal biomarkers in diclofenac induced- AKI. Estimation of KIM-1 serum levels should be regarded as a cornerstone for early detection of AKI in high risk patients.

Resveratrol mitigates diclofenac‐induced hepatorenal toxicity in rats via modulation of miR‐144/Nrf2/GSH axis

“…The oxidative stress induced by diclofenac is related to the production of reactive metabolites, 5‐hydroxy diclofenac, and N,5‐dihydroxy diclofenac, which increase the levels of free radicals and result in damage to different tissues. [ 34,38 ] As many cellular and molecular events compromising oxidative stress are fine‐tuned by miRNAs, [ 39 ] our data suggest that miR‐144 is implicated in diclofenac‐induced hepatorenal damage and confirms the notion that oxidative stress is an important player in diclofenac‐triggered hepatorenal injury. On the contrary, miR‐144 was downregulated during protection or treatment with resveratrol.…”

The Flavonoid Hesperidin Methyl Chalcone Targets Cytokines and Oxidative Stress to Reduce Diclofenac-Induced Acute Renal Injury: Contribution of the Nrf2 Redox-Sensitive Pathway

“…This particular aspect highlights the fact that diclofenac may induce AKI via a different primary pathological mechanism. It is postulated that a mechanism related to the induction of oxidative stress and/or reduction of antioxidant capacity may be determinant for diclofenac-induced nephrotoxicity [ 14 , 15 ]. In this sense, investigations have shown that through oxidative stress, increased cytokine release, and nuclear factor κB (NFκB) activation, diclofenac may induce AKI [ 1 , 9 , 16 ].…”

Histological changes induced by Piroxicam on the hepatic and renal tissues of mice with and without administration of Peppermint oil

“…The tubular cell damage detected in this study was accompanied by inflammatory cells infiltration that invaded into the intertubular tissues to minimize the injury. Similar acute kidney injury has been known to be induced by Diclofenac [30]. Other studies suggest that toxicity of Piroxicam comes about because it acts as a potent chelator of zinc, copper, selenium and manganese -which are the cofactors of the endogenous antioxidant, and because it has a notable negative impact on their scavenging activity [31].…”