The nephroprotective effect of ellagic acid against diclofenac-induced renal injury in male rats: role of Nrf2/HO-1 and NF-κB/TNF-α pathways

Despite the promising effect of the nonsteroidal anti-inflammatory drug (NSAIDs) on controlling the chronic symptoms of different diseases, their toxicity has restricted the long-term administration of these agents. The lack of suitable substitution provides opportunities for innovation of combined-modality strategies that could reduce the toxic side effects of these drugs. In the present study, we aimed to evaluate the protective effect of ellagic acid, a phenolic compound found in plants, on diclofenac-induced nephrotoxicity. The results of the treatment of 32 Wistar rats with diclofenac (0 mg/Kg) and/or ellagic acid (10 mg/Kg) for seven days showed that, unlike diclofenac that shifted the ratio of the redox system in favor of oxidative stress, ellagic acid reduced the tissue levels of malondialdehyde (MDA), protein carbonyl (PC) and diminished serum nitrite content. Moreover, through upregulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), ellagic acid might increase the activity and the tissue levels of several antioxidant enzymes such as catalase (CAT), superoxidase dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH) in diclofenac-treated rats. This phenolic agent also prevented diclofenac-mediated inflammatory responses by suppressing the expression of nuclear factor (NK)-kappa B/tumor necrosis factor (TNF)-alpha and reducing the number of infiltrated lymphocytes in the kidney tissue. Taken together, our study demonstrated that ellagic acid may produce a protective effect against diclofenac-induced renal failure by exerting both antioxidant and anti-inflammatory properties. This finding indicates that this agent might be a valuable candidate to be used alongside NSAIDs such as diclofenac to alleviate their side effects.

Automated summary

Ellagic acid demonstrates a protective effect against diclofenac-induced nephrotoxicity by reducing oxidative stress, increasing the activity of antioxidant enzymes, and suppressing inflammatory responses. This finding suggests that ellagic acid may be a valuable candidate to alleviate the side effects of NSAIDs such as diclofenac.