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

Abstract

Despite the extensive therapeutic uses of diclofenac, it may cause several adverse effects, including hepatorenal injury. The antioxidant and anti-inflammatory properties of resveratrol, a polyphenolic compound, make the agent effective in ameliorating a variety of drug-induced injuries. This study investigated the potential beneficial effects of resveratrol on diclofenac-induced hepatorenal toxicity and explored the role of miR-144 and its relationship to oxidative stress and inflammation triggered by diclofenac. Rats were divided into four groups: control; diclofenac group received diclofenac (10 mg/kg/day, intraperitoneal [ip]) for 7 days; prevention group received resveratrol concomitantly with diclofenac for 7 days; and the treatment group received diclofenac for 7 days followed by resveratrol (20 mg/kg/day, per oral) for another 7 days. Diclofenac administration induced a significant increase in serum hepatorenal biomarkers and histopathological aberrations. In addition, diclofenac upregulated miR-144 while reducing nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and glutathione (GSH) content.Moreover, diclofenac induced tissue inflammation and apoptosis as evidenced by increased protein expression of nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), and caspase-3. Intriguingly, resveratrol prevention or treatment significantly mitigated the toxic effects of diclofenac as manifested by normalization of the hepatorenal functions and amelioration of the histopathological changes.Resveratrol also triggered miR-144 downregulation with Nrf2 upregulation.Consequently, resveratrol showed hepatorenal antioxidant, anti-inflammatory, and antiapoptotic activities as manifested by improvement in the antioxidant markers along with a decline in NF-κB, TNF-α, and caspase-3 expressions. In conclusion, this study demonstrates a potential therapeutic role of resveratrol in mitigating diclofenac-induced hepatorenal insult, possibly via modulating miR-144/Nrf2/ GSH axis.

Biochemical and histopathological evaluation of the potential ameliorating effects of Spirulina platensis against acute hepatorenal toxicity of diclofenac sodium in male rats

“…Also, the histopathological findings of the current study proved the hepatic damage induced by diclofenac, which is consistent with the previous report of (Esmaeilzadeh et al, 2020). Concerning renal function, previous studies by (Izak-Shirian et al, 2022) and (Elbaz et al, 2022) reported obvious nephrotoxicity after diclofenac administration to rats at a dose (50 mg/kg) for 5 days and (10 mg/kg) for 7 days. These results were consistent with the current study.…”

Research progress of SIRTs activator resveratrol and its derivatives in autoimmune diseases

“…found that resveratrol also triggers the downregulation of miR-144 by upregulating the expression level of Nrf2.Consequently, resveratrol showed hepatorenal antioxidant, anti-inflammatory, and antiapoptotic activities as manifested by improvement in the antioxidant markers along with a decline in NF-κB, TNF-α, and caspase-3 expressions. In summary, this study demonstrated that resveratrol has potential therapeutic effects in alleviating liver and kidney damage induced by nonsteroidal anti-inflammatory drugs ( 275 ).…”

Ameliorating diabetes‐induced testicular dysfunction by modulating PKC/Nrf2/Bcl‐2 signaling: Protective role of sulbutiamine

“…Nrf2 is a nuclear transcription factor which has an essential role in the antioxidant defense process regulation. 49,50 Normally, Nrf2 is degraded in the cytoplasm. 49 Under stressed conditions, it undergoes nuclear translocation, where it binds to the antioxidant response element (ARE) to induce the transcription of many antioxidant enzymes such as glutathione S-transferase, heme oxygenase-1, catalase, and superoxide dismutase.…”