Protective Role of the Combination of Resveratrol and N-Acetylcysteine in Preventing Acute Paracetamol-Induced Nephropathy in Rats

(Ali A. Shati)

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Abstract

As an overdose of Paracetamol (PCM) is nephrotoxic, the present study aimed to investigate and compare the individual therapeutic effects of Resveratrol (RES), N-acetyl cysteine (NAC), and their combination against PCM induced nephrotoxicity in rats in addition to illustrate possible mechanisms of action. Fifty adult Wistar rats were divided into 5 groups (n=10/group): 1) control group, 2) PCM group (1000 mg/kg b.wt), 3) PCM post-treated with RES (25 mg/kg b.wt), 4) PCM post-treated with NAC (1.2 g/kg b.wt), and 5) PCM post-treated with concomitant RES and NAC. PCM was administered during the first 2 days and all other treatments were administered intraperitoneally daily for the post PCM induction five days. At the end of the study, serum electrolytes, renal levels of oxidative stress marker, mRNA expression levels of ?-glutamyl cysteine ligase (?-GCL), and Na+/K+ ATPase were measured. PCM intoxication caused oxidative stress-induced renal damage as evident by the inhibition of mRNA expression of ?-GCL and glutathione (GSH) levels, and by the inhibition of the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST). PCM induced renal damage was mediated by a parallel decrease in activity and expression levels of Na+/K+ ATPase. However, while delayed NAC administration to post PCM intoxicated rat poorly improved these parameters and changes in kidney structure, the effect of RES was also partially but more profound. On the other hand, concomitant administration of both NAC and RES completely reversed the alterations of serum electrolytes, renal architectures histological parameters, serum electrolytes, oxidative stress parameters, renal architectures histological parameters, and resulted in normal renal mRNA expression of both ?-GCL and Na+/K+ ATPase. These data suggests that NAC and RES act in a synergistic manner and completely ameliorate PCM induced nephrotoxicity. Keywords: N-acetylcysteine; Nephrotoxicity; Oxidative stress; Paracetamol; Resveratrol.
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