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Paracetamol (also called acetaminophen, or APAP) overdose causes acute damage to the liver and kidneys in both humans and experimental animal models via the induction of the oxidative stress pathway. We sought to determine whether the com bined antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against kidney injury induced b y a toxic dose of APAP in a rat model of APAP-induced acute kidney injury. Rats were either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Harvested kidney tissues were prepared for light microscopy staining, and tissue samples were assayed for (i) biomarkers of oxidative stress and antioxidant, malondialdehyde (MDA) and sup eroxide dismutase (SOD); and (ii) biomarkers of inflammation, tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6). Hematoxylin and eosin (H&E) stained images showed that APAP overdose induced acute kidney injury as demonstrated by widening of glomeruli space (Bowman space), tubular dilatation, numerous cellular debris in the renal tubules with tubular epithelial degeneration, and vac uolization, which were effectively protected by RES+QUR except a partial protection of the glomeruli space was observed. In addition, APAP significantly (p<0.05) modulated tissue levels of MDA, SOD, TNFα, and IL-6, which were protected by RES+QUR. Furthermore, a significant (p<0.0001) positive correlation was observed between glomeruli space and TNFα, (r=0.8899), IL-6 (r=0.8986), and MDA (r=0.8552), whereas glomeruli space scoring versus SOD showed negative correlation (r= 0.7870). We conclude that resveratrol plu quercetin substantially protects against APAP-induced acute kidney injury in rats, possibly via the augmentation of antioxidant s and inhibition of oxidative stress and inflammation.

Inhibition of Paracetamol-Induced Acute Kidney Damage in Rats Using a Combination of Resveratrol and Quercetin