ABSTRACT
Nephrotoxicity is a frequent and severe side effect of 5-fluorouracil (5-FU) chemotherapy which limits its use clinically regardless of being one of the most promising chemotherapeutic agents. Here, we assessed the nephroprotective activity of two structurally related phenolic acids 2-pyrocatechuic acid (2,3 dihyroxybenzoic acid) and gentisic acid (2,5 dihyroxybenzoic acid) against 5-FU induced nephrotoxicity in Wistar rats. Intraperitoneal administration of 5-FU at a dose of 20 mg/kg once a day for 5 days produced a significant elevation in serum parameters of the kidney such as uric acid, urea, creatinine, sodium and potassium levels along with severe histopathological changes in renal tissues of rats indicating severe nephrotoxicity. Administration of 2-pyrocatechuic acid (2-PCA) at 10, 30 and 100 by oral route for 9 days and additional 5 days with 5-FU resulted in an amelioration of altered serum parameters in a dose-dependent manner. Moreover, 2-PCA attenuated the renal damage produced by 5-FU demonstrating its efficacy as a nephroprotective agent for the prevention as well as amelioration of 5-FU induced nephrotoxicity. None of the doses of gentisic acid (GA) were found to be effective in this posology when given orally.
ABSTRACT
The cerebral ischemia in rats was induced by occluding bilateral common carotid arteries (BCCAO) for 30 min., followed by 45 min reperfusion. BCCAO caused significant depletion in superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and significant increase in lipid peroxidation along with severe neuronal damage in the brain. All the alterations except depletion in glutathione peroxidase and glutathione-S-transferase levels induced by cerebral ischemia were significantly attenuated by 15 days pretreatment with methanolic extract of P. dactylifera fruits (100, 300 mg/kg), whereas 30 mg/kg dose was insignificant in this regard. These results suggest the possible use P. dactylifera against bilateral common carotid artery occlusion induced oxidative stress and neuronal damage.