Comparative studies on protective efficacy of gentisic acid and 2-pyrocatechuic acid against 5-fluorouracil induced nephrotoxicity in Wistar rats

241-247Nephrotoxicity 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

Comparative studies on protective efficacy of gentisic acid and 2-pyrocatechuic acid against 5-fluorouracil induced nephrotoxicity in Wistar rats

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

Neuroprotective and antioxidant role of Phoenix dactylifera in permanent bilateral common carotid occlusion in rats

Objective: To investigate neuroprotective and antioxidant effect of Phoenix dactylifera (P. dactylifera) (PD) fruits. Methods: Methanolic extract of P. dactylifera fruits (MEPD) at doses of 30, 100 and 300 mg/kg was studied against permanent BCCAO (long-term hypoperfusion) in rats. Chronic occlusion of bilateral common carotid arteries (BCCA) caused significant elevation in malondialdehyde levels due to increased lipid peroxidation as well as decrease in levels of other biochemical enzymes i.e. glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferse, catalase and superoxide dismutase. Results: Post occlusion treatment for 15 d with 100 and 300 mg/kg doses of MEPD significantly reduced the enhanced malondialdehyde levels and reversed the alterations in the declined levels of antioxidant enzymes in brain homogenates of hypoperfused rats. Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and restlessness (open field paradigm) accompanied by deficits of spatial learning and memory (Morris water maze testing). Additionally, histopathological observations in hypoperfused brains revealed reactive changes like shrinkage and necrosis of neurons. 100 and 300 mg/kg doses of MEPD significantly alleviated these alterations. Conclusions: These results confirmed the protective role of P. dactylifera in ischemia hypoperfusion and thereby it's beneficial role in cerebrovascular insufficiency states and related complications

Evaluation of antioxidant and neuroprotective effect of date palm (<i style="">Phoenix dactylifera </i>L.) against bilateral common carotid artery occlusion in rats

627-633The 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 damag

DESIGN AND STATISTICAL OPTIMIZATION OF ANTACID ANALGESIC EFFERVESCENT TABLETS BY USING 2^3 FACTORIAL DESIGN

Objective: The present research work was undertaken with an aim to formulate a combination dosage form constituting an antacid and analgesic which may be useful in case of hyperacidity associated headache.Methods: In this formulation, a mixture of magnesium and aluminium hydroxide was used as the antacid. Ibuprofen was used as analgesic drug while, citric acid and tartaric acid along with sodium bicarbonate were used as effervescent mixture. The prepared tablets of all the formulations were evaluated for physical characterization.Results: The infra red spectra revealed that there was no chemical interaction between the drug and excipients which showed their compatibility. The results of these studies were found to be within the standard Pharmacopoeial limits. The release character was studied using the disintegration and dissolution studies conducted. The results of 23 factorial design revealed that the amounts of crosspovidone, tartaric acid and citric acid used in effervescent formulation significantly affected the dependent variables i. e. Hardness, friability and disintegration time etc. The stability studies of the tablet formulation showed that the tablets remained stable even after exposing to stress condition of temperatures.Conclusion: It was thus concluded that by adopting a systematic formulation approach, optimized release mechanism can be reached in the shortest time with minimum efforts.Â