Ameliorative effect of flunarizine in cisplatin-induced acute renal failure via mitochondrial permeability transition pore inactivation in rats
| Autor: | Sumeet Kumar Singla, Jai Singh, Shailja Sood, Amandeep Singh, Ajay Rana, Atinderjeet Singh, Arunachalam Muthuraman |
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| Rok vydání: | 2010 |
| Předmět: |
Fractional excretion of sodium
Renal function Pharmacology Kidney Mitochondrial Membrane Transport Proteins Thiobarbituric Acid Reactive Substances Blood Urea Nitrogen Nephrotoxicity Electron Transport Complex IV Rats Sprague-Dawley chemistry.chemical_compound Adenosine Triphosphate Acetylglucosaminidase medicine Animals Flunarizine Blood urea nitrogen Creatinine Mitochondrial Permeability Transition Pore Body Weight Sodium General Medicine Acute Kidney Injury Glutathione Mitochondria Rats medicine.anatomical_structure Mitochondrial permeability transition pore chemistry Anesthesia Cyclosporine Calcium Female Cisplatin medicine.drug |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 383:57-64 |
| ISSN: | 1432-1912 0028-1298 |
| DOI: | 10.1007/s00210-010-0572-z |
| Popis: | This study was aimed to evaluate the protective effect of flunarizine on cisplatin-induced acute renal failure. Administration of cisplatin (6 mg/kg, i.p. on day 6) significantly increased serum blood urea nitrogen and creatinine, urinary N-acetyl β-d-glucosaminidase, tissue thiobarbituric acid reactive substances and total calcium whereas, decreased body weight, fractional excretion of sodium, creatinine clearance tissue-reduced glutathione, mitochondrial cytochrome c oxidase, and ATP levels were observed in acute renal failure rats. Moreover, cisplatin produced histopathological changes in the renal tissue. Furthermore, flunarizine (100, 200, and 300 μM/kg, p.o., for six consecutive days) was administered to evaluate its therapeutic potential in acute renal failure, and the results were compared with cylclosporin A (50 μM/kg, p.o., for six consecutive days) as a reference drug. Flunarizine resulted in the attenuation of cisplatin-induced renal dysfunction, oxidative stress marker, mitochondrial damage, and histopathological changes in rats. Medium and higher doses of flunarizine produced significant renal protective effect which was comparable to cyclosporin A. The results of this study clearly revealed that flunarizine protected the kidney against the nephrotoxic effect of cisplatin via mitochondrial permeability transition pore inactivation potential. |
| Databáze: | OpenAIRE |
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