Exploring the Potential of Flunarizine for Cisplatin-Induced Painful Uremic Neuropathy in Rats
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Purpose: The present study was designed to explore the potential of flunarizine for cisplatin induced painful uremic neuropathy in rats. Methods: Cisplatin (2 mg/kg; i.p., for 5 consecutive days) was administered and renal uremic markers i.e., serum creatinine were estimated on days 4 and 25. Behavioral changes were assessed in terms of thermal hyperalgesia (hot plate, plantar, tail immersion,and tail flick tests at different time intervals). Biochemical analysis of total calcium, superoxide anion, DNA, and transketolase,and myeloperoxidase activity in tissue samples was also performed. Furthermore, flunarizine (100, 200, and 300 μM/kg; p.o., for 21 consecutive days) was administered to evaluate its potency on uremic neuropathy, and the results were compared with those for the carbamazepine-treated (30 mg/kg; p.o., for 21 consecutive days) groups. Results: Flunarizine attenuated the cisplatin-induced uremic neuropathy, and the degree of behavioral and biochemical changes in serum and tissue samples in a dose dependent manner. The medium and high doses of flunarizine were shown to produce a significant effect on cisplatin induced painful uremic neuropathy. Conclusions: Our results indicate the potential of flunarizine for anti-oxidative, anti-inflammatory, and neuroprotective actions. Therefore, it may have use as a novel therapeutic agent for the management of painful uremic neuropathy.
Abstract
Purpose: The present study was designed to explore the potential of flunarizine for cisplatin induced painful uremic neuropathy in rats. Methods: Cisplatin (2 mg/kg; i.p., for 5 consecutive days) was administered and renal uremic markers i.e., serum creatinine were estimated on days 4 and 25. Behavioral changes were assessed in terms of thermal hyperalgesia (hot plate, plantar, tail immersion,and tail flick tests at different time intervals). Biochemical analysis of total calcium, superoxide anion, DNA, and transketolase,and myeloperoxidase activity in tissue samples was also performed. Furthermore, flunarizine (100, 200, and 300 μM/kg; p.o., for 21 consecutive days) was administered to evaluate its potency on uremic neuropathy, and the results were compared with those for the carbamazepine-treated (30 mg/kg; p.o., for 21 consecutive days) groups. Results: Flunarizine attenuated the cisplatin-induced uremic neuropathy, and the degree of behavioral and biochemical changes in serum and tissue samples in a dose dependent manner. The medium and high doses of flunarizine were shown to produce a significant effect on cisplatin induced painful uremic neuropathy. Conclusions: Our results indicate the potential of flunarizine for anti-oxidative, anti-inflammatory, and neuroprotective actions. Therefore, it may have use as a novel therapeutic agent for the management of painful uremic neuropathy.
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