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Can Trimetazidine, Vinpocetine or Isosorbide Dinitrate Ameliorate Cyclosporine-Induced Nephrotoxicity in Rats?
並列摘要
BACKGROUND: The present study was conducted to investigate the effect of concurrent administration of trimetazidine (a mitochondrial stabilizing anti-anginal agent), vinpocetine (a phosphodiesterase-1 inhibitor) and isosorbide dinitrate (a NO donor) on nephrotoxicity induced by cyclosporine A (CsA) treatment. METHODS: Female albino rats were divided into eight groups. Group1 rats were treated with corn oil and served as normal control. Group2 received CsA (15mg/kg, s.c. for 4 weeks) and served as control. Groups 3 and 4 received CsA along with trimetazidine (5 &10mg/kg, p.o). Groups 5 and 6 received CsA along with vinpocetine (5 &10mg/kg, p.o). Groups 7 and 8 received CsA along with isosorbide dinitrate (3.6, and 7.2mg/kg p.o). Blood urea nitrogen (BUN), serum creatinine, serum uric acid and blood glucose were measured. Creatinine clearance (C_(cr)) and proteinuria were estimated. Reduced glutathione (GSH), lipid peroxides, nitric oxide (NO), and hydroxyproline contents were measured in kidney tissues. RESULTS: Injection of CsA increased BUN, serum creatinine, and blood glucose levels as well as renal hydroxyproline content. It also decreased C_(cr) and renal NO content. Only isosorbide dinitrate (3.6mg/kg) could partially improve CsA-dependent changes in renal function as shown by decrease in elevated serum creatinine and renal hydroxyproline content as well as improvement of C_(cr). However, administration of isosorbide dinitrate at a higher dose (7.2mg/kg) along with CsA deteriorated the renal function reflected by decreased C_(cr) and renal NO content associated with proteinuria, increased BUN and uric acid levels. CONCLUSION: The current study demonstrates that isosorbide dinitrate at the dose of 3.6mg/kg could protect against CsAinduced nephrotoxicity, whereas both trimetazidine and vinpocetine are of unclear utility.
延伸閱讀
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