carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced fanconi syndrome rat model肉碱缺乏症和氧化应激引发毒性ifosfamide-induced fanconi综合征大鼠模型.pdfVIP

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carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced fanconi syndrome rat model肉碱缺乏症和氧化应激引发毒性ifosfamide-induced fanconi综合征大鼠模型.pdf

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carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced fanconi syndrome rat model肉碱缺乏症和氧化应激引发毒性ifosfamide-induced fanconi综合征大鼠模型

ReseARCh pA peR Oxidative Medicine and Cellular Longevity 3:4, 266-274; July/August 2010; © 2010 Landes Bioscience Carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced Fanconi Syndrome rat model Mohamed M. sayed-Ahmed,* Amal Q. Darweesh and Amal J. Fatani Department of pharmacology; College of pharmacy; King saud University; Riyadh, Kingdom of saudi Arabia Key words: ifosfamide, Fanconi Syndrome, carnitine deficiency, cardiotoxicity, D-carnitine, mildronate, propionyl-L-carnitine In addition to hemorrhagic cystitis, Fanconi sy ndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi sy ndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using propionyl-L-carnitine (pLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one