Inhibition of Gene Expression of Organic CationCarnitine Transporter and Antioxidant Enzymes in Oxazaphosphorines-Induced Acute Cardiomyopathic Rat Models
Joint Authors
Sayed-Ahmed, Mohammed M.
Hafez, Mohamed M.
Aldelemy, Meshan Lafi
al-Shabanah, Othman A.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-05-30
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
It is well documented that high therapeutic doses of oxazaphosphorines, cyclophosphamide (CP) and ifosfamide (IFO), are associated with cardiomyopathy.
This study investigated whether oxazaphosphorines alter the expression of organic cation/carnitine transporter (OCTN2) and antioxidant genes and if so, whether these alterations contribute to CP and IFO-induced cardiotoxicity.
Adult male Wistar albino rats were assigned to one of six treatment groups namely, control, L carnitine, CP, IFO, CP plus L carnitine and IFO plus L carnitine.
In cardiac and kidney tissues, CP and IFO significantly decreased mRNA and protein expression of OCTN2.
Oxazaphosphorines significantly increased serum acyl-carnitine/free carnitine ratio and urinary carnitine excretion and significantly decreased total carnitine in cardiac tissues.
Interestingly, carnitine supplementation completely reversed the biochemical and gene expression changes-induced by oxazaphosphorines to the control values, except OCTN2 expression remained inhibited by IFO.
Data from this study suggest that: (1) Oxazaphosphorines decreased myocardial carnitine content following the inhibition of OCTN2 mRNA and protein expression in cardiac tissues.
(2) Oxazaphosphorine therapy increased urinary loss of carnitine secondary to the inhibition of OCTN2 mRNA and protein expression in proximal tubules of the kidney.
(3) Carnitine supplementation attenuates CP but not IFO-induced inhibition of OCTN2 mRNA and protein expression in heart and kidney tissues.
American Psychological Association (APA)
Sayed-Ahmed, Mohammed M.& Aldelemy, Meshan Lafi& Hafez, Mohamed M.& al-Shabanah, Othman A.. 2012. Inhibition of Gene Expression of Organic CationCarnitine Transporter and Antioxidant Enzymes in Oxazaphosphorines-Induced Acute Cardiomyopathic Rat Models. Oxidative Medicine and Cellular Longevity،Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-472754
Modern Language Association (MLA)
Sayed-Ahmed, Mohammed M.…[et al.]. Inhibition of Gene Expression of Organic CationCarnitine Transporter and Antioxidant Enzymes in Oxazaphosphorines-Induced Acute Cardiomyopathic Rat Models. Oxidative Medicine and Cellular Longevity No. 2012 (2012), pp.1-13.
https://search.emarefa.net/detail/BIM-472754
American Medical Association (AMA)
Sayed-Ahmed, Mohammed M.& Aldelemy, Meshan Lafi& Hafez, Mohamed M.& al-Shabanah, Othman A.. Inhibition of Gene Expression of Organic CationCarnitine Transporter and Antioxidant Enzymes in Oxazaphosphorines-Induced Acute Cardiomyopathic Rat Models. Oxidative Medicine and Cellular Longevity. 2012. Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-472754
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-472754