DSpace

King Saud University Repository >
King Saud University >
COLLEGES >
Health Colleges >
College of Applied Medical Sciences >
College of Applied Medical Sciences >

Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/18581

Title: Carnitine Deficiency Aggravates Cyclophosphamide-Induced Cardiotoxicity in Rats
Authors: G. Fatani, Amal.
Rizwan, Lubna.
M. Aleisa, Abdulaziz.
A. Al-Shabanah, Othman.
M, Mohamed.
Ahmed, Sayed.
Keywords: Cardiomyopathy; D –Carnitine; Carnitine deficiency; Cyclophosphamide; Mildronate; Propionyl- L -carnitine
Issue Date: 2010
Publisher: Chemotherapy
Citation: Chemotherapy 2010;56:71-81
Abstract: Background: This study examined, for the first time, the involvement of carnitine deficiency in cardiotoxicity, particularly cyclophosphamide (CP)-induced cardiomyopathy, as well as effects of carnitine supplementation with propionyl-L -carnitine (PLC) on cardiotoxicity. Methods: An animal model of carnitine deficiency was developed in rats treated with D -carnitine (DC)-mildronate (MD). Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, PLC (250 mg/kg/day), and DC (250 mg/kg/day) combined with MD (200 mg/kg/day), respectively, for 10 successive days. In groups 4–6, the same doses of normal saline, PLC and DC-MD were injected, respectively, during the 5 successive days before and after a single dose of CP (200 mg/kg). On day 6 after CP treatment, 24-hour urine was collected, then animals were sacrificed, and serum as well as hearts were isolated. Results: CP caused a significant increase in serum creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), urinary carnitine excretion and clearance and intramitochondrial acetyl-CoA/CoA-SH, and a significant decrease in serum free carnitine, total carnitine and adenosine triphosphate (ATP) contents in cardiac tissue. In the carnitine-depleted rats, CP induced dramatic increases in CK-MB and LDH levels, carnitine clearance and intramitochondrial acetyl-CoA/CoA-SH, as well as progressive reduction in total carnitine and ATP in cardiac tissues. Interestingly, PLC supplementation completely reversed the biochemical and histopathological changes induced by CP to the control values. Conclusion: (1) Carnitine deficiency is a risk factor which is involved in CP-related cardiomyopathy; (2) serum and urinary carnitine levels should be monitored and viewed as indices of CP-induced multiple organ toxicity, and (3) carnitine supplementation, using PLC, prevents the development of CP-induced cardiotoxicity.
URI: http://hdl.handle.net/123456789/18581
ISSN: 0009-3157
Appears in Collections:College of Applied Medical Sciences

Files in This Item:

File Description SizeFormat
Amal-2.dot38.5 kBUnknownView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

DSpace Software Copyright © 2002-2007 MIT and Hewlett-Packard - Feedback