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Propionyl‐L‐carnitine prevents The Progression of Cisplatin‐Induced Cardiomyopathy in a Carnitine‐Depleted Rat Model
Author(s) -
ALSHABANAH OTHMAN A,
AlMajed Abdulhakeem A,
AlYaha Abdulaziz A,
Aleisa Abdulaziz M,
SayedAhmed Mohamed M,
AlRejaie Salim S
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a234-c
Subject(s) - carnitine , cardiomyopathy , cardiotoxicity , saline , medicine , glutathione , endocrinology , cisplatin , oxidative stress , toxicity , chemistry , pharmacology , chemotherapy , heart failure , enzyme , biochemistry
This study is to investigate whether endogenous carnitine depletion and/or carnitine deficiency is a risk factor during development of cisplatin (CDDP)‐induced cardiomyopathy and if so, whether carnitine supplementation by propionyl‐L‐carnitine (PLC) could offer protection against this toxicity. A total of 60 adult male rats were divided into 6 groups. The first three groups were injected intraperitoneally with normal saline, PLC (500 mg kg ‐1 ), and D‐carnitine (500 mg kg ‐1 ) respectively, for 10 successive days. The 4th, 5th, and 6th groups were injected intraperitoneally with the same doses of normal saline, PLC and D‐carnitine, respectively for 5 successive days before and after a single dose of CDDP (7 mg kg ‐1 ). Six days after CDDP treatment, animals were sacrificed, serum as well as hearts were isolated and analyzed. In the carnitine‐depleted rat model, CDDP induced dramatic increase in serum cardiomyopathy enzymatic indices, CK‐MB and LDH, as well as progressive reduction in total carnitine and ATP content in cardiac tissue. Interestingly, PLC supplementation attenuated CDDP‐induced cardiomyopathy manifested by normalizing the increase of serum CK‐MB and LDH, TBARS and NOx, and the decrease in total carnitine, GSH and ATP content in cardiac tissues. In conclusion, data from this study suggest for the first time that carnitine deficiency and oxidative stress are risk factors and should be viewed as mechanisms during development of CDDP‐related cardiomyopathy and that carnitine supplementation, using PLC, prevents the progression of CDDP‐induced cardiotoxicity.