Carnitine Deficiency Provokes Cisplatin-Induced Hepatotoxicity in Rats

Abdulhakeem A. Al-Majed,

Abdulhakeem A. Al-Majed

Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

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Abdulhakeem A. Al-Majed,

Abdulhakeem A. Al-Majed

Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

Search for more papers by this author

First published: 25 January 2007

https://doi.org/10.1111/j.1742-7843.2006.00024.x

Citations: 34

Author for correspondence: Abdulhakeem A. Al-Majed, Department of Pharmacology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia (fax +966 1 467 7200, e-mail [email protected]).

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Abstract

Abstract: This study investigates whether or not carnitine deficiency is a risk factor and could contribute to cisplatin-induced liver toxicity. A total of 60 adult male Wistar albino rats were divided into six groups. The first three groups were injected intraperitoneally with normal saline, propionyl-l-carnitine (500 mg/kg), and d-carnitine (500 mg/kg), respectively, for 10 successive days. The fourth, fifth and sixth groups were injected intraperitoneally with the same doses of normal saline, propionyl-l-carnitine and d-carnitine, respectively, for 5 successive days before and after a single dose of cisplatin (7 mg/kg). Administration of the standard nephrotoxic dose of cisplatin did not produce any changes in serum alanine transaminase and γ-glutamyl transferase and no morphological changes in liver tissues. However, it did produce a significant increase in thiobarbituric acid reactive substances and total nitrate/nitrite and a significant decrease in reduced glutathione content in liver tissues. On the other hand, combined treatment with cisplatin and d-carnitine induced a dramatic increase in serum alanine transaminase and γ-glutamyl transferase, as well as progressive reduction in total carnitine and ATP content in liver tissue. Moreover, histopathological examination of liver tissues confirmed the biochemical data, where cisplatin and d-carnitine combination showed signs of liver injury manifested as focal necro-inflammatory changes and portal inflammation. Interestingly, in carnitine supplemented rats using propionyl-l-carnitine, cisplatin did not produce any biochemical and histopathological changes in liver tissues. In conclusion, data from this study suggest for the first time that (1) carnitine deficiency is a risk factor and could precipitate cisplatin-induced hepatotoxicity, (2) oxidative stress is not the main cause of cisplatin-related hepatotoxicity and (3) propionyl-l-carnitine prevents the development of cisplatin-induced liver injury.

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Volume100, Issue3

March 2007

Pages 145-150

Carnitine Deficiency Provokes Cisplatin-Induced Hepatotoxicity in Rats

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Carnitine Deficiency Provokes Cisplatin-Induced Hepatotoxicity in Rats

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