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Carnitine Deficiency Provokes Cisplatin‐Induced Hepatotoxicity in Rats
Author(s) -
AlMajed Abdulhakeem A.
Publication year - 2007
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2006.00024.x
Subject(s) - carnitine , glutathione , aspartate transaminase , cisplatin , toxicity , endocrinology , alanine transaminase , medicine , saline , chemistry , nephrotoxicity , transaminase , pharmacology , biochemistry , enzyme , chemotherapy , alkaline phosphatase
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.