Carnitine Deficiency Provokes Cisplatin‐Induced Hepatotoxicity in Rats

Abstract

This study investigates whether or not carnitine deficiency is a risk factor and could contribute to cisplatininduced 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--carnitine (500 mg/kg), and -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--carnitine and -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 -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 -carnitine combination showed signs of liver injury manifested as focal necro-inflammatory changes and portal inflammation. Interestingly, in carnitine supplemented rats using propionyl--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--carnitine prevents the development of cisplatin-induced liver injury.

Dose-Dependent Protective Effect of L-Carnitine on Oxidative Stress in the Livers of Hyperthyroid Rats

“…Endogenous L-carnitine is synthesized from lysine and methi- onine primarily in the liver, as well as in the kidneys and brain tissue [24]. Previous studies have indicated that L-carnitine has an important role in oxidative/antioxidative balance as well as in the transport function of long-chain fatty acids into the mitochondria in biological systems [12][13][14][15]. However, the effects of L-carnitine on specific antioxidant enzymes, such as GPX, CAT and MPO, which detoxify H 2 O 2 in water, have been reported independently in a few studies [14,25].…”

“…L-carnitine inhibits both the mitochondrial damage induced by oxidative stress and mitochondria-dependent apoptosis in various types of cells [12,13]. Recent studies suggest that L-carnitine may play an important role in oxidative/antioxidative balance and has an antiperoxidative effect on several tissues [14][15][16].…”

Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats

“…injection of CDDP (7 mg kg −1 ). The doses of CDDP and L-carnitine used in this study were selected in accordance with Al-Majed [13].…”

“…It is synthesized endogenously from the essential amino acids lysine and methionine. In fact, carnitine effectively inhibits mitochondrial damage induced by oxidative stress, as well as mitochondriadependent apoptosis in various types of cells [13,14]. The effects of LC on the metabolism of tissues in organs such as the heart [15], brain [16], and liver [13] have been studied widely.…”

“…In fact, carnitine effectively inhibits mitochondrial damage induced by oxidative stress, as well as mitochondriadependent apoptosis in various types of cells [13,14]. The effects of LC on the metabolism of tissues in organs such as the heart [15], brain [16], and liver [13] have been studied widely. Current reports suggest that LC may play a significant role in balancing antioxidative systems and has an antiperoxidative effect on some tissues [17,18].…”