Progression of Cisplatin-Induced Nephrotoxicity in a Carnitine-Depleted Rat Model

<i>Background:</i> This study has been initiated to investigate whether endogenous carnitine depletion and/or carnitine deficiency is an additional risk factor and/or a mechanism in cisplatin-induced nephrotoxicity and to gain insights into the possibility of a mechanism-based protection by <i>L</i>-carnitine against this toxicity. <i>Methods:</i> 60 male Sprague-Dawley rats were divided into six groups of 10 animals each and received one of the following treatments: The first three groups were injected intraperitoneally with normal saline, <i>L</i>-carnitine (500 mg/kg), and <i>D</i>-carnitine (750 mg/kg), respectively, for 10 successive days. The 4th, 5th, and 6th groups were injected intraperitoneally with the same doses of normal saline, <i>L</i>-carnitine and <i>D</i>-carnitine, respectively, for 5 successive days before and after a single dose of cisplatin (7 mg/kg). Six days after cisplatin treatment, the animals were sacrificed, and serum as well as kidneys were isolated and analyzed. <i>Results:</i> A single dose of cisplatin resulted in a significant increase in blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) and nitric oxide (NO) and a significant decrease in total carnitine, reduced glutathione (GSH) and adenosine triphosphate (ATP) content in kidney tissues. Interestingly, <i>L</i>-carnitine supplementation attenuated cisplatin-induced nephrotoxicity manifested by normalizing the increase of serum creatinine, BUN, MDA and NO and the decrease in total carnitine, GSH and ATP content in kidney tissues. In the carnitine-depleted rat model, cisplatin induced a progressive increase in serum creatinine and BUN as well as a progressive reduction in total carnitine and ATP content in kidney tissue. Histopathological examination of kidney tissues confirmed the biochemical data, i.e. <i>L</i>-carnitine supplementation protected against cisplatin-induced kidney damage, whereas <i>D</i>-carnitine aggravated cisplatin-induced renal injury. <i>Conclusion:</i> Data from this study suggest that: (1) oxidative stress plays an important role in cisplatin-induced kidney damage; (2) carnitine deficiency should be viewed as an additional risk factor and/or a mechanism in cisplatin-induced renal dysfunction, and (3) <i>L</i>-carnitine supplementation attenuates cisplatin-induced renal dysfunction.