Combined Administration of l-Carnitine and Ascorbic Acid Ameliorates Cisplatin-Induced Nephrotoxicity in Rats

ABSTRACT

Objectives: Cisplatin (CIS) is an effective antitumor drug. However, its clinical use is limited due to nephrotoxicity. l-Carnitine and vitamin C are both natural antioxidant that can be obtained from diets. This study investigated the effects of l-carnitine and/or vitamin C in rats against cisplatin-induced nephrotoxicity.

Methods: Twenty-five male Wistar rats were divided into 5 groups of 5 rats each. Group 1, normal control. Group 2, positive control, received cisplatin (10 mg/kg/day intraperitoneally [i.p.]) for 3 days. Groups 3, 4, and 5 received cisplatin for 3 days and thereafter l-carnitine (50 mg/kg/day), vitamin C (100 mg/kg/day), or their combination, respectively, for 28 days. At the end of the study, a biochemical study was carried out in which nephrotoxicity markers, electrolytes, hematological indices, oxidative stress biomarkers, and renal histopathological alterations were evaluated.

Results: CIS-treated rats developed significant polyuria, increase in the plasma levels of creatinine, urea, and inorganic phosphate (P_i), alteration in hematological parameters, and decrease in plasma levels of Na⁺, Cl⁻, K⁺, Ca²⁺, and Mg²⁺. Measurements of 24-hour urine output demonstrated markedly decreased creatinine and urea and increased Na⁺, Cl⁻, K⁺, Ca²⁺, and Mg²⁺ levels in the CIS-treated group, whereas P_i levels were not changed. It also caused significantly decreased catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) levels in the rats' kidneys. Histopathological scores revealed renal tubular damage in CIS-treated rats. However, l-carnitine, vitamin C, or their combination significantly attenuated the alterations caused by CIS in the plasma and kidneys of the rats.

Conclusion: l-Carnitine and vitamin C administration ameliorated CIS-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.

KEYWORDS:

• Antioxidant
• ascorbic acid
• l-carnitine
• cisplatin
• creatinine
• oxidative stress