CDP-choline circumvents mercury-induced mitochondrial damage and renal dysfunction

Abstract

Heavy metal ions are known to produce harmful alterations on kidney function. Specifically, the accumulation of Hg²⁺ in kidney tissue may induce renal failure. In this work, the protective effect of CDP-choline against the deleterious effects induced by Hg²⁺ on renal function was studied. CDP-choline administered ip at a dose of 125 mg/kg body weight prevented the damage induced by Hg²⁺ administration at a dose of 3 mg/kg body weight. The findings indicate that CDP-choline guards mitochondria against Hg²⁺ -toxicity by preserving their ability to retain matrix content, such as accumulated Ca²⁺ . This nucleotide also protected mitochondria from Hg²⁺ -induced loss of the transmembrane electric gradient and from the generation of hydrogen peroxide and membrane TBARS. In addition, CDP-choline avoided the oxidative damage of mtDNA and inhibited the release of the interleukins IL-1 and IL6, recognized as markers of acute inflammatory reaction. After the administration of Hg²⁺ and CDP, CDP-choline maintained nearly normal levels of renal function and creatinine clearance, as well as blood urea nitrogen (BUN) and serum creatinine.

Keywords: kidney dysfunction; mercury; mitochondria; permeability transition.