L-Carnitine inhibits cisplatin-induced injury of the kidney and small intestine.
Although cis-diamminedichloroplatinum (II) (cisplatin) is a potent anticancer drug, clinical use of this agent is highly limited predominantly because of its strong side effects on the kidney and gastrointestinal tracts. We found that cisplatin impaired respiratory function and DNA of mitochondria in renal proximal tubules and small intestinal mucosal cells, thereby inducing apoptosis of epithelial cells. Cisplatin-induced mitochondrial dysfunction and DNA (mtDNA) injury, lipid peroxidation, and apoptosis of epithelial cells in the kidney and small intestine were strongly inhibited by L-carnitine. However, carnitine had no appreciable effect on the tumoricidal action of cisplatin against cancer cells inoculated in the peritoneal cavity. These results indicate that L-carnitine may have therapeutic potential for inhibiting the side effects of cisplatin and other anticancer agents in the kidney and small intestine.
Chang
BaoJun
B
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan.
Nishikawa
Manabu
M
Sato
Eisuke
E
Utsumi
Kozo
K
Inoue
Masayasu
M
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis; D002331:Carnitine / Q000494:pharmacology*; D002945:Cisplatin / Q000009:adverse effects / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D004247:DNA; D002945:Cisplatin; D002331:Carnitine