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Effects of cisplatin on mitochondrial function and autophagy-related proteins in skeletal muscle of rats

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Cisplatin is widely known as an anti-cancer drug. However,the effects of cisplatin on mitochondrial function and autophagyrelatedproteins levels in the skeletal muscle are unclear. Thepurpose of this study was to investigate the effect of differentdoses of cisplatin on mitochondrial function and autophagy-relatedprotein levels in the skeletal muscle of rats. Eight-weekoldmale Wistar rats (n = 24) were assigned to one of threegroups; the first group was administered a saline placebo (CON,n = 10), and the second and third groups were given 0.1mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8)of cisplatin, respectively. The group that had been administered0.5 mg cisplatin exhibited a reduced BW, skeletal muscletissue weight, and mitochondrial function and upregulated levelsof autophagy-related proteins, including LC3II, Beclin 1, andBNIP3. Moreover, this group had a high LC3 II/I ratio in theskeletal muscle; i.e., the administration of a high dose of cisplatindecreased the muscle mass and mitochondrial functionand increased the levels of autophagy-related proteins. Theseresults, thus, suggest that reducing mitochondrial dysfunctionand autophagy pathways may be important for preventing skeletalmuscle atrophy following cisplatin administration.

Abstract

Cisplatin is widely known as an anti-cancer drug. However,the effects of cisplatin on mitochondrial function and autophagyrelatedproteins levels in the skeletal muscle are unclear. Thepurpose of this study was to investigate the effect of differentdoses of cisplatin on mitochondrial function and autophagy-relatedprotein levels in the skeletal muscle of rats. Eight-weekoldmale Wistar rats (n = 24) were assigned to one of threegroups; the first group was administered a saline placebo (CON,n = 10), and the second and third groups were given 0.1mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8)of cisplatin, respectively. The group that had been administered0.5 mg cisplatin exhibited a reduced BW, skeletal muscletissue weight, and mitochondrial function and upregulated levelsof autophagy-related proteins, including LC3II, Beclin 1, andBNIP3. Moreover, this group had a high LC3 II/I ratio in theskeletal muscle; i.e., the administration of a high dose of cisplatindecreased the muscle mass and mitochondrial functionand increased the levels of autophagy-related proteins. Theseresults, thus, suggest that reducing mitochondrial dysfunctionand autophagy pathways may be important for preventing skeletalmuscle atrophy following cisplatin administration.

참고문헌 (40)

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