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

BMB Rep. 2021 Nov;54(11):575-580. doi: 10.5483/BMBRep.2021.54.11.132.

Abstract

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagyrelated proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-weekold male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration. [BMB Reports 2021; 54(11): 575-580].

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Autophagy*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Cisplatin / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology
  • Phosphorylation
  • Rats
  • Rats, Wistar

Substances

  • Antineoplastic Agents
  • Autophagy-Related Proteins
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Cisplatin