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Effects of cisplatin on mitochondrial function and autophagy-related proteins in skeletal muscle of rats
Dae Yun Seo 1,# (Dr.), Jun Hyun Bae 2,5,# (Dr.), Didi Zhang3 (Dr.), Wook Song 2,4 (Prof.), Hyo-Bum Kwak 5 (Prof.), Jun-Won Heo 5 (MS), Su-Jeen Jung6 (Prof.), Hyeong Rok Yun1 (Dr.), Tae Nyun Kim 1 (Prof.), Sang Ho Lee7 (Prof.), Amy Hyein Kim1 (MS), Dae Hoon Jeong8 (Prof.), Hyoung Kyu Kim1 (Prof.), Jin Han1,* (Prof.)
1Department of Physiology, College of Medicine, Inje University, National Research Laboratory for Mitochondrial Signaling, Smart Marine Therapeutics Center, Cardiovascular and Metabolic Disease Center,
2Health & Exercise Science Laboratory, Seoul National University, Institute of Sports Science,
3School of Physical Education, Xiang Minzu University,
4Seoul National University, Institute of Aging,
5Department of Kinesiology, Inha University,
6Department of Leisure Sports, Seoil University,
7Department of Taekwondo, Dong-A University,
8Department of Obstetrics and Gynecology, College of Medicine, Inje University, Busan Paik Hospital
Abstract
Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagy-related proteins 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-week-old 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 giv-en 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 pro-teins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration.
Abstract, Accepted Manuscript(in press) [Submitted on September 16, 2021, Accepted on October 14, 2021]
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