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  3. Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1-PGC-1α pathway activation

Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1-PGC-1α pathway activation

  • Ecotoxicol Environ Saf. 2022 Sep 1;242:113879. doi: 10.1016/j.ecoenv.2022.113879.
Wenxuan Dong 1,  Lianqi Yan 2,  Yun Tan 1,  Shufang Chen 3,  Kanglei Zhang 1,  Zhonggui Gong 1,  Wenjing Liu 1,  Hui Zou 1,  Ruilong Song 1,  Jiaqiao Zhu 1,  Gang Liu 4,  Zongping Liu 5
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou 225009, People's Republic of China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, People's Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People's Republic of China.
  • 2 Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, People's Republic of China; Department of Orthopedics,　Clinical Medical College of Yangzhou University, Subai People's Hospital, Yangzhou, Jiangsu 225009, People's Republic of China.
  • 3 Ningbo Academy of Agricultural Sciences, Ningbo 315040, People's Republic of China.
  • 4 College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou 225009, People's Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People's Republic of China; Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA. Electronic address: [email protected].
  • 5 College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou 225009, People's Republic of China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, People's Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People's Republic of China. Electronic address: [email protected].
PMID: 35841654 DOI: 10.1016/j.ecoenv.2022.113879
Abstract

Melatonin is an indoleamine produced in the pineal gland and has many physiological roles. There is increasing evidence that melatonin ameliorates cadmium (Cd)-induced nephrotoxicity. The potential protective impact of melatonin against Cd-induced nephrotoxicity and the mechanisms behind this protection are unknown. The relevance of mitochondrial dynamics in Cd-induced nephrotoxicity and the putative mechanism of melatonin-mediated protection were examined in this study. We show that melatonin prevents Cd-induced nephrotoxicity by inhibiting dynamin-related protein 1 (Drp1)- and mitochondrial fission protein 1 (Fis1)-mediated mitochondrial fission. Melatonin treatment attenuated cytotoxicity, suppressed oxidative stress, restored mitochondrial membrane potential, and increased mitochondrial mass in response to Cd exposure. Consistent with this finding, melatonin treatment increased Cd-inhibited Sirtuin 1 (SIRT1) and Peroxisome Proliferator-activated Receptor gamma coactivator 1 alpha (PGC-1α) expression and inhibited Drp1- and Fis1-mediated mitochondrial fission. Like melatonin, SIRT1 overexpression via resveratrol attenuated Drp1- and Fis1-mediated mitochondrial fission and other Cd-induced mitochondrial oxidative injuries effectively. Melatonin has significant pharmacological potential for protecting against Cd-induced nephrotoxicity by preventing excessive mitochondrial fission.

Keywords

Cadmium; Melatonin; Mitochondrial fission; PGC‐1α; SIRT1.

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