Resveratrol alleviates Mono-2-ethylhexyl phthalate-induced mitophagy, ferroptosis, and immunological dysfunction in grass carp hepatocytes by regulating the Nrf2 pathway

  • J Environ Manage. 2024 Dec:371:123235. doi: 10.1016/j.jenvman.2024.123235.
Xiaodan Wang  1 ,  Meichen Gao  1 ,  Xiunan Lu  1 ,  Yutian Lei  1 ,  Jiatong Sun  1 ,  Mengyao Ren  1 ,  Tong Xu  2 ,  Hongjin Lin  3
Affiliations
  • 1. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
  • 2. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China. Electronic address: [email protected].
  • 3. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Laboratory of Embryo Biotechnology, College of Life Science, Northeast Agricultural University, Harbin, 150030, China. Electronic address: [email protected].
PMID: 39509968 DOI: 10.1016/j.jenvman.2024.123235
Abstract

Mono-2-ethylhexyl phthalate (MEHP) is the major biologically active metabolite of Di(2-ethylhexyl) phthalate (DEHP). This MEHP mono-ester metabolite can be transported through the bloodstream into tissues such as the liver, kidneys, fat, and testes and cause corresponding damage. Resveratrol (RSV) has anti-inflammatory, antioxidant, and detoxification characteristics. Our research examined whether RSV alleviates MEHP-induced grass carp hepatocyte (L8824 cell) injury and its relationship with the Nrf2 pathway, Mitophagy, Ferroptosis, and immune function. Therefore, we treated L8824 cells with 85 μM MEHP and/or 2 μM RSV. The findings indicated that exposing MEHP resulted in increased Reactive Oxygen Species (ROS) content and decreased mitochondrial membrane potential in L8824 cells, which induced an up-regulation of the expression of mitophagy-related indicators (PINK1, Parkin, Beclin1, LC3B, and ATG5) and a down-regulation of p62. An up-regulation of the expression of the ferroptosis-related indicators TFR1 and COX-2, and GPX4 and FTH expression was down-regulated. In addition, there was a decrease in the expression of IL-2 and IFN-γ and an increase in the expression of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 after exposure to MEHP. RSV activates the Nrf2 pathway and effectively alleviates MEHP-induced Mitophagy, Ferroptosis, and immunologic dysfunction of L8824 cells.

Keywords
Ferroptosis; Immune dysfunction; L8824 cells; MEHP; Mitophagy; Nrf2; Resveratrol.
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