Benzo[a]pyrene exposure in muscle triggers sarcopenia through aryl hydrocarbon receptor-mediated reactive oxygen species production

Shou En Wu, Ju Chun Hsu, Yung Lung Chang, Hsiao Chi Chuang, Yi Lin Chiu, Wei Liang Chen

研究成果: 雜誌貢獻文章同行評審


Background: Benzo[a]pyrene (BaP), a toxic carcinogen, is associated with various adverse effects but is rarely discussed in muscle-related disorders. This study investigated in vitro and in vivo effects triggered by BaP exposure in muscles and hypothesized that exposure might induce conditions similar to sarcopenia due to the shared mechanism of oxidative stress. In vitro experiments used C2C12 mouse myoblasts to examine effects induced by BaP exposure in control (untreated) and BaP-treated (10 µM/ml) muscle cells. An established TNF-α-treated sarcopenia model was utilized to verify our results. In vivo experiments compared immunohistochemical staining of sarcopenia-related markers in rats exposed to clean air and polluted air. Results: In C2C12 cells, after 2–72 h of BaP exposure, elevated mRNA and protein expressions were observed in aryl hydrocarbon receptor (AhR) and cytochrome P450 1A1, subsequently in ROS (NOX2 and NOX4) production, inflammatory cytokines (IL-6, TNF-α, and NF-kB), and proteins mediating apoptotic cell death (caspase-3 and PARP). Two myokines also altered mRNA and protein expressions akin to changes in sarcopenia, namely decreased irisin levels and increased myostatin levels. In addition, N-acetylcysteine, a well-known antioxidant, led to decrease in oxidative markers induced by BaP. The validation by TNF-α-treated sarcopenia model revealed comparable biological responses in either TNF-α or BaP treated C2C12 cells. In vivo experiments with rats exposed to air pollution showed increased expression of BaP, AhR, 8-hydroxydeoxyguanosine, and myostatin and decreased irisin expression in immunohistochemical staining. Conclusions: Our results suggest that BaP exerts deleterious effects on the muscle, leading to conditions indicative of sarcopenia. Antioxidant supplementation may be a treatment option for BaP-induced sarcopenia, but further validation studies are needed.
期刊Ecotoxicology and Environmental Safety
出版狀態已發佈 - 7月 2022

ASJC Scopus subject areas

  • 污染
  • 公共衛生、環境和職業健康
  • 健康、毒理學和誘變


深入研究「Benzo[a]pyrene exposure in muscle triggers sarcopenia through aryl hydrocarbon receptor-mediated reactive oxygen species production」主題。共同形成了獨特的指紋。