1. The role of mitochondrial dynamics imbalance in hexavalent chromium-induced apoptosis and autophagy in rat testis.
- Author
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Wang, Ruonan, Huang, Yuxiang, Yu, Lu, Li, Siyu, Li, Jiayi, Han, Biqi, Zheng, Xiaoyan, and Zhang, Zhigang
- Subjects
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BAX protein , *TESTIS , *POLLUTANTS , *MITOCHONDRIA , *AUTOPHAGY , *SPERMATOGENESIS - Abstract
Hexavalent chromium (Cr(VI)) is a ubiquitous environmental pollutant that can cause reproductive toxicity. However, the exact mechanism of Cr(VI)-induced testis toxicity remains largely elusive. This study aims to explore the possible molecular mechanism of Cr(VI)-provoked testicular toxicity. Male Wistar rats were intraperitoneally injected with 0, 2, 4, or 6 mg/kg body weight/day of potassium dichromate (K 2 Cr 2 O 7), respectively, for 5 weeks. The results revealed that Cr(VI)-treated rat testis presented varying degrees of damage in a dose-dependent manner. Concretely, Cr(VI) administration suppressed Sirtuin 1/Peroxisome proliferator-activated receptor-γ coactivator-1α pathway and led to mitochondrial dynamics disorder, along with the elevation of mitochondrial division and the repression of mitochondrial fusion. Meanwhile, the downstream effector of Sirt1, nuclear factor-erythroid-2-related factor 2 (Nrf2), was downregulated, and correspondingly exacerbated oxidative stress. Mitochondrial dynamics disorder and Nrf2 inhibition collectively contribute to abnormal mitochondrial dynamics in testis, which further promotes apoptosis and autophagy, evidenced by dose-dependently increasing the protein levels and gene expressions of apoptosis-related (including Bcl-2-associated X protein, cytochrome c , and cleaved-caspase 3) and autophagy-related (Beclin-1, ATG4B, and ATG5). Collectively, our results demonstrate that Cr(VI) exposure induced testis apoptosis and autophagy by disrupting the balance of mitochondrial dynamics and the oxidation-reduction process in rats. • K 2 Cr 2 O 7 induces mitochondrial dynamics disorder in rat testis by inhibiting Sirt1/PGC-1α axis. • K 2 Cr 2 O 7 exposure aggravates inhibition of Nrf2 pathway and promotes oxidative stress. • K 2 Cr 2 O 7 exposure promotes apoptosis and autophagy, leading to testicular damage. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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