Mitochondrial homeostatic imbalance-mediated developmental toxicity to H2S in embryonic zebrafish

Abstract

Hydrogen sulfide (H₂S) is a pervasive environmental and industrial pollutant that poses a substantial threat to human health. Even short-term exposure to H₂S can result in severe respiratory and neurological damage. However, the underlying mechanisms of its biotoxicity remain unclear. Our study demonstrated that continuous exposure to 30 μM (1.02 ppm), whin environmentally H₂S concentration range, results in notable developmental toxicity, including high mortality rates, morphological deformities, and behavioral abnormalities, in zebrafish larvae. Through transcriptomic analysis, examination of mitochondrial structure and function, and tissue and cellular staining, we found that H₂S exposure disrupted mitochondrial dynamics, autophagy, and biogenesis, leading to an imbalance in mitochondrial homeostasis. This disruption induced oxidative stress and extensive apoptosis. Nitric oxide (NO) is a multifunctional signaling molecule known to target and regulate mitochondrial regeneration. In our study, we discovered that sodium nitroprusside (SNP), an NO donor, can activate the NO-sGC-cGMP signaling pathway. This activation improves the homeostatic regulation of mitochondrial dynamics, autophagy, and biogenesis, thereby enhancing mitochondrial function and effectively mitigating H₂S-induced biotoxicity. Our research not only elucidates the biotoxicity mechanisms of H₂S exposure but also provides valuable insights into potential therapeutic strategies that alleviate or eliminate its toxic effects.