Arsenite-induced liver apoptosis via oxidative stress and the MAPK signaling pathway in marine medaka.

Arsenic (As) is widely recognized for its hazards to aquatic organisms; however, its toxicological impacts on apoptosis in marine fish remain inadequately explored. This study investigated the effects of in vivo dietary exposure to 50 or 500 mg/kg AsIII (as NaAsO) over 28 days in marine medaka, alongside in vitro exposure to 50-750 μg/L AsIII for 48 h in a hepatic cell line derived from marine medaka, to elucidate the toxicity and underlying molecular mechanisms. In vivo, As significantly accumulated in liver tissue (1.79-fold compared to the control), causing hepatic lesions and increased apoptosis (4.85 ± 0.56 % and 9.29 ± 1.82 %, respectively). Gene expression analysis showed downregulation of bcl2l1 and upregulation of bax, caspase-3 and caspase-9, indicating mitochondrial pathway-mediated apoptosis. In vitro, As exposure induced hepatocyte morphological changes, reactive oxygen species (ROS) production, and apoptosis. Additionally, mapk1 and mapk3 (ERK pathway) were downregulated both in vivo and in vitro, while mapk14a (P38 pathway), mapk8b and mapk9 (JNK pathway) were upregulated exclusively in hepatocytes. Furthermore, n-acetyl cysteine (NAC) attenuated As-induced apoptosis and modulated the expression of MAPK signaling pathway genes, including mapk3 and mapk8b, suggesting that As-induced oxidative stress regulates apoptosis via the MAPK signaling pathway. In contrast, phenylbutyric acid (PBA) was ineffective in preventing apoptosis. Overall, these results demonstrate that As induces endogenous apoptosis through oxidative stress and the MAPK signaling pathway in marine medaka.