Zheng Pingping, Zhou Boran, Zheng Yifan, Ke Yangquan, Zhang Weiyin, Xing Mingwei, Zhao Hongjing
College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Heilongjiang, PR China.
Biol Trace Elem Res. 2025 Apr 5. doi: 10.1007/s12011-025-04603-3.
Arsenic (As), a prevalent heavy metal, poses significant risks to the immune systems of living organisms. The spleen is considered one of the major immune organs of As-poisoned aquatic organisms. Zinc (Zn), known for its antioxidant and detoxification properties, may alleviate As-induced immune organ damage, but the underlying mechanism remains unclear. The P38 MAPK/Nrf2/HO- 1 signaling pathway is a crucial endogenous antioxidant pathway that protects organs and acts against cellular oxidative damage. This experiment was designed to investigate the splenic toxicity induced by As in carp and to evaluate the hypothesis that Zn alleviates oxidative stress and inflammatory injury induced by As via the P38 MAPK/Nrf2/HO- 1 signaling pathway. In the experiment, the spleen of the arsenic-exposed group exhibited significant endoplasmic reticulum dilation, formation of apoptotic bodies, and perinuclear cisternae, preliminarily confirming that As can cause severe tissue damage in the spleen of carp. Additionally, the transcriptional activity and protein synthesis of genes related to inflammatory response, oxidative stress, and apoptosis were significantly dysregulated. Notably, Zn supplementation significantly mitigated As-induced damage by enhancing antioxidant enzymes (CAT, SOD, GSH) and suppressing key mediators of stress and apoptosis (Nrf2, NF-κB, PERK, HSP60, and caspases). Additionally, Zn supplementation has been shown to mitigate As-induced spleen injury and associated pathological alterations, including inflammation and necrosis. These findings reveal, for the first time, that Zn alleviates As-induced spleen injury through the P38 MAPK/Nrf2/HO- 1 pathway, providing new insights into the detoxification mechanism of Zn and its potential application in mitigating heavy metal toxicity in aquaculture.
砷（As）是一种普遍存在的重金属，对生物体的免疫系统构成重大风险。脾脏被认为是砷中毒水生生物的主要免疫器官之一。锌（Zn）以其抗氧化和解毒特性而闻名，可能减轻砷诱导的免疫器官损伤，但其潜在机制仍不清楚。P38丝裂原活化蛋白激酶/核因子E2相关因子2/血红素氧合酶-1（P38 MAPK/Nrf2/HO-1）信号通路是一条关键的内源性抗氧化途径，可保护器官并抵抗细胞氧化损伤。本实验旨在研究砷对鲤鱼脾脏的毒性，并评估锌通过P38 MAPK/Nrf2/HO-1信号通路减轻砷诱导的氧化应激和炎症损伤这一假说。在实验中，砷暴露组的脾脏表现出明显的内质网扩张、凋亡小体形成和核周池，初步证实砷可导致鲤鱼脾脏严重的组织损伤。此外，与炎症反应、氧化应激和凋亡相关的基因的转录活性和蛋白质合成明显失调。值得注意的是，补充锌通过增强抗氧化酶（过氧化氢酶、超氧化物歧化酶、谷胱甘肽）和抑制应激及凋亡的关键介质（Nrf2、核因子κB、蛋白激酶R样内质网激酶、热休克蛋白60和半胱天冬酶）显著减轻了砷诱导的损伤。此外，已证明补充锌可减轻砷诱导的脾脏损伤及相关病理改变，包括炎症和坏死。这些发现首次揭示，锌通过P38 MAPK/Nrf2/HO-1途径减轻砷诱导的脾脏损伤，为锌的解毒机制及其在减轻水产养殖中重金属毒性方面的潜在应用提供了新的见解。
