Varespladib mitigates acute liver injury via suppression of excessive mitophagy on Naja atra envenomed mice by inhibiting PLA2

• Published in: Toxicon (Oxford) 2024-05, Vol.242, p.107694-107694, Article 107694
• Main Authors: Zhao, Wenjie, Liu, Jiahao, Wang, Sidan, Tao, Qinqin, Lei, Qiongqiong, Huang, Chunhong
• Format: Article
• Language: English
• Subjects: Acute liver injury; Mitophagy; Naja atra; Snakebite; Varespladib
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2024.107694

Snakebite envenomation often leads to severe visceral injuries, including acute liver injury (ALI). However, the toxicity mechanism remains unclear. Moreover, varespladib can directly inhibit phospholipase A2 (PLA2) in snake venom, but its protective effect on snakebite-induced ALI and the mechanism have not been clarified. Previous studies have shown that snake venom PLA2 leads to neuron cell death via reactive oxygen species (ROS), one of the initial factors related to the mitophagy pathway. The present study group also found that ROS accumulation occurred after Naja atra envenoming. Hematoxylin and eosin (H/E) staining and immunohistochemistry (IHC) were performed to identify the expression of inflammatory factors in the liver tissue, and flow cytometry and immunofluorescence were used to detect ROS levels and mitochondrial function. Immunofluorescence and western blotting were also used for detecting mitophagy pathway-related proteins. The results showed that N. atra bite induced ALI by activating mitophagy and inducing inflammation and that varespladib had a protective effect. Collectively, these results showed the pathological mechanism of ALI caused by N. atra bite and revealed the protective effect of varespladib. [Display omitted] •N.atra venom causes acute liver injury(ALI), which accompanies with ROS generation.•Excess ROS could induce mitophagy.•Varespladib could effectively allevitate ALI caused by N.atra venom.