Podophyllotoxin mediates hepatic toxicity via the C5a/C5aR/ROS/NLRP3 and cGMP/PKG/mTOR axis in rats based on toxicological evidence chain (TEC) concept by phosphoproteomic analysis

• Published in: Ecotoxicology and environmental safety Vol. 289; p. 117441
• Main Authors: Liu, Chuanxin, Huang, Xiaobin, Kong, Jiao, Li, Xuejiao, Wang, Yuming, Zhang, Fangfang, Duan, Jiajia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2025; Elsevier
• Subjects: Animals; C5a/C5aR/ROS/NLRP3 axis; CGMP/PKG/mTOR/NLRP3 axis; Chemical and Drug Induced Liver Injury - metabolism; Hepatotoxicity; Liver - drug effects; Male; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Phosphorylated proteomics; Podophyllotoxin; Podophyllotoxin - toxicity; Proteomics; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Toxicological evidence chain (TEC) concept; Phosphorylated proteomics; CGMP/PKG/mTOR/NLRP3 axis; Toxicological evidence chain (TEC) concept; Podophyllotoxin; C5a/C5aR/ROS/NLRP3 axis; Hepatotoxicity

Podophyllotoxin (PPT), a highly active compound extracted from the rhizome of Dysosma versipellis (DV), has been used as an effective anti-cancer drug clinically since the 1950s. It possesses various biological activities, including antiviral and antitumor effects. However, its clinical application...