Involvement of caspase in patulin-induced hepatotoxicity in vitro and in vivo

• Published in: Toxicon (Oxford) 2022-01, Vol.206, p.64-73
• Main Authors: Zhang, Baigang, Huang, Chenghui, Lu, Qikun, Liang, Hairong, Li, Jinliang, Xu, Dongmei
• Format: Article
• Language: English
• Subjects: Animals; Animals, Outbred Strains; Caspase; Caspase 3; Caspases; Chemical and Drug Induced Liver Injury; Hepatotoxicity; Lipid Peroxidation; Mice; Patulin; Patulin - toxicity; Vitro; Vivo
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2021.12.017

Patulin (PAT) a kind of mycotoxin, is a widely disseminated mycotoxin found in agricultural products and could cause liver damage. However, evidence on the underlying mechanisms of patulin is still lacking. In the present study, Human liver cancer cells (HepG2) together with a mouse model were used to explore the possible effect and mechanism. The results demonstrated that PAT treatment inhibited cell proliferation and caused liver toxicity in mice. In vitro, PAT inhibited the growth of HepG2 cells in a dose-dependent manner and a time-dependent manner; lipid peroxidation, malondialdehyde (MDA) production increased and the level of SOD and GSH in cells changed significantly. In vivo, Kunming mice were treated with PAT(2.5–15 μM), We indicated that liver damage are observed. The activity of serum alanine transaminase (ALT) and aspartate transaminase (AST) were increased significantly, the hepatocyte nucleus stained with Hematoxylin and Eosin (HE) was blurred and deformed. we also explored the lipid peroxidation and enzymes related to redox and found that the activities of SOD in animals do not change significantly, not like that in cells, while GSHpx played a major role. In addition, we measured the caspase activity of cells and the expression of caspase in mice. PAT-induced the caspase cascade was confirmed with the elevation of the activity and expression of caspase. These data suggest that PAT treatment altered both the redox systems in cells and animals. involvement of caspase in patulin-induced hepatotoxicity. •Patulin inhibits cell proliferation in a dose-dependent manner and in a time-dependent manner.•Patulin altered redox indexes of human liver carcinoma cells and Kunming mice.•Patulin causes hepatotoxicity involving the caspase cascade.•Patulin exerts toxic effects at more than 2.5 μM which means the existing standards should be carried out.