title: Khat (Catha edulis) generates reactive oxygen species and promotes hepatic cell apoptosis via MAPK activation.
abstract: A number of studies have suggested an association between khat (Catha edulis) chewing and acute liver lesions or chronic liver disease. However, little is known about the effects of khat on hepatic cells. In the current study, we investigated the mechanism behind khat-induced apoptosis in the L02 human hepatic cell line. We used cell growth inhibition assay, flow cytometry and Hoechst 33258 staining to measure hepatocyte apoptosis induced by khat. Western blot analysis was used to detect the expression levels of caspase-8 and -9, as well as those of Bax and Bcl-2. We also measured reactive oxygen species production. The results indicated that khat induced significant hepatocyte apoptosis in L02 cells. We found that khat activated caspase-8 and -9, upregulated Bax protein expression and downregulated Bcl-2 expression levels, which resulted in the coordination of apoptotic signals. Khat-induced hepatocyte apoptosis is primarily regulated through the sustained activation of the c-Jun NH2-terminal kinase (JNK) pathway and only partially via the extracellular signal-regulated kinase (ERK) cascade. Furthermore, the khat-induced reactive oxygen species (ROS) production and the activation of the ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the khat-induced activation of JNK and ERK. Our results demonstrate that khat triggers the generation of intracellular ROS and sequentially induces the sustainable activation of JNK, which in turn results in a decrease in cell viability and an increase in cell apoptosis.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors.forename: Morad Dirhem Naji
authors.initials: MD
authors.lastname: Abid
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Xiang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D029754:Catha / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species; D020928:Mitogen-Activated Protein Kinases