title: Glycyrrhizin protection against 3-morpholinosydnonime-induced mitochondrial dysfunction and cell death in lung epithelial cells.
abstract: The present study was designed to assess the preventive effect of licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid against mitochondrial damage and cell death in lung epithelial cells exposed to 3-morpholinosydnonime, a donor of nitric oxide and superoxide. Treatment of lung epithelial cells with 3-morpholinosydnonime resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH. Treatment of glycyrrhizin and 18beta-glycyrrhetinic acid attenuated the 3-morpholinosydnonime-induced mitochondrial damage, formation of reactive oxygen species and GSH depletion and revealed a maximal inhibitory effect at 10 and 1 muM, respectively; beyond these concentrations the inhibitory effect declined. Melatonin, carboxy-PTIO, rutin and uric acid reduced the 3-morpholinosydnonime-induced cell death. The results show that glycyrrhizin and 18beta-glycyrrhetinic acid seem to prevent the toxic effect of 3-morpholinosydnonime against lung epithelial cells by suppressing the mitochondrial permeability transition that leads to the release of cytochrome c and activation of caspase-3. The preventive effect may be ascribed to the inhibitory action on the formation of reactive oxygen species and depletion of GSH. The findings suggest that licorice compounds seem to prevent the nitrogen species-mediated lung cell damage.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.kr
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Han
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D019610:Cytoprotection; D004847:Epithelial Cells / Q000187:drug effects*; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D020030:Nitric Oxide Donors / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects
chemical_list: D020030:Nitric Oxide Donors; C002385:linsidomine; D019695:Glycyrrhizic Acid; D008981:Molsidomine