title: Cytotoxic and apoptotic effects on hepatocytes of secondary metabolites obtained from lichens.
abstract: There are a large number of species of Antarctic lichens, and several studies describing the secondary metabolites present in these lichens, as well as the advances in understanding the chemistry of these metabolites, have been reported. In addition, some derivatives displaying interesting antibacterial effects have been described. The cytotoxic and apoptotic effects of 15 secondary metabolites (depsides, depsidones and usnic acid) obtained from Continental (Chilean) and Antarctic lichens were evaluated in primary cultures of rat hepatocytes. Intracellular lactate dehydrogenase release, caspase 3 activation and DNA fragmentation were measured. In this study, we have evaluated a set of markers associated with pivotal steps in the execution phase of apoptosis, in order to detect compounds with apoptotic effects on hepatocytes before significant necrosis takes place. Flow cytometric analysis of DNA fragmentation revealed an increase in apoptotic nuclei with sub-diploid DNA content after the exposure of hepatocytes to sub-cytotoxic concentrations of the compounds. Among these, salazinic acid, stictic acid and psoromic acid displayed significant apoptotic activities.
authors.affiliation: Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 915, 5700 San Luis, Argentina.
authors.forename: Estela Raquel
authors.initials: ER
authors.lastname: Correché
authors.forename: Ricardo Daniel
authors.initials: RD
authors.lastname: Enriz
authors.forename: Marisa
authors.initials: M
authors.lastname: Piovano
authors.forename: Juan
authors.initials: J
authors.lastname: Garbarino
authors.forename: María José
authors.initials: MJ
authors.lastname: Gómez-Lechón
mesh_terms: D000818:Animals; D000864:Antarctic Regions; D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000633:toxicity; D001572:Benzofurans / Q000633:toxicity; D002264:Carboxylic Acids / Q000633:toxicity*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D053630:Depsides; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D062385:Hydroxybenzoates / Q000633:toxicity*; D007783:Lactones / Q000633:toxicity*; D008011:Lichens / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001565:Benzoates; D001572:Benzofurans; D002264:Carboxylic Acids; D053630:Depsides; D062385:Hydroxybenzoates; D007783:Lactones; C073339:usnic acid; C000875:depsidone; C120727:gyrophoric acid; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases