title: Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL/6 mice.
abstract: Our aim was to investigate the antioxidant potential of lycopene in different experimental liver models: in vitro, to evaluate the influence of lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway. The role of NADPH oxidase was evaluated by measuring its inhibition potential using an inhibitor of this enzyme. In the in vivo study, male C57BL/6 mice received lycopene (10 or 100 mg/kg by oral gavage) and 1 h later, acetaminophen (APAP) (500 mg/kg) was administrated. Lycopene decreased ROS production in SK-Hep-1 cells through inhibition of NADPH oxidase, brought about in the PKC pathway. Lycopene improved hepatotoxicity acting as an antioxidant, reduced GSSG and regulated tGSH and CAT levels, reduced oxidative damage primarily by decreasing protein carbonylation, promoted the downregulation of MMP-2 and reduced areas of necrosis improving the general appearance of the lesion in C57BL/6 mice. Lycopene is a natural compound that was able to inhibit the production of ROS in vitro and mitigate the damage caused by APAP overdose in vivo.
authors.affiliation: Postgraduated Program in Biological Sciences of the Research Center for Biological Sciences - NUPEB, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, 35.400-000, Brazil; Department of Biological Sciences, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Brazil.
authors.forename: Ana Carla Balthar
authors.initials: ACB
authors.lastname: Bandeira
authors.affiliation: Postgraduated Program in Health and Nutrition, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, 35.400-000, Brazil.
authors.forename: Talita Prato
authors.initials: TP
authors.lastname: da Silva
authors.affiliation: Postgraduated Program in Biological Sciences of the Research Center for Biological Sciences - NUPEB, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, 35.400-000, Brazil.
authors.forename: Glaucy Rodrigues
authors.initials: GR
authors.lastname: de Araujo
authors.affiliation: Postgraduated Program in Biological Sciences of the Research Center for Biological Sciences - NUPEB, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, 35.400-000, Brazil.
authors.forename: Carolina Morais
authors.initials: CM
authors.lastname: Araujo
authors.affiliation: Department of Biological Sciences, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Brazil.
authors.forename: Rafaella Cecília
authors.initials: RC
authors.lastname: da Silva
authors.affiliation: Postgraduated Program in Biological Sciences of the Research Center for Biological Sciences - NUPEB, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, 35.400-000, Brazil; Department of Biological Sciences, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Brazil.
authors.forename: Wanderson Geraldo
authors.initials: WG
authors.lastname: Lima
authors.affiliation: Postgraduated Program in Biological Sciences of the Research Center for Biological Sciences - NUPEB, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, 35.400-000, Brazil; Department of Biological Sciences, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Brazil.
authors.forename: Frank Silva
authors.initials: FS
authors.lastname: Bezerra
authors.affiliation: Postgraduated Program in Biological Sciences of the Research Center for Biological Sciences - NUPEB, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, 35.400-000, Brazil; Department of Biological Sciences, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Brazil. Electronic address: dani.caldeiracosta@gmail.com.
authors.forename: Daniela Caldeira
authors.initials: DC
authors.lastname: Costa
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002338:Carotenoids / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015759:Ionomycin / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000077276:Lycopene; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D002338:Carotenoids; D000082:Acetaminophen; D015759:Ionomycin; D002374:Catalase; D005979:Glutathione Peroxidase; D019255:NADPH Oxidases; D005980:Glutathione Reductase; D020778:Matrix Metalloproteinase 2; D005978:Glutathione; D000077276:Lycopene
keywords: Acetaminophen; C57BL/6 mice; Hepatotoxicity; Lycopene; Oxidative stress; SK-Hep-1 cells