title: Acetaminophen-induced hepatotoxicity: Preventive effect of trans anethole.
abstract: The hepatotoxicity induced by APAP is caused by the excessive production of N-acetyl-para-benzoquinone imine (NAPQI), which, when reacting with hepatic proteins proved to cause irreversible lesions. Associated with this process, an intense inflammatory process is also evidenced, characterized by the increased cell influx and production/release of inflammatory mediators. Trans anethole, an aromatic compounds has been showed anti-inflammatory efficacy by inhibit the cellular recruitment and synthesis/releases of many proinflammatory mediators such as prostaglandin (PGE2), cytokines (TNF, IL-1) and nitrico oxide (NO). The aim of this study is to investigate the effect of trans anethole on some inflammatory parameters that are involved in hepatotoxicity induced by high doses of acetaminophen. Our results demonstrate that treatment with AN at doses 125 and 250mg/kg once a day for seven days prevented the changes caused by the APAP overdose, showing less intensity in the histological changes (necrosis, size of hepatocyte area and inflammatory infiltration), and corroborating the findings of serum activities of transaminases and phosphatases and the activity of the enzyme myeloperoxidase. In addition, the treatment prevented the up-regulation of proinflammatory mediators such as NO, TNF, IL-1α, MIP-1α and MCP-1 and induced the up-regulation of anti-inflammatory cytokines (IL-4 and IL-10). Thus, our results demonstrate a possible protective effect of trans anethole on the hepatotoxicity induced by APAP.
authors.affiliation: Department of Pharmacology and Therapeutics, Bloco K68, State University of Maringá, Avenue Colombo, 5790, Jd. Universitário, Maringá, PR, 87020-900, Brazil. Electronic address: brunoambrosiorocha@gmail.com.
authors.forename: Bruno Ambrósio
authors.initials: BA
authors.lastname: da Rocha
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Rua Alexandre Fleming, 105, 13084-971, Campinas, SP, Brazil. Electronic address: ale_mileni@hotmail.com.
authors.forename: Alessandra M Versuti
authors.initials: AM
authors.lastname: Ritter
authors.affiliation: Department of Pharmacology and Therapeutics, Bloco K68, State University of Maringá, Avenue Colombo, 5790, Jd. Universitário, Maringá, PR, 87020-900, Brazil. Electronic address: francieleames@gmail.com.
authors.forename: Franciele Queiroz
authors.initials: FQ
authors.lastname: Ames
authors.affiliation: Department of Food Technology, Federal University of Technology, Paraná (UTFPR), Post-Graduation Program of Food Technology (PPGTA), POBox 271, BR 369, km 0.5, 87301-006, Campo Mourão, PR, Brazil. Electronic address: odinei@utfpr.edu.br.
authors.forename: Odinei Hess
authors.initials: OH
authors.lastname: Gonçalves
authors.affiliation: Department of Food Technology, Federal University of Technology, Paraná (UTFPR), Post-Graduation Program of Food Technology (PPGTA), POBox 271, BR 369, km 0.5, 87301-006, Campo Mourão, PR, Brazil. Electronic address: fernanda@utfpr.edu.br.
authors.forename: Fernanda Vitória
authors.initials: FV
authors.lastname: Leimann
authors.affiliation: Department of Biochemistry, Bloco I89, State University of Maringá, Avenue Colombo, 5790, Jd. Universitário, Maringá, PR, 87020-900, Brazil. Electronic address: liviabracht@gmail.com.
authors.forename: Lívia
authors.initials: L
authors.lastname: Bracht
authors.affiliation: Department of Physiological Science, Bloco H79, State University of Maringá, Avenue Colombo, 5790, Jd. Universitário, Maringá, PR, 87020-900, Brazil. Electronic address: mrmnatali@uem.br.
authors.forename: Maria Raquel Marçal
authors.initials: MR
authors.lastname: Natali
authors.affiliation: Department of Pharmacology and Therapeutics, Bloco K68, State University of Maringá, Avenue Colombo, 5790, Jd. Universitário, Maringá, PR, 87020-900, Brazil.
authors.forename: Roberto Kenji Nakamura
authors.initials: RK
authors.lastname: Cuman
authors.affiliation: Department of Pharmacology and Therapeutics, Bloco K68, State University of Maringá, Avenue Colombo, 5790, Jd. Universitário, Maringá, PR, 87020-900, Brazil. Electronic address: cabamado@uem.br.
authors.forename: Ciomar Ap
authors.initials: CA
authors.lastname: Bersani-Amado
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000081248:Allylbenzene Derivatives; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
chemical_list: D000081248:Allylbenzene Derivatives; D018712:Analgesics, Non-Narcotic; D000840:Anisoles; D000082:Acetaminophen; C006578:anethole
keywords: Acetaminophen; Hepatoprotection; Trans anethole