title: Hypericum perforatum Reduces Paracetamol-Induced Hepatotoxicity and Lethality in Mice by Modulating Inflammation and Oxidative Stress.
abstract: Hypericum perforatum is a medicinal plant with anti-inflammatory and antioxidant properties, which is commercially available for therapeutic use in Brazil. Herein the effect of H. perforatum extract on paracetamol (acetaminophen)-induced hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice were investigated. HPLC analysis demonstrated the presence of rutin, quercetin, hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol (0.15-3.0 g/kg, p.o.) induced dose-dependent mortality. The sub-maximal lethal dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study. H. perforatum (30-300 mg/kg, i.p.) dose-dependently reduced paracetamol-induced lethality. Paracetamol-induced increase in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, and hepatic myeloperoxidase activity, IL-1β, TNF-α, and IFN-γ concentrations as well as decreased reduced glutathione (GSH) concentrations and capacity to reduce 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate radical cation; ABTS˙(+) ) were inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum protects mice against paracetamol-induced lethality and liver damage. This effect seems to be related to the reduction of paracetamol-induced cytokine production, neutrophil recruitment, and oxidative stress.
authors: Department of Pathology, Biological Science Centre, State University of Londrina, Londrina, PR, Brazil.
authors: Miriam S N
authors: MS
authors: Hohmann
authors: Department of Pathology, Biological Science Centre, State University of Londrina, Londrina, PR, Brazil.
authors: Renato D R
authors: RD
authors: Cardoso
authors: Department of Pathology, Biological Science Centre, State University of Londrina, Londrina, PR, Brazil.
authors: Victor
authors: V
authors: Fattori
authors: Department of Pharmaceutical Sciences, Health Sciences Centre, State University of Londrina, Londrina, PR, Brazil.
authors: Nilton S
authors: NS
authors: Arakawa
authors: Núcleo de Pesquisa em Produtos Naturais e Sintéticos, Departamento de Química e Física, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do café, s/n, Campus universitário, Monte Alegre, 14040-903, Ribeirão Preto, SP, Brazil.
authors: José C
authors: JC
authors: Tomaz
authors: Núcleo de Pesquisa em Produtos Naturais e Sintéticos, Departamento de Química e Física, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do café, s/n, Campus universitário, Monte Alegre, 14040-903, Ribeirão Preto, SP, Brazil.
authors: Norberto P
authors: NP
authors: Lopes
authors: Department of Pharmaceutical Sciences, Health Sciences Centre, State University of Londrina, Londrina, PR, Brazil.
authors: Rubia
authors: R
authors: Casagrande
authors: Department of Pathology, Biological Science Centre, State University of Londrina, Londrina, PR, Brazil.
authors: Waldiceu A
authors: WA
authors: Verri
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000873:Anthracenes; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D005978:Glutathione / Q000378:metabolism; D020902:Hypericum / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010569:Perylene / Q000031:analogs & derivatives / Q000032:analysis; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000032:analysis; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D011794:Quercetin / Q000032:analysis; D012431:Rutin / Q000032:analysis; D013729:Terpenes / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000873:Anthracenes; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D010936:Plant Extracts; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha; D000082:Acetaminophen; D012431:Rutin; D010569:Perylene; C004965:hypericin; D011794:Quercetin; D010696:Phloroglucinol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C056602:pseudohypericin; C001654:hyperforin
keywords: Hypericum perforatum; cytokines; oxidative stress; paracetamol hepatotoxicity