title: The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2).
abstract: Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.
authors.affiliation: Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey sezinp@gmail.com.
authors.forename: S S
authors.initials: SS
authors.lastname: Palabiyik
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Karakus
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: Z
authors.initials: Z
authors.lastname: Halici
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Cadirci
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
authors.forename: Y
authors.initials: Y
authors.lastname: Bayir
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Ayaz
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: I
authors.initials: I
authors.lastname: Cinar
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000081007:Cymenes; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D013943:Thymol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D000081007:Cymenes; D016207:Cytokines; D039821:Monoterpenes; D000082:Acetaminophen; D013943:Thymol; C073316:carvacrol
keywords: Acetaminophen toxicity; HepG2-cultured cell; IL-1β; TNF-α; carvacrol; thymol