title: Effects of pharmaceutical formulations containing thyme on carbon tetrachloride-induced liver injury in rats.
abstract: BACKGROUND
  Herbal supplements are widely used in the treatment of various liver disases, but some of them may also induce liver injuries. Regarding the infuence of thyme and its constituents on the liver, conflicting results have been reported in the literature. The objective of this study was to examine the influence of two commonly used pharmaceutical formulations containing thyme (Thymus vulgaris L.), tincture and syrup, on carbon tetrachloride-induced acute liver injury in rats.
  
  
  METHODS
  Chemical composition of investigated formulations of thyme was determined by gas chromatography and mass spectrometry. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Liver morphology was characterized by light microscopy using routine hematoxylin and eosin staining.
  
  
  RESULTS
  Thymol was found to be predominant active constituent in both tincture and syrup. Investigated thyme preparations exerted antioxidant effects in liver by preventing carbon tetrachloride-induced increase of lipid peroxidation. Furthermore, co-treatment with thyme preparations reversed the activities of oxidative stress-related enzymes xanthine oxidase, catalase, peroxidase, glutathione peroxidase and glutathione reductase, towards normal values in the liver. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of AST and ALT activities, and histopathologic alterations. Co-administration of thyme tincture resulted in unexpected exacerbation of AST and ALT values in serum, while thyme syrup managed to reduce activites of aminotransferases, in comparison to carbon tetrachloride-treated animals.
  
  
  CONCLUSIONS
  Despite demonstrated antioxidant activity, mediated through both direct free radical scavenging and activation of antioxidant defense mechanisms, thyme preparations could not ameliorate liver injury in rats. Molecular mechanisms of diverse effects of thyme preparations on chemical-induced hepatotoxicity should be more in-depth investigated.
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia. araskovic@hotmail.com.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Rašković
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia. nebojsa.pavlovic@gmail.com.
authors.forename: Nebojša
authors.initials: N
authors.lastname: Pavlović
authors.affiliation: Pharmacy "Novi Sad", Rumenačka 1, Novi Sad, 21000, Serbia. mais1305@gmail.com.
authors.forename: Maja
authors.initials: M
authors.lastname: Kvrgić
authors.affiliation: Institute of Occupational Health, Futoška 121, Novi Sad, 21000, Serbia. sudyjan@gmail.com.
authors.forename: Jan
authors.initials: J
authors.lastname: Sudji
authors.affiliation: Institute of Laboratory Diagnostics, Clinical Center of Vojvodina, Hajduk Veljkova 1, Novi Sad, 21000, Serbia. miticgns@yahoo.com.
authors.forename: Gorana
authors.initials: G
authors.lastname: Mitić
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia. capo.ivan@gmail.com.
authors.forename: Ivan
authors.initials: I
authors.lastname: Čapo
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia. momir.mikov@otago.ac.nz.
authors.forename: Momir
authors.initials: M
authors.lastname: Mikov
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D046930:Thymus Plant / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D002251:Carbon Tetrachloride; D005979:Glutathione Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase