title: Hepatoprotective effects of Met-enkephalin on acetaminophen-induced liver lesions in male CBA mice.
abstract: Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for several different animal disease models. In this group plasma alanine aminotransferase and aspartate aminotransferase enzyme activities, as well as liver necrosis score were significantly reduced in comparison to control animals treated with physiological saline (p>0.01). The specificity of the peptide hepatoprotection was investigated from the standpoint of the receptor and peptide blockade. It was concluded that Met-enkephalin effects on the liver were mediated via δ and ζ opioid receptors. Genotoxic testing of Met-enkephalin confirmed the safety of the peptide.
authors.affiliation: Department for Clinical Pathophysiology, Clinical Hospital Centre Split, Šoltanska 1, 21000 Split, Croatia. roko.romast@gmail.com.
authors.forename: Roko
authors.initials: R
authors.lastname: Martinić
authors.affiliation: Department of Urology, University Clinical Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia. hsosic@gmail.com.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Sošić
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Domagojeva 2, 10000 Zagreb, Croatia. pturcic@pharma.hr.
authors.forename: Petra
authors.initials: P
authors.lastname: Turčić
authors.affiliation: Center for Nuclear Magnetic Resonance, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia. pkonjev@irb.hr.
authors.forename: Paško
authors.initials: P
authors.lastname: Konjevoda
authors.affiliation: Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10001 Zagreb, Croatia. afucic@imi.hr.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Fučić
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia. stojkov@irb.hr.
authors.forename: Ranko
authors.initials: R
authors.lastname: Stojković
authors.affiliation: University Hospital Dubrava, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia. garalica@kbd.hr.
authors.forename: Gorana
authors.initials: G
authors.lastname: Aralica
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, 10000 Zagreb, Croatia. mariog@pharma.hr.
authors.forename: Mario
authors.initials: M
authors.lastname: Gabričević
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, 10000 Zagreb, Croatia. tweitner@pharma.hr.
authors.forename: Tin
authors.initials: T
authors.lastname: Weitner
authors.affiliation: Center for Nuclear Magnetic Resonance, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia. stambuk@irb.hr.
authors.forename: Nikola
authors.initials: N
authors.lastname: Stambuk
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D004744:Enkephalin, Methionine / Q000008:administration & dosage*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D020011:Protective Agents / Q000008:administration & dosage
chemical_list: D020011:Protective Agents; D000082:Acetaminophen; D004744:Enkephalin, Methionine
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