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Molecules 2014, 19(8), 11833-11845; doi:10.3390/molecules190811833

Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

1
Department for Clinical Pathophysiology, Clinical Hospital Centre Split, Šoltanska 1, 21000 Split, Croatia
2
Department of Urology, University Clinical Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia
3
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Domagojeva 2, 10000 Zagreb, Croatia
4
Center for Nuclear Magnetic Resonance, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia
5
Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10001 Zagreb, Croatia
6
Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia
7
University Hospital Dubrava, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia
8
Medical School University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
9
Department of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Received: 23 June 2014 / Revised: 22 July 2014 / Accepted: 31 July 2014 / Published: 7 August 2014
(This article belongs to the Section Medicinal Chemistry)
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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. View Full-Text
Keywords: met-enkephalin; hepatoprotection; genotoxicity; antisense peptide; binding; spectroscopy met-enkephalin; hepatoprotection; genotoxicity; antisense peptide; binding; spectroscopy
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MDPI and ACS Style

Martinić, R.; Šošić, H.; Turčić, P.; Konjevoda, P.; Fučić, A.; Stojković, R.; Aralica, G.; Gabričević, M.; Weitner, T.; Štambuk, N. Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice. Molecules 2014, 19, 11833-11845.

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