Effects of α-Melanocortin Enantiomers on Acetaminophen-Induced Hepatotoxicity in CBA Mice.docVIP

Molecules 2009, 14, 5017-5026; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Effects of α-Melanocortin Enantiomers on Acetaminophen- Induced Hepatotoxicity in CBA Mice Petra Tur?i? 1, Mirna Bradamante 2, Karlo Houra 3, Nikola ?tambuk 4,*, Tomislav Kelava 5, Pa?ko Konjevoda 4, Sa?a Kazazi? 4, Dra?en Viki?-Topi? 4 and Biserka Pokri? 4 1 Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Domagojeva 2, 10000 Zagreb, Croatia; E-Mail: pturcic@pharma.hr (P.T.) 2 Department of Dermatology and Venerology, University Hospital Center Zagreb, ?alata 4, 10000 Zagreb, Croatia; E-Mail: mirna.bradamante@kbc-zagreb.hr (M.B.) 3 Department of Neurosurgery, University Hospital “Sestre Milosrdnice”, Vinogradska 29, 10000 Zagreb, Croatia; E-Mail: khoura@kbsm.hr (K.H.) 4 Ru?er Bo?kovi? Institute, Bijeni?ka cesta 54, 10002 Zagreb, Croatia; E-Mails: pkonjev@irb.hr (P.K.); kazazic@irb.hr (S.K.); vikic@irb.hr (D.V-T.); pokric@irb.hr (B.P.) 5 Department of Physiology and Immunology, School of Medicine, University od Zagreb, ?alata 3, 10000 Zagreb, Croatia; E-mail: tkelava@mef.hr (T.K.) * Author to whom correspondence should be addressed; E-Mail: stambuk@irb.hr. Received: 30 September 2009; in revised form: 22 November 2009 / Accepted: 30 November 2009 / Published: 2 December 2009 Abstract: Proteins and peptides in mammals are based exclusively on L-amino acids. Recent investigations show that D-amino acids exhibit physiological effects in vivo, despite of their very small quantities. We have investigated the hepatoprotective effects of the L- and D-enantiomers of α-melanocortin peptide (α-MSH). The results showed that peptide- enantiomerism is related to the protective effects of melanocortin peptides in vivo. L-α- MSH exhibited potent hepatoprotective effect in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice, while its D-mirror