Effects of alpha-melanocortin enantiomers on acetaminophen-induced hepatotoxicity in CBA mice.
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 Land D-enantiomers of alpha-melanocortin peptide (alpha-MSH). The results showed that peptide-enantiomerism is related to the protective effects of melanocortin peptides in vivo. L-alpha-MSH exhibited potent hepatoprotective effect in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice, while its D-mirror image was inefficient. Furthermore, the antibody to the L-peptide did not recognize the D-structure. The results indicate that the opposite peptide configuration may be used to modulate its function and metabolism in vivo and in vitro.
Turcić
Petra
P
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Domagojeva 2, 10000 Zagreb, Croatia. pturcic@pharma.hr
Bradamante
Mirna
M
Houra
Karlo
K
Stambuk
Nikola
N
Kelava
Tomislav
T
Konjevoda
Pasko
P
Kazazić
Sasa
S
Vikić-Topić
Drazen
D
Pokrić
Biserka
B
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D002942:Circular Dichroism; D008099:Liver / Q000187:drug effects*; D053486:Melanocortins / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D013237:Stereoisomerism
D053486:Melanocortins; D000082:Acetaminophen