The influence of alpha-melanocortin enantiomers on acetaminophen-induced hepatis in mice

L-alpha-Melanocortin is a strong inhibitor of inflammation. It is a promising new anti-inflammatory and hepatoprotective peptide. Consequently, its melanocortin receptors (MC₁, MC₃, MC₄ and MC₅) could be possible targets for the development of new antiinflammatory drugs for chronic inflammatory liver disease. For a long time it has been believed that only the L-enantiomers of amino acids are present in higher animals, but recent investigations show that D-amino acids also exhibit physiological effects in vivo, despite their very small quantities. The aim of this study was to compare hepatoprotective effects of L-alpha-melanocortin and D-alpha-melanocortin using the acetaminophen model of chemical liver damage in male CBA mice.

Tested substances were applied intraperitoneally 60 minutes prior to the intragastric application of acetaminophen (150 mg/kg). Animals were sacrificed 24 hours after the administration of acetaminophen. The criteria for monitoring hepatoprotective effects of the tested substances were biochemical parameters (AST and ALT) and histopathological analysis.

The results obtained by the histopathological analysis and biochemical findings show potent hepatoprotective and anti-inflammatory effects of L-alpha-melanocortin in the liver, and suggest the possibility of modulating liver inflammation by means of melanocortin molecules and related receptors. D-alpha-melanocortin did not show any hepatoprotective effects in vivo.

Our results show that peptide enantiomerism influences the protective effects of alpha-melanocortin peptides in vivo. This concept may be used to modulate peptide function in vivo and antibody binding assay in vitro.