engleski

Gamma-melanocortin hepatoprotection is modulated by antisense peptide of central melanotropic pharmacophore

Introduction: Applications of the antisense peptides in biomedicine are often related to the modulation of peptide and hormone biological function, selective immunomodulation, receptor and vaccine research. The aim of this work was twofold: 1) to investigate the hepatoprotective effects of γ-MSH in experimental hepatitis, and 2) to investigate the modulation γ-MSH function using an antisense peptide of the central melanotropic pharmacophore. Materials and Methods: Antisense peptide sequence Val-Lys-Ala-Thr, of the MSH pharmacophore motif His-Phe-Arg-Trp, was obtained by the complementary mRNA sequence transcription in 3’→5’ direction. Tryptophan spectrofluorometric titrations indicated that antisense peptides bind MSH pharmacophore region. In vivo tests were performed using the experimental model of acetaminophen induced liver lesions in male CBA mice. Acetaminophen was applied intragastrically in a dose of 150 mg/kg, and tested substances were applied intraperitoneally 1 hour before acetaminophen. Mice were sacrificed after 24 hours and intensity of liver injury was estimated by the measurement of plasma transaminase activity and histopathological grading of lesions. Results: It was found that γ-MSH decreases the intensity of liver lesions by the criteria of plasma transaminase activity and histopathological grading of lesions. The hepatoprotective effect of the hormone was dose-dependent. Equimolar dose of antisense peptide Val-Lys-Ala-Thr abolished the protective effects of γ-MSH. When it was administered alone antisense peptide was not effective. Conclusions: 1.Our results justify future pharmacological investigations of γ-MSH in hepatology. 2. Antisense peptide to central pharmacophore for the melanocortin 1, 3, 4 and 5 receptors abolished the hepatoprotective effects of γ-MSH in vivo.

gamma-melanocortin ; hepatoprotection ; antisense ; peptide ; pharmacophore

nije evidentirano