The Influence of α-, β-, and γ-Melanocyte Stimulating Hormone on Acetaminophen Induced Liver Lesions in Male CBA Mice

Abstract

Research over the past decade has indicated that melanocortin peptides are potent inhibitors of inflammation and a promising source of new anti-inflammatory and cytoprotective therapies. The purpose of the present paper is to compare protective effects of α-, β-, and γ-melanocyte stimulating hormone on 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 measurement of plasma transaminase activity (AST and ALT) and histopathological grading of lesions. It was found that α-, β-, and γ-MSH decrease intensity of lesions by both criteria in a dose-dependent manner.

Interaction of α-Melanocortin and Its Pentapeptide Antisense LVKAT: Effects on Hepatoprotection in Male CBA Mice

“…Fluorescence titration was performed with D-α-MSH enantiomer also, but it did not give satisfactory results in terms of the obtained data suggesting very weak (if any) binding under the same experimental conditions. The result of the fluorescence titration of D-α-MSH with LVKAT antisense peptide is consistent with the findings of Turčić et al [ 15 , 16 ] showing that D-α-MSH does not bind antibody to L-α-MSH.…”

“…We tested peptides on the experimental model of acetaminophen (APAP)-induced liver lesions in male CBA mice, a useful animal model of hepatitis often used for the screening of hepatoprotective drugs [ 32 , 33 , 34 ]. Turčić et al [ 15 , 16 ] recently showed that α-MSH, a well known melanocortin peptide with anti-inflammatory and cytoprotective properties, exhibits strong and dose dependent hepatoprotective effects in this model.…”

“…The effects of α-MSH and its antisense peptide LVKAT on the APAP induced liver lesions (scores on scale 0-5 [ 15 , 16 , 32 ]) are presented in Figure 4 , Figure 5 and Figure 6 . Significantly less liver lesions were observed in α-MSH treated animals (2 ± 0.75, mean ± SD), compared to the untreated controls (4.8 ± 0.46, mean ± SD, p < 0.05, Figure 4 ).…”

“…It is currently the most widely studied melanocortin peptide in the context of tissue inflammation and cytoprotection [ 12 , 13 , 14 ]. Recently, Turčić et al [ 15 , 16 ] showed that α-MSH exerts potent hepatoprotective effects in the mouse model of acetaminophen induced hepatotoxicity.…”

Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms

“…9, 13 This system comprises multiple components, including five class A guanine nucleotide–binding protein (G protein)–coupled melanocortin receptors (MCRs) MC1R∼MC5R; endogenous antagonists; and peptide agonists derived from the anterior pituitary gland, including α-melanocyte-stimulating hormone (MSH), β-MSH, γ-MSH, and ACTH. 9, 13 Accumulating data demonstrate that melanocortins, 14 in particular α-MSH 15 and its synthetic mimetics, 16 possess a potent protective activity in acute injuries in multiple organ systems, 17, 18, 19 including the kidney. 15 Nevertheless, although α-MSH has similar MCR agonizing potency as its parent molecule ACTH, 9, 13 the effect of ACTH on AKI has been barely investigated.…”