Melanocortins as potential therapeutic agents in severe hypoxic conditions

Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest

“…The restored values of venous PO 2 and SO 2 , here shown, indicate that melanocortins are able to improve circulatory functions, and those of PCO 2 , pH, HCO À 3 and SBE reflect a reversal of metabolic acidosis, according to previous studies carried out in other hypoxic conditions such as circulatory shock (for review see: Giuliani et al, 2010Giuliani et al, , 2012. Of interest, lactate levels markedly increase only during CA (Kurita et al, 2010), and normal blood concentration is usually reached within 1 h after return to spontaneous circulation, in agreement with our present results.…”

“…This is in agreement with the idea that epinephrine may exacerbate CA/ CPR-induced heart dysfunction as a consequence of increased myocardial oxygen demand (Lin et al, 2014;Yu et al, 2013). Melanocortins have been shown to induce multi-organ protection in several experimental models of hypoxic conditions, including circulatory shock, respiratory arrest, brain ischemia, myocardial ischemia and more, and many investigations (both past and recent) suggest that these protective effects result from brain melanocortin MC 3 /MC 4 receptor-activated anti-inflammatory mechanisms, mediated by the vagus nerve (Bazzani et al, 2002;Bertolini et al, 1989;Getting et al, 2006;Giuliani et al, 2007aGiuliani et al, , 2007bGiuliani et al, , 2012Guarini et al, 1997a;Mioni et al, 2003Mioni et al, , 2005Ottani et al, 2010Ottani et al, , 2013. Indeed, melanocortins pass the blood-brain barrier in pharmacologically relevant concentration (Catania et al, 2004;Giuliani et al, 2012), and in previous studies with experimental models of short-term and prolonged myocardial ischemia/ reperfusion we demonstrated that melanocortins induce cardioprotection through a brain activation of an efferent vagal fibremediated cholinergic anti-inflammatory pathway (Mioni et al, 2005;Ottani et al, 2010).…”

“…The endogenous peptides melanocortins, namely adrenocorticotropin/melanocyte-stimulating hormone (ACTH/MSH) group , α-MSH, and shorter fragments] (Catania et al, 2004;Corander et al, 2009;Giuliani et al, 2012;Wikberg and Mutulis, 2008), as well as synthetic analogs, exert cardioprotective effects. These neuropeptides have been shown to attenuate free radical discharge, inflammatory and apoptotic responses induced by myocardial ischemia/reperfusion in rats and mice, to stimulate anti-apoptotic reactions, and to reduce reperfusion-induced arrhythmias as well as infarct size (Bazzani et al, 2002;Getting et al, 2006;Mioni et al, 2003Mioni et al, , 2005Ottani et al, 2010).…”

“…These neuropeptides have been shown to attenuate free radical discharge, inflammatory and apoptotic responses induced by myocardial ischemia/reperfusion in rats and mice, to stimulate anti-apoptotic reactions, and to reduce reperfusion-induced arrhythmias as well as infarct size (Bazzani et al, 2002;Getting et al, 2006;Mioni et al, 2003Mioni et al, , 2005Ottani et al, 2010). Further, melanocortins have a resuscitating effect during respiratory arrest and hemorrhagic shock, and afford neuroprotection in conditions of global and focal brain ischemia (Bertolini et al, 1989;Giuliani et al, 2007bGiuliani et al, , 2012Guarini et al, 1997a). Recently we have shown that janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) -signaling pathways that play an established cardioprotective role (Bolli et al, 2011;Minamino, 2012;Obana et al, 2012;Xuan et al, 2001Xuan et al, , 2005 -are involved in the cardioprotective effect of melanocortins against ischemia/reperfusion-induced damage (Ottani et al, 2013).…”

Avaliação do efeito anti-inflamatório do hormônio alfa estimulador de melanócito (Alfa MSH) em modelo experimental de lúpus

“…Pacientes lúpicos têm níveis séricos alterados de IFN-α, IFN-γ, TNF-α, IL-6 e IL-10 que estão correlacionados com a atividade e gravidade da doença (Yap;Lai, 2013) . O hormônio α-MSH via receptores MC1R e MC3R, atua na inibição do NFkB (Giuliani et al, 2012 (Chae et al, 2008;Bhatnagar, 2011;Richards et al, 1998a;Summers et al, 2010) . Além disso, camundongos knockout para IL-6 não desenvolvem autoanticorpos anti-DNA fita dupla , fator reumatóide e lesão renal após a administração de pristane (Richards et al, 1998a) .…”