Oxytocin ameliorates the immediate myocardial injury in heart transplant through down regulation of the neutrophil dependent myocardial apoptosis

Abstract

Cardiac oxytocin (OT) is structurally identical to that found in the hypothalamus, which thereby indicates that cardiac OT is derived from the same gene and is an active form of OT. The abundance of OT and OT receptors in atrial myocytes shows that, directly and/or via the release of the cardiac hormone atrial natriuretic peptide, OT can regulate the force of cardiac contractions. Previous studies have demonstrated the role of OT in the myocardial inflammatory response. The mechanism by which OT elicits protective myocardial effects in the immediate post-transplantation period is not yet clear, and the role of the early phase inflammatory elements in this mechanism has not yet been studied. As a result, in this study, we have investigated the anti-inflammatory effects of OT on myocardial protection in the immediate post-transplantation period.Methods:Adult male Albino rats were grouped into: Sham, Control, and OT-treated groups. The control and treated groups sustained cervical heterotopic heart transplant. Myocardial injury was assessed by measuring: Plasma cardiac troponin I, myocardial proinflammatory cytokines, and histopathological assessment for score of injury, and degree of apoptosis. Myocardial myeloperoxidase, neutrophil infiltration, and neutrophil chemotactant agents, reactive oxygen species, and reactive nitrogen species formation all were measured in the myocardium after 3 hour of reperfusion to assess the neutrophil-dependant myocardial injury and the mechanism involved.Results:Oxytocin down-regulates the neutrophil chemotactant agents the KC/CXCL1 and MIP-2/CXCL2 which recruit less neutrophil into myocardium, this decrement in myocardial PMN infiltration is associated with less reactive oxygen species and reactive nitrogen species formation in the myocardium after 3 hours of global ischemia reperfusion. These oxytocin-induced down-regulation inflammatory and oxidative processes will end in less myocardial injury through impedance in the post-myocardial ischemia/reperfusion apoptotic process.Conclusion:Oxytocin ameliorates myocardial injury in heart transplant through down-regulation the myocardial inflammatory response, reactive oxygen species, and neutrophil-dependant myocardial apoptosis.

Angiogenic Potential of Bone Marrow Derived CD133+ and CD271+ Intramyocardial Stem Cell Trans- Plantation Post MI

“…However, the same applies to the expression of IL1B and IL6 as well as Timp1 [37] ( Figure 4B). Al-Amran and co-workers demonstrated that down-regulation of Cxcl2 results in decrement in myocardial neutrophil infiltration, which is associated with less reactive oxygen species and reactive nitrogen species formation after global ischemia reperfusion apoptosis [38]. Therefore, we assume, that CD133 + cell therapy may have a valuable impact on a moderate course of the neutrophil-mediated tissue injury [39], although, we only could observe a significant lower TGFβ3 mRNA level of this fibrotic marker in MI133 therapy group when compared with MI271 [40].…”

Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice

“…Furthermore, co-administration of an OT receptor antagonist blocks the protective effects of OT during cardiac ischemia [ 10 ] or cerebral ischemia in rats [ 9 ]. The protective actions of OT in these models may be associated with decreased levels of circulating pro-inflammatory cytokines [ 12 , 13 ] and decreased neutrophil infiltration to the site of injury [ 14 , 15 ]. Moreover, OT inhibits LPS-stimulated pro-inflammatory cytokine secretion from macrophages and endothelial cells [ 16 ].…”

Treatment with oestrogen‐receptor agonists or oxytocin in conjunction with exercise protects against myocardial infarction in ovariectomized rats

“…In agreement with the aforementioned studies, the results of the present study showed that OT treatment in OVX rats potently improved the EF before the induction of infarct, and the levels of pro-inflammatory cytokines measured after the I/R insult were suppressed in OT-treated OVX rats, suggesting that OT may exert an alternative effect by maintaining anti-inflammatory-pro-inflammatory cytokine balance within the injured heart. Recently, cardioprotective effects of OT in the myocardium of rats after I/R were suggested to involve the downregulation of the myocardial inflammatory response, reactive oxygen species and neutrophil-dependent myocardial apoptosis (Al-Amran & Shahkolahi, 2014), as well as the modulation of mitochondrial ATP-dependent potassium channels and permeability transition pores . In a rabbit model of myocardial I/R, post-infarct treatment with OT exerted antifibrotic and angiogenic effects, suggesting the long-term beneficial effects of OT on cardiac function and remodelling (Kobayashi et al 2009).…”

“…In contrast, the cardioprotective effects of regular exercise, verified by several epidemiological studies (Shephard & Balady, 1999;Lavie et al 2009), appear to involve the upregulation of the cardiac OT and ANP systems (Gutkowska et al 2007) and increased hypothalamic OT content and gene expression (Braga et al 2000;Martins et al 2005). Furthermore, in several inflammatory models, including myocardial injury in heart transplant, OT was shown to exert protective effects through the downregulation of inflammatory and oxidative processes (Tugtepe et al 2007;Ç etinel et al 2010;Al-Amran & Shahkolahi, 2014). No data are present regarding the anti-inflammatory effects of OT on menopause-associated myocardial injury.…”

“…; Çetinel et al . ; Al‐Amran & Shahkolahi, ). No data are present regarding the anti‐inflammatory effects of OT on menopause‐associated myocardial injury.…”