Life sciences
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The α2-adrenoceptor inducer dexmedetomidine (Dex) provides renoprotection against ischemia/reperfusion (I/R) injury, but the mechanism of this effect is largely unknown. The present study investigated the effect of Dex on apoptosis induced by hypoxia/reoxygenation (H/R) and the relationship between this effect and gap junction intercellular communication (GJIC). ⋯ Our data suggest that Dex reduced H/R-induced apoptosis through the inhibition of GJ activity by reducing Cx32 protein levels.
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Previous data showed that melatonin maintains liver mitochondrial homeostasis during sepsis, but neither the mechanisms underlying mitochondrial dysfunction nor the target of melatonin are known. ⋯ This work strengthens the use of substrate combinations to identify specific respiratory defects and selective melatonin actions in septic mitochondria. Targeting mitochondrial complex I should be a main therapeutical approach in the treatment of sepsis, whereas the use of melatonin should be considered in the therapy of clinical sepsis.
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Impaired resolution of acute inflammation results in development of chronic inflammatory disorders such as atherosclerosis, asthma and arthritis. Clearance of apoptotic neutrophils by M2 macrophages, the process termed efferocytosis, is critical for complete resolution of inflammation as it prevents secondary necrosis caused by disgorgement of toxic contents from apoptotic cells in the inflamed site. In the present study, we investigated the effect of docosahexaenoic acid (DHA) on efferocytosis. ⋯ These findings indicate that DHA can promote resolution of inflammation by facilitating efferocytosis through M2 macrophage polarization. Therefore, DHA may have a therapeutic potential in the management of inflammatory diseases which are related to impaired resolution of inflammation.
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Endothelins are potent regulators of vascular tone, which also have mitogenic, apoptotic, and immunomodulatory properties (Rubanyi and Polokoff, 1994; Kedzierski and Yanagisawa, 2001; Bagnato et al., 2011). Three isoforms of endothelin have been identified to date, with endothelin-1 (ET-1) being the best studied. ET-1 is classically considered a potent vasoconstrictor. ⋯ High levels of ET-1 are found in alveolar macrophages, leukocytes (Sessa et al., 1991) and fibroblasts (Gu et al., 1991). Clinical and experimental data indicate that ET-1 is involved in the pathogenesis of sepsis (Tschaikowsky et al., 2000; Goto et al., 2012), viral and bacterial pneumonia (Schuetz et al., 2008; Samransamruajkit et al., 2002), Rickettsia conorii infections (Davi et al., 1995), Chagas disease (Petkova et al., 2000, 2001), and severe malaria (Dai et al., 2012; Machado et al., 2006; Wenisch et al., 1996a; Dietmann et al., 2008). In this minireview, we will discuss the role of endothelin in the pathogenesis of infectious processes.
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Endothelin (ET)-1 is the best known potent vasoconstrictor and has been implicated in pathogenesis of sepsis-associated acute kidney injury (AKI) in human or lipopolysaccharide (LPS)-induced AKI in animal models. We have previously shown that ET-1 is highly up-regulated in renal tissues and in plasma after LPS administration. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting beta-blocker, can play an important role in ameliorating levels of LPS-induced up-regulation of renal HIF-1α-ET-1 system and inflammatory cytokines in a rat model of endotoxemia. ⋯ Taken together, these data led us to conclude that landiolol ameliorates the up-regulation of HIF-1α-ET-1 system in minimally morphologically-injured kidney and normalizes biomarkers of renal injury in early hours of endotoxemia of a rat model.