Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress, mitochondrial dysfunction and apoptosis in rats

Abstract

Previous studies have identified that dexmedetomidine (DEX) treatment can ameliorate the acute lung injury (ALI) induced by lipopolysaccharide and ischemia-reperfusion. However, the molecular mechanisms by which DEX ameliorates lung injury remain unclear. The present study investigated whether DEX, which has been reported to exert effects on oxidative stress, mitochondrial permeability transition pores and apoptosis in other disease types, can exert protective effects in lipopolysaccharide (LPS)-induced ALI by inhibiting oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis. It was revealed that LPS-challenged rats exhibited significant lung injury, characterized by the deterioration of histopathology, vascular hyperpermeability, wet-to-dry weight ratio and oxygenation index (PaO2/FIO2), which was attenuated by DEX treatment. DEX treatment inhibited LPS-induced mitochondrial dysfunction, as evidenced by alleviating the cellular ATP and mitochondrial membrane potential in vitro. In addition, DEX treatment markedly prevented the LPS-induced mitochondrial-dependent apoptotic pathway in vitro (increases of cell apoptotic rate, cytosolic cytochrome c, and caspase 3 activity) and in vivo (increases of |terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells, cleaved caspase 3, Bax upregulation and Bcl-2 downregulation). Furthermore, DEX treatment markedly attenuated LPS-induced oxidative stress, as evidenced by downregulation of cellular reactive oxygen species in vitro and lipid peroxides in serum. Collectively, the present results demonstrated that DEX ameliorates LPS-induced ALI by reducing oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis.

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

“…Dexmedetomidine (DEX) is a central adrenoceptor α 2‐adrenergic receptor agonist with sedative, analgesic, and anti‐stress reaction effects . DEX affects neurons and exerts protective effects by decreasing catecholamine and glutamate levels and preventing neuronal apoptosis .…”

miR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14

“…DEX is a α2-adrenergic drug used in clinic, which can be used as an anti-oxidative drug before anesthesia, reducing the concentration of cytokines in kidney tissue and can also reduce lung damage caused by LPS, ischemia-reperfusion and ventilation in animal models [16][17][18]. DEX has also been shown to reduce oxidative stress and apoptotic lesions in lung tissue [19].…”

Tocotrienols and Oxidative Stress in Oocytes and Developing Embryos

“…This positive feedback mechanism has been termed as "ROS-induced ROS release" (RIRR). Variety of observations support RIRR as the common mechanism for subsequent ROS generation and amplification [43,48,50].…”

“…Within ROS-induced mitochondria, reduced or absence of cristae junctions (CJ) from the mitochondrial matrix suggests of CJ remodeling [50][51][52]. Remodeling of cristae junction facilitates mitochondrial release of cytochrome c, causing apoptosis cascade.…”

“…Other mPTP inhibitors such as CsA, BGK and Ru360, have been identified to reduce percentage of cristae cells [54,55]. The increased permeability of inner mitochondrial membrane allows for more protons, ions and solutes (up to 1.5 kDa in size) to pass through, consequently affecting the chemio-osmotic function of mitochondria [39,50].…”