Dexmedetomidine reduces enteric glial cell injury induced by intestinal ischaemia‐reperfusion injury through mitochondrial localization of TERT

Abstract

This study was performed to uncover the effects of dexmedetomidine on oxidative stress injury induced by mitochondrial localization of telomerase reverse transcriptase (TERT) in enteric glial cells (EGCs) following intestinal ischaemia‐reperfusion injury (IRI) in rat models. Following establishment of intestinal IRI models by superior mesenteric artery occlusion in Wistar rats, the expression and distribution patterns of TERT were detected. The IRI rats were subsequently treated with low or high doses of dexmedetomidine, followed by detection of ROS, MDA and GSH levels. Calcein cobalt and rhodamine 123 staining were also carried out to detect mitochondrial permeability transition pore (MPTP) and the mitochondrial membrane potential (MMP), respectively. Moreover, oxidative injury of mtDNA was determined, in addition to analyses of EGC viability and apoptosis. Intestinal tissues and mitochondria of EGCs were badly damaged in the intestinal IRI group. In addition, there was a reduction in mitochondrial localization of TERT, oxidative stress, whilst apoptosis of EGCs was increased and proliferation was decreased. On the other hand, administration of dexmedetomidine was associated with promotion of mitochondrial localization of TERT, whilst oxidative stress, MPTP and mtDNA in EGCs, and EGC apoptosis were all inhibited, and the MMP and EGC viability were both increased. A positive correlation was observed between different doses of dexmedetomidine and protective effects. Collectively, our findings highlighted the antioxidative effects of dexmedetomidine on EGCs following intestinal IRI, as dexmedetomidine alleviated mitochondrial damage by enhancing the mitochondrial localization of TERT.

DEXMEDETOMIDINE PREVENTS PDIA3 DECREASE BY ACTIVATING Α2-Adrenergic RECEPTOR TO ALLEVIATE INTESTINAL I/R IN MICE

“…DEX has been reported to be a potential drug for the prevention and treatment of intestinal I/R injury ( 7 , 9 , 16 , 18 , 19 ). Our results elaborated that the protection from DEX in mice with intestinal I/R injury evidenced with an inhibition of inflammation, ER stress-dependent apoptosis, and oxidative stress in the intestinal mucosa.…”

Attenuation of intestinal ischemia-reperfusion-injury by anesthetics: a potentially protective effect of anesthetic management in experimental studies

“…Some new protective mechanisms of DEX in intestinal IRI in animal models have been reported in recent years. DEX can attenuate intestinal I/R injury by decreasing ferroptosis and pyroptosis, enhancing mitophagy, promoting the mitochondrial localization of TERT, and microbiota-related mechanisms ( Liu et al, 2021 ; Zhang et al, 2021 ; Dong et al, 2022 ; Hu et al, 2022 ; Hou et al, 2023 ). These findings provide new experimental evidence supporting the protective effect of DEX against intestinal IRI and a unique insight into the clinical use of DEX, which has positive significance for DEX administration in the perioperative period.…”