Dexmedetomidine Protects against Ischemia and Reperfusion-Induced Kidney Injury in Rats

Abstract

Acute kidney injury (AKI), a clinical syndrome, is a sudden onset of kidney failure that severely affects the kidney tubules. One potential treatment is dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist that is used as an anesthetic adjuvant. It also has anti-inflammatory, neuroprotective, and sympatholytic qualities. The aim of this study was to establish whether DEX also offers protection against ischemia and reperfusion- (I/R-) induced AKI in rats. An intraperitoneal injection of DEX (25 μg/kg) was administered 30 min prior to the induction of I/R. The results indicate that in the I/R rats, DEX played a protective role by reducing the damage to the tubules and maintaining renal function. Furthermore, in response to I/R, the DEX treatment reduced the mRNA expression of TNF-α, IL-1β, IL-6, and MCP-1 in the kidney tissues and the serum levels of TNF-α, IL-1β, IL-6, and MCP-1. DEX also reduced the levels of oxidative stress and apoptosis in the tubular cells. These results indicate that in response to I/R kidney injury, DEX plays a protective role by inhibiting inflammation and tubular cell apoptosis, reducing the production of reactive oxygen species, and promoting renal function.

Knockdown of lncRNA MALAT1 ameliorates acute kidney injury by mediating the miR‐204/APOL1 pathway

“…A body of evidence suggested that the pathogenesis of sepsis‐induced AKI was thought to be caused by a pro‐inflammatory response 61,62 . Levels of cytokines such as IL‐1β, IL‐6, and TNF‐α have been shown to correlate with the severity and mortality of septic AKI 63,64 . The present study showed that the secretion of pro‐inflammatory cytokines IL‐1β, IL‐6, and TNF‐α was significantly increased in HK‐2 cells after hypoxic treatment.…”

“…61 , 62 Levels of cytokines such as IL‐1β, IL‐6, and TNF‐α have been shown to correlate with the severity and mortality of septic AKI. 63 , 64 The present study showed that the secretion of pro‐inflammatory cytokines IL‐1β, IL‐6, and TNF‐α was significantly increased in HK‐2 cells after hypoxic treatment. More importantly, lncRNA MALAT1 silencing reduced the levels of IL‐1β, IL‐6, and TNF‐α in HK‐2 cells after hypoxia treatment, while miR‐204 inhibitor had a pro‐inflammatory effect on inflammation.…”

Emodin Protects Sepsis Associated Damage to the Intestinal Mucosal Barrier Through the VDR/ Nrf2 /HO-1 Pathway

“…The pharmacological effects of dexamethasone are concentrated in anti-inflammatory (Yu et al, 2019), anti-endotoxin (Yang et al, 2019), immunosuppressive (Hoppstädter et al, 2019;Kim et al, 2020), andanti-shock (O'Connor et al, 2003). Although some studies have shown that dexamethasone is effective in improving inflammation and regulating immune function (Bao and Dai, 2020;Fang et al, 2021), long-term use of glucocorticoids is associated with a series of side effects, including obesity, hypertension, osteoporosis, etc., (Son et al, 2017;Herrera et al, 2020;Xu et al, 2020) Therefore, it is important to find effective drugs with minimal side effects for the treatment of sepsis associated intestinal mucosal injury.…”

Organ-Protective Effects and the Underlying Mechanism of Dexmedetomidine

“…In models of acute lung injury caused by renal ischemia-reperfusion injury, DEX pre-and posttreatment significantly reduce pulmonary edema and inflammatory response by reducing myeloperoxidase (MPO) activity as well as downregulating intercellular adhesion molecule-1 (ICAM-1) and TNF-α mRNA expression [71,72]. In the rat sepsis model [24], DEX inhibits inflammatory response in the lung by the TLR4/myeloid differentiation factor 88/NF-κB pathway and reduces mortality by activating PI3K/Akt/mTOR pathways.…”