Protective effect of dexmedetomidine against organ dysfunction in a two-hit model of hemorrhage/resuscitation and endotoxemia in rats

Abstract

Dexmedetomidine (DEX), a selective agonist of α 2 -adrenergic receptors, has anti-inflammation properties and potential beneficial effects against trauma, shock, or infection. Therefore, this study aimed to investigate whether DEX might protect against multiple-organ dysfunction in a two-hit model of hemorrhage/resuscitation (HS) and subsequent endotoxemia. Eighty Wistar rats were randomized into four groups: NS (normal saline), HS/L (HS plus lipopolysaccharide), HS/L+D (HS/L plus dexmedetomidine), and HS/L+D+Y (HS/L+D plus yohimbine). Six hours after resuscitation, blood gas (PaO 2 ) and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urine nitrogen (BUN), creatinine (Cr), TNF-α, IL-β, IL-6, IL-8, IL-10, and nitric oxide (NO) were measured. The histopathology was assayed by staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) were assayed. The PaO 2 levels in HS/L rats were lower whereas the ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, IL-10, and NO levels were higher compared to the control group. The HS/L+D increased PaO 2 and further increased IL-10 and decreased ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, and NO levels of the HS/L groups. In addition, the MDA in the HS/L groups increased whereas SOD activity decreased compared to the control group. Moreover, the HO-1 expression levels were increased by DEX administration in lung, liver, and kidney tissues. Lungs, livers, and kidneys of the HS/L group displayed significant damage, but such damage was attenuated in the HS/L+D group. All of the above-mentioned effects of DEX were partly reversed by yohimbine. DEX reduced multiple organ injury caused by HS/L in rats, which may be mediated, at least in part, by α 2 -adrenergic receptors.

Cepharanthine promotes the effect of dexmedetomidine on the deposition of β-amyloid in the old age of the senile dementia rat model by regulating inflammasome expression

“…Natural antioxidants have shown a beneficial effect on the cellular apoptosis and thus antioxidants are explored as an AD treatment. The literature has suggested that dexmedetomidine has strong antioxidant and anti-inflammatory properties [10]. Data of the present investigation suggest that cepharanthine alone and in combination with dexmedetomidine ameliorates the altered level of oxidative stress and production of ROS and MMP in SD rats.…”

Dexmedetomidine alleviates pulmonary edema through epithelial sodium channel (ENaC) via the PI3K/Akt/Nedd4-2 pathway in LPS- induced acute lung injury

“…Dexmedetomidine (Dex), a highly selective α 2 -adrenegicreceptor (α 2 AR) agonist, can reduce pulmonary edema through inhibiting the production of inflammatory cytokines, including TNF-α, IL-1β and IL-6 in ALI model [13][14][15][16]. Consistent with these studies, our previous studies have found that Dex can attanuate pulmonary edema in LPSinduced ALI, and improve the PaO 2 , reduce the inflammatory response.…”

Dexmedetomidine alleviates blunt chest trauma and hemorrhagic shock‑resuscitation‑induced acute lung injury through inhibiting the NLRP3 inflammasome

“…a number of basic research experiments and clinical trials have reported that dex can protect various organs, including the lungs, by inhibiting oxidative stress, inflammatory responses and apoptosis in a range of diseases (18)(19)(20). The protective effects of dex were recently demonstrated in a two-hit rat model (21). a recent study has shown that dex is relevant to the inhibition of NLRP3 inflammasome activity (19).…”