Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

Abstract

The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

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

“…The present study observed significant lung injuries and dysfunction following LPS administration, evidenced by deterioration of histopathology, increased vascular permeability, W/D weight ratio of the lung and decreased P a O 2 /FIO 2 , which is consistent with other studies ( 2 , 4 ). In previous studies, the protective effect of DEX against ALI has been demonstrated in several models ( 16 , 17 , 19 ). Following pretreatment of DEX (50 µg/kg), LPS-induced ALI was attenuated, which was reflected by improved histopathological changes, vascular permeability, lung water content and P a O 2 /FIO 2.…”

“…Dexmedetomidine (DEX), a highly selective and potent α2-adrenoreceptor agonist, provides excellent sedation and analgesia with minimal cardiovascular effects. Previous studies have shown that DEX attenuates LPS, ischemia-reperfusion and ventilator-induced lung injury in animal models; however, the mechanism remains unclear ( 16 – 19 ). Additionally, the anti-inflammatory and antiapoptotic effects of DEX have been demonstrated in previous studies ( 20 – 23 ).…”

Dexmedetomidine reduces ventilator-induced lung injury (VILI) by inhibiting Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway

“…As a widely used anesthetic adjuvant in clinical setting, dexmedetomidine has a high affinity for the α 2 -adrenoceptor and is approved for sedation in critically ill patients, due to its sedative effects without respiratory depression [6]. Many studies also showed the anti-inflammatory effect of dexmedetomidine by reducing the levels of inflammatory cytokines in some specific cases [7,23,24]. Based on previous research [9], we set the dose of dexmedetomidine at 1 µg/kg/hour which is the equivalent of the clinical dose in humans.…”

Dexmedetomidine improves acute stress‐induced liver injury in rats by regulating MKP‐1, inhibiting NF‐κB pathway and cell apoptosis

“…DEX has been reported to have diverse pharmacological activities, such as anti‐inflammatory, antiapoptotic, and antioxidative stress effects (Cui et al, ; Sarin & Choudhury, ; Xu, Bao, Si, & Wang, ). Although DEX protects against liver injury caused by acid‐induced acute lung injury (Sen et al, ), there is no information about the potential for DEX involvement in acute stress‐induced liver injury. DEX at a dose of 10–50 μg/kg (ip) had a protective effect against hepatic ischemia–reperfusion injury in rats and did not damage the rat liver (Y. Wang et al, ).…”