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.

Figure 1

(a) Group 1 (Control): showing normal histologic appearance of rat liver tissue without sinusoidal congestion. Hepatocytes took the shape of cell cordons regularly localized around the vena centralis (H-E Bar 50 μm). (b) Group 2: showing normal microscopic findings of liver tissue similar to group 1 (H-E Bar 50 μm). (c) Group 3: dilatation and fibrosis in the vessel wall that located in the portal area of the liver sections. Star: mononuclear cell infiltration in the portal area, black arrow: hemorrhage in the vessel wall of portal area, and yellow arrow: hemorrhage and dilatation in sinusoids (Massone trichrome Bar 100 μm). (d) Group 3: Star indicates dilatation and congestion in sinusoids. Arrow indicates decreased glycogen storage in hepatocytes (PAS Bar 100 μm). (e) Group 3: mononuclear cell infiltration in the portal area and dilatation in vessels together with thickening of the portal and periportal basement membrane (PAS Bar 100 μm). (f) Group 4: slight sinusoidal congestion and thickening of the portal and periportal basement membrane and increased glycogen content following dexmedetomidine treatment (PAS Bar 100 μm).

Figure 2

Representative immunohistochemical staining in liver tissue. (a) Immunohistology assay for hepatic CD68 expression, in group 3 rats the areas of CD68-positive staining were strong in the Kupffer cells that around sinusoids (CD68 immune stain Bar 50 μm). (b) After treatment with dexmedetomidine CD68 positive staining was thin (CD68 immune stain Bar 50 μm). (c) Immunohistochemical staining of liver sections for VEGF shows weak expression in sinusoidal endothelial cells (VEGF immune stain Bar 50 μm). (d) After treatment with dexmedetomidine strong expression of VEGF was observed in the livers of rat (VEGF immune stain Bar 50 μm).

Figure 3

Comparison of liver tissue and serum total oxidant activity levels between groups.

Figure 4

Comparison of VEGF and CD68 values between groups.