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 α ₂-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.

Figure 1

Dexmedetomidine (DEX) preconditioning showed renoprotective effects histologically (10x). Renal injury was inflicted in the experimental group by removing the left kidney and clamping the right renal artery for 45 min (renal ischemia-reperfusion (I/R)). In the sham control group, both renal pedicles were dissected without occlusion. DEX was administered 30 min prior to ischemia. Representative microphotographs were taken from (a) the sham control group, (b) the I/R group, (c) the DEX (25 μg/kg)+I/R group, and (d) the quantification of the histological scores following I/R in rats. The histological damages were indicated by black arrows. The data are the mean ± SD (n = 6).∗p < 0.05.

Figure 2

Renal function in rats subjected to the sham procedure, untreated ischemia-reperfusion (I/R), or I/R with dexmedetomidine (DEX) treatment. Levels of (a) serum creatinine, (b) serum urea nitrogen, (c) serum neutrophil gelatinase-associated lipocalin (NGAL), and (d) cystatin C (Cys C) in the sham control, I/R, and DEX (25 μg/kg)+I/R groups. The data are the mean ± SD (n = 6). ∗p < 0.05.

Figure 3

Extent of oxidative stress in rats subjected to the sham procedure, untreated ischemia-reperfusion (I/R), or I/R with dexmedetomidine (DEX) treatment. Levels of (a) malondialdehyde (MDA), (b) glutathione (GSH), and (c) superoxide dismutase (SOD) in the sham control, I/R, and DEX (25 μg/kg)+I/R groups. The data are the mean ± SD (n = 6). ∗p < 0.05.

Figure 4

The mRNA levels of the inflammatory mediators in the rat kidneys or the serum levels of the inflammatory mediators subjected to the sham procedure, ischemia-reperfusion (I/R), or I/R with dexmedetomidine (DEX) treatment. Reverse transcription polymerase chain reaction (RT-PCR) tests of the mRNA levels of (a) IL-1β, (b) IL-6, (c) MCP-1, and (d) TNF-α in the kidney tissues from the sham control, I/R, and DEX (25 μg/kg)+I/R groups. Enzyme-linked immunosorbent assay (ELISA) of the levels of (e) IL-1β, (f) IL-6, (g) MCP-1, and (h) TNF-α in the sera from the sham control, I/R, and DEX (25 μg/kg)+I/R groups. The data are the mean ± SD (n = 6). ∗p < 0.05.

Figure 5

Apoptosis was detected in the rat kidneys via terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling (TUNEL) staining (40x) in rats subjected to the sham procedure, untreated ischemia-reperfusion (I/R), or I/R with dexmedetomidine (DEX) treatment. Representative microphotographs were taken from (a) the sham control group, (b) the I/R group, (c) the DEX (25 μg/kg)+I/R group, and (d) the apoptosis rate following I/R in the rats. The data are the mean ± SD (n = 6). ∗p < 0.05.