Abstract
This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecific α 2 receptor blocker) + high dose Dex (group B1), ARC239 (a specific α 2B/c receptor blocker) + high dose Dex (group B2), and BRL-44408 (a specific α 2A receptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (all P < 0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 through α 2A receptor, increases the antioxidant levels, and attenuates renal injury during OALT.
Highlights
Orthotopic liver transplantation (OLT) has been considered the best choice for end-stage liver diseases [1]
Compared with group M, the pathological changes and scores of rats pretreated with Dex, groups D1 (122.38 ± 8.99 versus 7.88 ± 6.53, P < 0.01) and D2 (122.38 ± 8.99 versus 56.75 ± 9.71, P < 0.01), were significantly lower, especially in group D2 which received 50 μg/kg Dex
Compared to group D2, the protective effect was reversed in group B1 (56.75 ± 9.71 versus 125 ± 11.19, P < 0.01) which received atipamezole and in group B3 (56.75 ± 9.71 versus 124.13 ± 11.36, P < 0.01) which received BRL-44408
Summary
Orthotopic liver transplantation (OLT) has been considered the best choice for end-stage liver diseases [1]. Acute kidney injury (AKI) is the most common and severe complication after OLT with a 12%–70% [2, 3] incidence rate and an annual mortality rate of up to 35%–45% [4] It is an important factor in early postoperative death and influences the prognosis and rehabilitation of patients [5, 6]. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcriptional factor in cells, which acts against oxidative and stress injury It can enhance the antioxidant enzymes and phase II detoxification enzyme levels in combination with the antioxidant response element (ARE) and plays a key role in the endogenous antioxidative activity [7, 8]. Some researchers have reported that Nrf can provide protective effect by upregulating the expression of heme oxygenase 1 (HO-1), nicotinamide-adenine dinucleotide phosphate
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