Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury

Abstract

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

Keywords: Bcl-2; Wistar rats; acute kidney injury; heme oxygenase-1, Bax; hyperbaric oxygen preconditioning; spontaneously hypertensive rats.

Figure 1

Plasma KIM-1 levels 24 h after reperfusion in normotensive (A) and hypertensive (B) groups. ** p < 0.01 vs. SHAM, # p < 0.05 vs. AKI.

Figure 2

Histopathology of the representative kidney samples collected in different experimental groups (PAS staining, × 20 magnification): W-SHAM (A), W-AKI (B), W-HBO + AKI (C), SHR-SHAM (D), SHR-AKI (E), SHR-HBO + AKI (F).

Figure 3

Bax, Bcl-2 and HO-1 expression in kidney tissue in normotensive (A–C) and hypertensive (D–F) groups. *** p < 0.001, ** p < 0.01, * p < 0.05 vs. SHAM, ## p < 0.01, # p < 0.05 vs. AKI.