Hyperbaric oxygen preconditioning and the role of NADPH oxidase inhibition in postischemic acute kidney injury induced in spontaneously hypertensive rats

Abstract

Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI) and hypertension might contribute to the increased incidence of AKI. The purpose of this study was to investigate the effects of single and combined hyperbaric oxygen (HBO) preconditioning and NADPH oxidase inhibition on oxidative stress, kidney function and structure in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. HBO preconditioning was performed by exposing to pure oxygen (2.026 bar) twice a day for two consecutive days for 60 minutes, and 24h before AKI induction. For AKI induction, the right kidney was removed and ischemia was performed by clamping the left renal artery for 45 minutes. NADPH oxidase inhibition was induced by apocynin (40 mg/kg b.m., intravenously) 5 minutes before reperfusion. AKI significantly increased renal vascular resistance and reduced renal blood flow, which were significantly improved after apocynin treatment. Also, HBO preconditioning, with or without apocynin treatment showed improvement on renal hemodynamics. AKI significantly increased plasma creatinine, urea, phosphate levels and lipid peroxidation in plasma. Remarkable improvement, with decrease in creatinine, urea and phosphate levels was observed in all treated groups. HBO preconditioning, solitary or with apocynin treatment decreased lipid peroxidation in plasma caused by AKI induction. Also, combined with apocynin, it increased catalase activity and solitary, glutathione reductase enzyme activity in erythrocytes. While AKI induction significantly increased plasma KIM-1 levels, HBO preconditioning, solitary or with apocynin decreased its levels. Considering renal morphology, significant morphological alterations present after AKI induction were significantly improved in all treated groups with reduced tubular dilatation, tubular necrosis in the cortico-medullary zone and PAS positive cast formation. Our results reveal that NADPH oxidase inhibition and hyperbaric oxygen preconditioning, with or without NADPH oxidase inhibition may have beneficial effects, but their protective role should be evaluated in further studies.

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

“…Previously, we have shown that HBO preconditioning succesfully blunted the harmful effects of IR injury in AKI of Wistar as well as SH rats by improving systemic oxidative stress, antioxidant defense, therefore normalized renal hemodynamic parameters [ 12 , 28 ]. Here we focused on the effects of HBO preconditioning on renal function through the assessment of GFR and its association with the endogenous antioxidant heme oxygenase-1 and markers of apoptosis, in the same experimental model.…”

“…We still do not know all the pathways how HBO therapeutical modality ameliorates the renal function in experimental postischemic AKI, but we can assume that several mechanisms, are involved. In addition to improvement in renal blood flow and oxidative stress parameters [ 12 , 28 ], increased HO-1 expression with its cytoprotective action, as well as increased anti-apoptotic Bcl-2 protein can contribute to HBO preconditioning beneficial effects, in experimental model of AKI.…”

“…Systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) were measured 24 h after reperfusion by direct method, through a femoral artery catheter (PE-50, Clay-Adams Parsippany, NY, USA), connected to a physiological data acquisition system (9800 TCR Cardiomax II-TCR, Columbus, OH, USA), as previously described [ 28 ]. During this procedure, the rats were anaesthetized by injecting 35 mg/kg b.w.…”

Efficacy and safety evaluation of hyperbaric oxygen therapy for patients with ulcerative colitis

“…UC is a refractory and immune-related intestinal lesion with repeated attack and unknown etiology, which substantially diminishes the quality of life of patients. [ 17 ] HBOT is a commonly primary or adjunctive medical treatment [ 18 ] and more and more clinical studies suggest it is potentially beneficial to therapy for UC. [ 11 – 13 , 19 , 20 ] Nevertheless, there are no systemic reviews published regarding the effectiveness and safety of HBOT for UC.…”

Carbon Monoxide Poisoning and Chronic Kidney Disease Risk: A Nationwide, Population-Based Study

“…The role of HBOT in COP management remains controversial [19], although some randomized trials suggest a potential benefit of reducing the long-term neurological sequelae [8, 20]. Knowledge on the potential protective effects of HBOT on the kidneys has been restricted to animal models with AKI [21, 22]. Whether HBOT has long-term beneficial effects on kidney outcomes in humans remains unknown.…”