Abstract
OBJECTIVES:Contrast-induced acute kidney injury (CI-AKI) is an important clinical problem that can be aggravated by diabetes mellitus, a major risk factor. However, heme oxygenase-1 (HO-1), a promising therapeutic target, can exert antioxidant effects against CI-AKI. Thus, we investigated the role of HO-1 in CI-AKI in the presence of diabetes mellitus.METHODS:Twenty-eight male Wistar rats weighing 250-300g were subjected to left uninephrectomy, and concomitantly, diabetes induced by streptozotocin (65 mg/kg). After 12 weeks, iodinated contrast (meglumine ioxithalamate, 6 mL/kg) and hemin (HO-1 inducer-10 mg/k) were administered 60 min before iodinated contrast treatment. The rats were randomly divided into four groups: control, diabetes mellitus (DM), DM iodinated contrast (DMIC), and DMIC hemin (DMICH). Kidney function, albuminuria, oxidative profile, and histology were assessed. All experimental data were subjected to statistical analyses.RESULTS:CI-AKI in preclinical diabetic models decreased creatinine clearance and increased urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and the degree of albuminuria. Additionally, the levels of oxidative and nitrosative stress metabolites (urinary peroxides, thiobarbituric acid-reactive substances, and NO) were elevated, while thiol levels in kidney tissue were reduced. Kidney histology showed tubular cell vacuolization and edema. HO-1 inducer treatment improved kidney function and reduced urinary the NGAL levels. The oxidative profile showed an increase in the endogenous thiol-based antioxidant levels. Additionally, the tubular injury score was reduced following HO-1 treatment.CONCLUSIONS:Our findings highlight the renoprotective effects of HO-1 in CI-AKI and preclinical diabetic models. Therefore, HO-1 ameliorates kidney dysfunction, reduces oxidative stress, and prevents cell necrosis.
Highlights
Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic syndrome that arises after iodinated contrast (IC) administration, which is used to perform diagnostic imaging tests such as cardiac catheterization [1,2]
We aimed to investigate the protective effects of heme oxygenase-1 (HO-1) on CI-AKI in diabetic rats by analyzing metabolic functions, oxidative profile, and histopathological staining
Treatment with hemin prevented the decrease in GFR, demonstrating the renoprotective action of HO-1 in the DMIC hemin (DMICH) group, compared to the case for the control DM iodinated contrast (DMIC) group
Summary
Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic syndrome that arises after iodinated contrast (IC) administration, which is used to perform diagnostic imaging tests such as cardiac catheterization [1,2]. Its incidence varies from 3% to 19%, but risk factors such as chronic kidney disease, advanced age, and diabetes mellitus (DM) can increase it to 26% [3,4,5]. In this context, DM is associated with. Received for publication on March 30, 2021. Accepted for publication on September 14, 2021
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