• FonsecaCassiane Dezoti daCDD0000-0002-2118-8562Escola Paulista de Enfermagem, Universidade Federal de Sao Paulo, Sao Paulo, SP, BR.Laboratorio Experimental de Modelos Animais (LEMA), Escola de Enfermagem, Universidade de Sao Paulo, Sao Paulo, SP, BR., Mirian Watanabe, Sheila Marques Fernandes Couto, Alef Aragão Carneiro Dos Santos, Fernanda Teixeira Borges, and VattimoMaria de Fatima FernandesMFF0000-0002-7036-5676Laboratorio Experimental de Modelos Animais (LEMA), Escola de Enfermagem, Universidade de Sao Paulo, Sao Paulo, SP, BR..
• Escola Paulista de Enfermagem, Universidade Federal de Sao Paulo, Sao Paulo, SP, BR.
• Clinics (Sao Paulo). 2021 Jan 1; 76: e3002.

ObjectivesContrast-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.MethodsTwenty-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.ResultsCI-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.ConclusionsOur 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.

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