The renoprotective effects of Heme Oxygenase-1 during contrast-induced acute kidney injury in preclinical diabetic models

Autor(es)

Cassiane Dezoti da Fonseca ; Mirian Watanabe ^[2] ; Sheila Marques Fernandes Couto ^[3] ; Alef Aragão Carneiro dos Santos ^[4] ; Fernanda Teixeira Borges ; Maria de Fatima Fernandes Vattimo ^[6]

• Tipo de documento: Artigo Científico
• Fonte: Clinics; v. 76, 2021-10-18.

Resumo

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. (AU)

• Processo FAPESP: 13/26560-2 - O contraste radiológico em situações de risco para nefropatia
• Beneficiário: Maria de Fatima Fernandes Vattimo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/24028-6 - O efeito do inibidor da fosfodiestarese-5 na lesão renal aguda isquêmica em ratos
• Beneficiário: Mirian Watanabe
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado