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

Autor(es)

da Fonseca, Cassiane Dezoti ^{[1, 2]} ; Watanabe, Mirian ^[3] ; Fernandes Couto, Sheila Marques ^[2] ; Carneiro Dos Santos, Alef Aragao ^[4] ; Borges, Fernanda Teixeira ^{[5, 4]} ; Fernandes Vattimo, Maria de Fatima ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Enfermagem, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Lab Expt Modelos Anim LEMA, Escola Enfermagem, Sao Paulo, SP - Brazil

^[3] Fac Metropolitanas Unidas FMU, Ctr Univ, Sao Paulo, SP - Brazil

^[4] Univ Cruzeiro Sul, Programa Posgrad Interdisciplinar Ciencias Saude, Sao Paulo, SP - Brazil

^[5] Univ Fed Sao Paulo, Div Nefrol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinics; v. 76, 2021.
• Citações Web of Science: 0

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: 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
• 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