Effect of curcumin on acute chronic kidney disease due to ischemia-reperfusion syndrome / Efecto de la curcumina en la enfermedad renal crónica agravada por el síndrome de isquemia-reperfusión / Efeito da curcumina na doença renal crônica agudizada pela síndrome isquemia-reperfusão

ABSTRACT Objective: To evaluate the effect of curcumin on renal function, hemodynamics, and renal oxidative profile of rats with chronic kidney disease (CKD) subjected to renal ischemia-reperfusion injury (IRI). Methods: Wistar rats, 250-300 g, distributed in four groups: Sham (n = 5), CKD simulation; CKD (n = 5), 5/6 renal ablation for CKD induction; CKD + IRI (n = 5), CKD and renal pedicle clamping for 30 minutes; and CKD + IRI+curcumin (n = 5), CKD + IRI, curcumin administration 30 mg/kg/day, orally, for 10 days. Renal function (inulin clearance, urine flow, plasma creatinine), hemodynamics (blood pressure), and oxidative profile (peroxides, TBARS, and urine nitrate, non-protein soluble thiols in renal tissue) were evaluated. Results: The CKD + IRI + curcumin group showed increased inulin clearance and reduced plasma creatinine, decreased RVR and increased RBF, decreased oxidative metabolites in urine and increased thiols in renal tissue when compared with the CKD + IRI group. Conclusion: The treatment with curcumin preserved renal function and hemodynamics of animals with acute CKD, improving oxidative profile, with reduction of oxidants and preservation of antioxidant reserve.

RESUMEN Objetivo: Evaluar el efecto de la curcumina sobre la función renal, hemodinámica y el perfil oxidativo renal en ratas con enfermedad renal crónica (ERC) sometidas a isquemia-reperfusión renal (I/R). Métodos: Ratas Wistar, entre 250-300 g, divididas en cuatro grupos: Sham (n = 5), simulación de ERC; ERC (n = 5), ablación de 5/6 de los riñones para inducción de ERC; ERC + I/R (n = 5), ERC y pinzamiento del pedículo renal durante 30 minutos; y ERC + I/R + curcumina (n = 5) y ERC + I/R, administración de curcumina 30 mg/kg/día, vía oral, durante 10 días. Se evaluaron la función renal (clearance de inulina, flujo urinario, creatinina plasmática), hemodinámica (presión arterial) y el perfil oxidativo (peróxidos, TBARS y nitrato urinario, tioles solubles no proteicos en tejido renal). Resultados: El grupo ERC + I/R + curcumina tuvo un aumento en el clearance de inulina y disminución de creatinina plasmática, disminución de la RVR y aumento del FSR, disminución de metabolitos oxidativos en orina y aumento de tioles en el tejido renal en comparación con el grupo ERC + I/R. Conclusión: El tratamiento con curcumina preservó la función renal y la hemodinámica de los animales con ERC agravada, promoviendo una mejora en el perfil oxidativo, con reducción de oxidantes y preservación de la reserva antioxidante.

RESUMO Objetivo: Avaliar o efeito da curcumina na função renal, hemodinâmica e perfil oxidativo renal de ratos com doença renal crônica (DRC) submetidos a isquemia-reperfusão renal (I/R). Métodos: Ratos Wistar, 250-300 g, distribuídos em quatro grupos: Sham (n = 5), simulação da DRC; DRC (n = 5), ablação de 5/6 dos rins para indução de DRC; DRC + I/R (n = 5), DRC e clampeamento do pedículo renal por 30 minutos; DRC + I/R + curcumina (n = 5) e DRC + I/R, administração de curcumina 30 mg/kg/dia, via oral, por 10 dias. Foram avaliadas a função renal (clearance de inulina, fluxo urinário, creatinina plasmática), hemodinâmica (pressão arterial) e perfil oxidativo (peróxidos, TBARS e nitrato urinário, tióis solúveis não proteicos no tecido renal). Resultados: O grupo DRC + I/R + curcumina apresentou elevação do clearance de inulina e redução da creatinina plasmática, diminuição da RVR e aumento do FSR, diminuição de metabólitos oxidativos na urina e aumento dos tióis no tecido renal quando comparado ao grupo DRC + I/R. Conclusão: O tratamento com curcumina preservou a função e hemodinâmica renal dos animais com DRC agudizada, promovendo melhora no perfil oxidativo, com redução de oxidantes e preservação de reserva antioxidante.

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

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.