Heme Oxygenase-1 counteracts contrast-induced acute kidney injury in diabetic rats via antioxidant pathway
Contrast-induced acute kidney injury (CI-AKI) is the third leading cause of hospital-acquired kidney injury. Diabetes Mellitus is an important risk factor for contrast-induced acute kidney injury and its identification is predictable. Heme oxygenase-1 (HO-1) is a new therapeutic target that exerts antioxidant effect against kidney diseases. This study investigated the effect of HO-1 on metabolic functions, oxidative profile and morphology at CI-AKI in the presence of Diabetes Mellitus. Twenty-eight male Wistar rats weighing 250-300g were randomized into four groups: C (control)- rats submitted to left uninephrectomy on the 1th day; DM- Diabetes was induced by a single dose of intravenous streptozotocin-65mg/kg on the 20th day; DMIC- iodinated contrast- meglumine ioxithalamate (6ml/kg, intraperitoneal, once) rats and DMICH- hemin (HO-1 inducer; 10mg/kg; intraperitoneal; 60 minutes before iodinated contrast) were infused on the 85th day. Diabetic groups showed polyphagia, polydipsia, polyuria, and increase in the blood glucose and in the kidney/animal weight ratio. Iodinated contrast reduced the creatinine clearance and thiols in renal tissue with a prominent increase in urinary NGAL, peroxides, oxide nitric and thiobarbituric acid-reactive substances (TBARS), these parameters were significantly changed by HO-1 inducer. Kidney histology showed tubular cells vacuolization and edema in iodinated contrast animals. The data highlight the HO-1 protective effect against contrast-induced AKI associated with chronic disease, DM.