L-NAME Administration Enhances Diabetic Kidney Disease Development in an STZ/NAD Rat Model.
Raphaëlle CorremansPatrick C D'HaeseBenjamin A VervaetAnja VerhulstPublished in: International journal of molecular sciences (2021)
One of the most important risk factors for developing chronic kidney disease (CKD) is diabetes. To assess the safety and efficacy of potential drug candidates, reliable animal models that mimic human diseases are crucial. However, a suitable model of diabetic kidney disease (DKD) is currently not available. The aim of this study is to develop a rat model of DKD by combining streptozotocin and nicotinamide (STZ/NAD) with oral N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME) administration. Diabetes was induced in male Wistar rats by intravenous injection of 65 mg/kg STZ, 15 min after intraperitoneal injection of 230 mg/kg NAD. Rats were assigned to different groups receiving L-NAME (100 mg/kg/day) (STZ/NAD/L-NAME) or vehicle (STZ/NAD) for a period of 9 or 12 weeks by daily oral gavage. All rats developed hyperglycemia. Hyperfiltration was observed at the start of the study, whereas increased serum creatinine, albumin-to-creatinine ratio, and evolving hypofiltration were detected at the end of the study. Daily L-NAME administration caused a rapid rise in blood pressure. Histopathological evaluation revealed heterogeneous renal injury patterns, which were most severe in the STZ/NAD/L-NAME rats. L-NAME-induced NO-deficiency in STZ/NAD-induced diabetic rats leads to multiple characteristic features of human DKD and may represent a novel rat model of DKD.
Keyphrases
- diabetic rats
- oxidative stress
- chronic kidney disease
- type diabetes
- blood pressure
- cardiovascular disease
- endothelial cells
- physical activity
- emergency department
- risk assessment
- metabolic syndrome
- induced pluripotent stem cells
- climate change
- ultrasound guided
- heart rate
- wound healing
- high dose
- single cell
- end stage renal disease
- skeletal muscle
- quantum dots
- hypertensive patients
- pluripotent stem cells
- adverse drug