Combining streptozotocin and unilateral nephrectomy is an effective method for inducing experimental diabetic nephropathy in the ‘resistant’ C57Bl/6J mouse strain

Abstract

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease. Animal models are essential tools for designing new strategies to prevent DN. C57Bl/6 (B6) mice are widely used for transgenic mouse models, but are relatively resistant to DN. This study aims to identify the most effective method to induce DN in a type 1 (T1D) and a type 2 diabetes (T2D) model in B6 mice. For T1D-induced DN, mice were fed a control diet, and randomised to streptozotocin (STZ) alone, STZ+unilateral nephrectomy (UNx), or vehicle/sham. For T2D-induced DN, mice were fed a western (high fat) diet, and randomised to either STZ alone, STZ+UNx, UNx alone, or vehicle/sham. Mice subjected to a control diet with STZ +UNx developed albuminuria, glomerular lesions, thickening of the glomerular basement membrane, and tubular injury. Mice on control diet and STZ developed only mild renal lesions. Furthermore, kidneys from mice on a western diet were hardly affected by diabetes, UNx or the combination. We conclude that STZ combined with UNx is the most effective model to induce T1D-induced DN in B6 mice. In our hands, combining western diet and STZ treatment with or without UNx did not result in a T2D-induced DN model in B6 mice.

Sitagliptin ameliorates renal tubular injury in diabetic kidney disease via STAT3‐dependent mitochondrial homeostasis through SDF‐1α/CXCR4 pathway

“…However, most diabetic animal models do not develop significant tubular cell injury. Therefore, in this study, we used a STZ‐induced diabetic mice in a susceptible background (DBA2/J) with unilateral nephrectomy 31‐33 . Significant tubular injury was observed in these mice, allowing us to study the mechanism of the renal protective effects of DPP4 inhibitors on tubular cell injury of DKD.…”

“…DBA2/J (D2) male mice were purchased from Beijing HFK Bioscience and housed under a constant 12‐h light‐dark cycle and allowed free access to food and water in the SPF room. The D2 mice were subjected to right unilateral nephrectomy under anesthesia at the age of 6 weeks as described previously 31‐33 . After 2 weeks of observation and recovery, the D2 mice with unilateral nephrectomy were then randomly divided into four experimental groups (n = 10): a control group, a STZ‐induced diabetic group, a control group with Sita supplementation, and a diabetic group with Sita supplementation.…”

The role of activation of KАTP channels on hydrogen sulfide induced renoprotective effect on diabetic nephropathy

“…">Control group: The rats received orally 1 ml of vehicle (ethanol) for 7 days through a gastric tube. Streptozotocin (STZ)‐induced diabetic group (DN): STZ (Sigma) injected intraperitoneal in rats; STZ dose was 50 mg·kg −1 , which is dissolved in citrate buffer with pH (4.5) after overnight fasting (Uil et al, ). To overwhelm the hypoglycemic mortality induced initially by the drug, the STZ‐injected animals allowed to drink 20% glucose solution for 24 hr.…”

“…injected intraperitoneal in rats; STZ dose was 50 mg·kg −1 , which is dissolved in citrate buffer with pH (4.5) after overnight fasting (Uil et al, 2018). To overwhelm the hypoglycemic mortality induced initially by the drug, the STZ-injected animals allowed to drink 20% glucose solution for 24 hr.…”

Platelet inhibition by ticagrelor is protective against diabetic nephropathy in mice

“…Samples were further prepared and glomerular basement membrane (GBM) thickness was measured as previously described. 22 The percentage of effaced podocytes was scored by a pathologist in 10-15 images of the GBM, fusion of foot processes was incorporated in the same score. Glomerular endothelial cell injury, comprising endothelial swelling/hypertrophy and loss of fenestrations were scored by a dedicated renal pathologist.…”