Metformin ameliorates diabetic nephropathy in a rat model of low-dose streptozotocin-induced diabetes

Abstract

Abstract. The present study aimed to explore the renoprotective effect of metformin on diabetic nephropathy in type 2 diabetic rats. A rat model of type 2 diabetic nephropathy (T2DN) was successfully induced via a high-fat diet combined with a single low-dose of streptozotocin. Metformin was administered intragastrically for 13 weeks, and fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), HDL-c, LDL-c, urinary and serum creatinine levels were subsequently examined at the end of administration. Renal function was determined after the treatment protocol. Expression levels of transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF) were assessed via immunohistochemical analysis. Superoxide dismutase activity, malondialdehyde content and glutathione peroxidase levels were assessed in kidney tissues using commercially available kits. The results of the present study demonstrated that metformin administration significantly decreased the levels of serum blood urea nitrogen, serum creatinine, creatinine clearance, urinary albumin excretion and fasting blood glucose in rats with T2DN. Furthermore, TG, TC and LDL-c levels were significantly decreased following metformin treatment, whereas HDL-c was increased. Metformin treatment significantly increased SOD activity and significantly decreased malondialdehyde levels, as compared with the model group. It was also demonstrated that metformin administration significantly decreased the expression levels of TGF-β1 and attenuated the morphological changes associated with T2DN in rats. These data clearly demonstrated the renoprotective effects of metformin against the development and progression of T2DN in rats. The underlying mechanism of this protective effect may be associated with glycemic control, lipid metabolism, and anti-oxidative and anti-inflammatory functions.

EFFECTS OF Nigella sativa, Zingiber officinale, Cinnamomum zeylanicum ON SERUM LIPID PROFILE, GLUCOSE, WEIGHT, AND KIDNEY FUNCTION TESTS IN THE ANIMAL MODEL OF STZ INDUCED DIABETES MELLITUS IN MALE RATS

“…Results of treated group of our study regarding reduction in creatinine and urea levels are in conformity with the study conducted by Zhang et al [47]. …”

Stachyose Improves Inflammation through Modulating Gut Microbiota of High‐Fat Diet/Streptozotocin‐Induced Type 2 Diabetes in Rats

“…Serum was collected to analyze LPS, blood glucose, TC, TG, high‐density lipoprotein cholesterol (HDL‐c), LDL‐c, pancreas tissue for gene expression of phosphoinosmde‐3‐kinase (PI3K), protein kinase B (Akt), IL‐2, IL‐6, TNF‐α, TGF‐β, and contents of colon for gut microbiota. Blood biochemical parameters were determined by the Health Science Center of Peking University (Pecking, China) as previously described …”

Metformin attenuates renal medullary hypoxia in diabetic nephropathy through inhibition uncoupling protein‐2

“…However, the present study measured GFR directly by clearance of inulin and estimated filtration barrier integrity from urinary excretion of albumin in order to avoid the commonly acknowledged problems associated with tubular handling of creatinine in rodents . Importantly, previous studies have reported beneficial effects of metformin on DKD when treating for 8 to 13 weeks after the onset of diabetes . In the present study, we investigated the effect of metformin on intrarenal oxygen availability already after 4 weeks of diabetes duration, since we hypothesize that early changes in kidney oxygen metabolism is a crucial component for the onset and progression of DKD.…”

“…The renal medulla is especially sensitive to hypoxia due to low blood perfusion and high basal levels of QO 2. The renoprotective effects of metformin have been reported in several animal studies, including unilateral ureteral obstruction and gentamicin‐induced nephropathy as well as in DKD . Metformin is a drug with pleotropic effects and has been suggested to protect against DKD through AMP‐activated protein kinase/mammalian target of rapamycin modulation, attenuation of hypoxia‐inducible factor 1‐alpha accumulation, and through modulation of oxidative stress‐related gene expression …”