Progesterone ameliorates diabetic nephropathy in streptozotocin-induced diabetic Rats

Abstract

BackgroundPrevious studies reported that 17β-estradiol may influence the progression of diabetic renal disease in females. The present study was intended to provide an insight into the specific effects of progesterone, the other female sex hormone, in the diabetic renal complications.MethodsAdult female wistar rats were divided into four groups (n = 6/group): intact control (non-diabetic, ND), intact diabetic (D), ovariectomized diabetic (D-OVX) and ovariectomized diabetic which were treated with progesterone (D-OVX + P; 10 mg/kg, s.c, every second day) for 10 weeks. Diabetes was induced by a single dose injection of 55 mg/kg streptozotocin. Expressions of transforming growth factor-β (TGF-β), fibronectin, vascular endothelial growth factor-A (VEGF-A), angiotensin II type 1 receptor (ATR1) and podocyte markers (nephrin and podocin) were assessed by immunohistochemistry and real-time PCR.ResultsThe treatment of D-OVX rats with progesterone attenuated diabetic-associated increases in the urinary albumin to creatinine ratio, glomerulosclerosi and the expression of profibrotic and angiogenic factors (TGF-β, Fibronectin and VEGF-A). Furthermore, progesterone supplementation prevented diabetes-induced downregulation of nephrin and podocin while the overexpression of ATR1 in the diabetic rats was inhibited by the progesterone supplementation.ConclusionThese results provided evidence, for the first time, that the replacement of progesterone can ameliorate the renal damage in the experimental models of diabetic nephropathy through improving the renal function; the inhibition of renal fibrosis and abnormal angiogenesis; along with the amelioration of podocyte injury. Additionally, the blocking of renin-angiotensin system through the down-regulation of ATR1 expression may also account for the reno-protective effect of progesterone.Electronic supplementary materialThe online version of this article (doi:10.1186/s13098-015-0097-1) contains supplementary material, which is available to authorized users.

Eugenol ameliorates renal damage in streptozotocin‐induced diabetic rats

“…Male Sprague‐Dawley rats were rendered diabetic using a single dose of streptozotocin (STZ) (55 mg kg ‐1 , i.p. ) after fasting for 8 h . Solution of STZ was prepared by dissolving in ice cold sodium citrate buffer (0.01 M, pH 4.4).…”

“…Male Sprague-Dawley rats were rendered diabetic using a single dose of streptozotocin (STZ) (55 mg kg -1 , i.p.) after fasting for 8 h. [23][24][25] Solution of STZ was prepared by dissolving in ice cold sodium citrate buffer (0.01 M, pH 4.4). Plasma glucose levels were measured after 48 h of STZ administration and animals with plasma glucose level more than 16.7 mmol l -1 were selected for the study.…”

Therapeutic angiogenesis by vascular endothelial growth factor supplementation for treatment of renal disease

“…In DN, the increase in VEGF-A occurs with a lower eNOS activity, resulting in a decoupling of VEGF-A and nitric oxide (66,67). In a similar streptozotocin model, the administration of progesterone to ovariectomized rats resulted in significantly improved renal function that was associated with marked decreases in TGFβ, CTGF, and VEGF mRNA levels as well as increased mRNA levels of podocin and nephrin (68). Given these results and the commonality of VEGF to both of these pathways, VEGF and VEGF-R2 are further supported as potential therapeutic targets, and given that both heightened expression or knockout lead to increased glomerular dysfunction in DN, it is likely that maintenance of VEGF-A activity levels within the normal range during disease onset could prove an effective therapeutic option (54,65).…”

Greater efficacy of atorvastatin versus a non-statin lipid-lowering agent against renal injury: potential role as a histone deacetylase inhibitor

“…In this regard, significant reductions in the renal pro-inflammatory cytokines IL-6 and IL-18 genes were found in AT and EZT groups, relative to untreated DM rats (Supplementary Figure 4). In addition, attenuation of oxidative stress has been suggested as a potential mechanism for renoprotection by other agents such as biotin and progesterone replacement in DM rats without affecting glucose metabolism4647. However, it could be something entirely different that both drugs just happen to do, e.g., reduce BP, or just a coincidence that both drugs, by independent means, affect a particular parameter in a similar way.…”