Protective effect of pioglitazone on kidney injury in diabetic rats

Peng, Xiaohui; Liang, Ping; Ou, Shan-Ji; Zu, Xiongbing

doi:10.1016/s1995-7645(14)60143-7

Cited by 8 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in this study, administration of pioglitazone significantly decreased serum creatinine levels, microalbuminuria, and renal alternations. These findings are in line with those of previous studies, where administration of pioglitazone significantly reduced albuminuria and regressed development of histopathological lesions and vascular wall consolidation [22,23,32]. These beneficial effects of pioglitazone might be related to decreased levels of malondialdehyde, superoxide dismutase, interleukin-6, and tumor necrosis factor alpha [1,23], which was confirmed in the present work.…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Effects of Pioglitazone and Irbesartan on Endothelial Dysfunction on Experimentally Streptozotocin-Induced Diabetic Nephropathy in Rats

Attallah

Ibrahim

Elnaggar

2018

Egyptian Journal of Basic and Clinical Pharmacology

View full text Add to dashboard Cite

Background and Aim. Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED) that leads to the pathogenesis of diabetic nephropathy (DN). Diabetic nephropathy (DN) is a main cause of end stage renal disease. This study was designed to investigate the protective effects of irbesartan (IRB) and its combination with pioglitazone (PIO) on impaired endothelial dysfunction, oxidative stress, and inflammation beyond blood glucose control in streptozotocin-(STZ-) induced diabetic nephropathy in rats. Materials and Methods. Forty-eight male albino rats were divided equally and randomly into six groups: A (control nondiabetic non-treated) and B (diabetic non-treated) injected intraperitoneally by streptozotocin (65mg/kg) and nicotinamide (110 mg/kg) to induce diabetic nephropathy; C (diabetic treated with IRB (30mg/kg/daily) orally), D (diabetic treated with PIO (30mg/kg/daily) orally) , E (diabetic treated with IRB and PIO in doses (30 mg/kg/day and 30 mg/kg/day) orally), and F (diabetic treated with IRB and PIO in doses (5mg/kg/day and 15mg/kg/day, resp.) orally for 12 weeks). Fasting blood glucose, urea, creatinine, albumin in urine levels, IL-6, nitric oxide (NO), and Malondialdehyde peroxidase (MDA) were determined in serum of the different groups at the end of the experiment; renal blood flow and aortic and renal histopathological changes were also evaluated. Results. Administration of irbesartan and pioglitazone to diabetic rats caused significant decrease in levels of urea, creatinine, albumin, serum inflammatory mediators (IL-6 and NO), and oxidative stress markers. The effects of irbesartan and/or pioglitazone were associated with improvement of renal blood flow, and they markedly reduced vascular and renal damage induced by diabetes. Conclusion. The results of the present study support the fact that the combination between irbesartan and pioglitazone was better than monotherapy on endothelial dysfunction and diabetic nephropathy through inhibition of the pro-inflammatory mediators, NO bioavailability, and oxidative stress, which are independent of their glucoselowering properties. And there was no significant difference between the combination of pioglitazone and irbesartan in large doses and in low doses.

show abstract

Section: Discussionsupporting

confidence: 93%

“…PPARy receptors are found in vascular smooth muscle cells, macrophages vascular endothelial cells, colonic epithelial cells, and renal glomerular cells [34]. Beneficial effects of thiazolidinedione on diabetic nephropathy have been reported [23,32].…”

Section: Introductionmentioning

confidence: 99%

Effects of Pioglitazone and Irbesartan on Endothelial Dysfunction on Experimentally Streptozotocin-Induced Diabetic Nephropathy in Rats

Attallah

Ibrahim

Elnaggar

2018

Egyptian Journal of Basic and Clinical Pharmacology

View full text Add to dashboard Cite

show abstract

“…Previous studies have demonstrated that rosiglitazone could protect kidney from damage induced by several factors ( Huang et al, 2013 ; Kumar et al, 2013 ; Korolczuk et al, 2014 ). Pioglitazone attenuated renal ischemia-reperfusion injury through its anti-inflammatory and antioxidant effects ( Reel et al, 2013 ; Zou et al, 2013 ), reduced kidney damage in diabetic rats through increasing glomerular podocalyxin protein expression ( Peng et al, 2014 ) and provided renoprotection by interfering with the renin-angiotensin system and profibrotic proteins ( Ochodnicky et al, 2014 ). In addition, mitochondria are a target of PPARγ agonists.…”

Section: Introductionmentioning

confidence: 99%

Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats

Sun

Yuan

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ) agonist and has been demonstrated to be effective in chronic kidney diseases (CKD) treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx) rats and TGF-β1-exposed HK-2 cells. Pioglitazone attenuated renal injury and improved renal function, as examined by 24 h urinary protein, blood urea nitrogen and plasma creatinine in Nx rats. Renal fibrosis and enhanced expressions of profibrotic proteins TGF-β1, fibronectin and collagen I caused by Nx were significantly alleviated by pioglitazone. In addition, pioglitazone protected mitochondrial functions by stabilizing the mitochondrial membrane potential, inhibiting ROS generation, maintaining ATP production and the activities of complexes I and III, and preventing cytochrome C leakage from mitochondria. Pioglitazone also upregulated the expression levels of ATP synthase β, COX I and NDUFB8, which were downregulated in the kidney of Nx rats and TGF-β1-exposed HK-2 cells. Furthermore, pioglitazone increased fusion proteins Opa-1 and Mfn2 expressions and decreased fission protein Drp1 expression. The results imply that pioglitazone may exert the renoprotective effects through modulating mitochondrial electron transport chain and mitochondrial dynamics in CKD. Finally, these recoveries were completely or partly inhibited by GW9662, which suggests that these effects at least partly PPARγ dependent. This study provides evidence for the pharmacological mechanism of pioglitazone in the treatment of CKD.

show abstract

“…In the recent past, the anti‐oxidant and anti‐inflammatory functions of PPAR‐γ have received major attention. Administration of PPAR‐γ agonists, like pioglitazone and rosiglitazone, protected against ischemia reperfusion‐induced AKI, diabetic nephropathy, and drug‐induced kidney injury (Al‐Azzam, Abdul‐Razzak, & Jaradat, 2010; Jesse et al, 2014; Peng, Liang, Ou, & Zu, 2014; Singh, Singh, & Bedi, 2016). PPAR‐γ regulates the activity of glucose transporter‐4 (GLUT‐4), which further allows glucose entry inside the cells.…”

Section: Introductionmentioning

confidence: 99%

Stevioside protects against rhabdomyolysis‐induced acute kidney injury through PPAR‐γ agonism in rats

Kaur

Singh

et al. 2020

Drug Development Research

View full text Add to dashboard Cite

We explored the potential role of peroxisome proliferator activated receptor‐γ (PPAR‐γ) in stevioside‐mediated renoprotection using rhabdomyolysis‐induced acute kidney injury (AKI) model in rats. Rhabdomyolysis refers to intense skeletal muscle damage, which further causes AKI. Glycerol (50% w/v, 8 ml/kg) was injected intramuscularly in rats to induce rhabdomyolysis. After 24 hr, AKI was demonstrated by quantifying serum creatinine, urea, creatinine clearance, microproteinuria, and electrolytes in rats. Further, oxidative stress was measured by assaying thiobarbituric acid reactive substances, generation of superoxide anion, and reduced glutathione levels. Additionally, serum creatine kinase (CK) level was assayed to determine glycerol‐induced muscle damage in rats. Pathological changes in rat kidneys were studied using hematoxylin–eosin and periodic acid Schiff staining. Moreover, the expression of apoptotic markers (Bcl‐2, Bax) in rat kidneys was demonstrated by immunohistochemistry. Stevioside (10, 25, and 50 mg/kg) was administered to rats, prior to the induction of AKI. In a separate group, bisphenol A diglycidyl ether (BADGE, 30 mg/kg), a PPAR‐γ receptor antagonist was given prior to stevioside administration, which was followed by rhabdomyolysis‐induced AKI in rats. The significant alteration in biochemical and histological parameters in rats indicated AKI, which was attenuated by stevioside treatment. Pretreatment with BADGE abrogated stevioside‐mediated renoprotection, which is suggestive of the involvement of PPAR‐γ in its renoprotective effect. In conclusion, stevioside protects against rhabdomyolysis‐induced AKI, which may be attributed to modulation of PPAR‐γ expression.

show abstract

Protective effect of pioglitazone on kidney injury in diabetic rats

Abstract: Pioglitazone can reduce kidney damage in diabetic rats, which may be attributed to its role in increasing glomerular PCX protein expression and inhibiting urinary excretion of PCX, and its effect is dose dependent.

Cited by 8 publications

References 20 publications

Effects of Pioglitazone and Irbesartan on Endothelial Dysfunction on Experimentally Streptozotocin-Induced Diabetic Nephropathy in Rats

Effects of Pioglitazone and Irbesartan on Endothelial Dysfunction on Experimentally Streptozotocin-Induced Diabetic Nephropathy in Rats

Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats

Stevioside protects against rhabdomyolysis‐induced acute kidney injury through PPAR‐γ agonism in rats

Contact Info

Product

Resources

About