Pioglitazone AND kidney

BACKGROUND: Fragility fractures are increasingly recognized as a complication of type 2 diabetes mellitus (T2DM). The FRAX-Port® is a calculation tool that assesses the 10-year risk of either major and hip fracture, integrating several clinical risk factors, including T2DM. We aimed to evaluate the fracture risk in adults with T2DM and determine the rate of patients at high risk for fracture under anti-osteoporotic therapy. METHODS: We developed a cross-sectional study, including a convenience sample of adults with T2DM, followed in our tertiary center between 2019 and 2022...

The failure of arteriovenous fistulas (AVFs) following intimal hyperplasia (IH) increases morbidity and mortality rates in patients undergoing hemodialysis for chronic kidney disease. The peroxisome-proliferator associated receptor (PPAR-γ) may be a therapeutic target in IH regulation. In the present study, we investigated PPAR-γ expression and tested the effect of pioglitazone, a PPAR-γ agonist, in different cell types involved in IH. As cell models, we used Human Endothelial Umbilical Vein Cells (HUVEC), Human Aortic Smooth Muscle Cells (HAOSMC), and AVF cells (AVFCs) isolated from (i) normal veins collected at the first AVF establishment (T0), and (ii) failed AVF with IH (T1)...

Despite the advancements in the management of Diabetes mellitus, the design and synthesis of drug molecule which ameliorates the hyperglycemia and associated secondary complications in diabetic patients, still remains a challenge. Herein, we report the synthesis, characterization and anti-diabetic evaluation of pyrimidine-thiazolidinedione derivatives. The synthesized compounds were characterized by 1 H NMR, 13 C NMR, FTIR and Mass Spectroscopic analytical techniques. The in-silico ADME studies depicted that the compounds were within the permissible limits of the Lipinski's rule of five...

BACKGROUND: Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the development of proteinuria, whereas peroxisome proliferator-activated receptor ɣ (PPARɣ) agonists can ameliorate proteinuria. Since a recent study showed that PPARɣ regulates HPSE expression in liver cancer cells, we hypothesized that PPARɣ agonists exert their reno-protective effect by inhibiting glomerular HPSE expression...

Ischemia/reperfusion- (I/R-) induced injury is unavoidable and a major risk factor for graft failure and acute rejection following kidney transplantation. However, few effective interventions are available to improve the outcome due to the complicated mechanisms and lack of appropriate therapeutic targets. Hence, this research aimed to explore the effect of the thiazolidinedione (TZD) compounds on I/R-induced kidney damage. One of the main causes of renal I/R injury is the ferroptosis of renal tubular cells...

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease that leads to eventual renal failure. Metformin (MET), an AMP-activated protein kinase (AMPK) activator already approved for type 2 diabetes, is currently investigated for ADPKD treatment. However, despite high tolerability, MET showed varying therapeutic efficacy in preclinical ADPKD studies. Thus, newer strategies have combined MET with other ADPKD small molecule drug candidates, thereby targeting multiple ADPKD-associated signaling pathways to enhance therapeutic outcomes through potential drug synergy...

Acute kidney injury (AKI) is commonly a result of renal ischemia reperfusion injury (IRI), which produces clinical complications characterized by the rapid deterioration of renal function, leading to chronic kidney disease and increases the risk of morbidity and mortality. Currently, only supportive treatment is available. AKI, which is accompanied by immune activation and inflammation, is caused by proximal tubular injury. The present study investigated the role of tubular epithelial cells as drivers of inflammation in renal IRI and their potential function as antigen-presenting cells, as well as the molecular mechanisms by which peroxisome proliferator-activated receptor-γ (PPARγ) agonists [such as pioglitazone (Pio)] exert reno-protective action in renal IRI...

This study examined the influence of PPARG activation by pioglitazone (PG) on the mRNA of core clock, inflammation- and metabolism-related genes in the mouse kidney medulla as well as urinary sodium/potassium excretion rhythms disrupted by reverse feeding. Mice were assigned to daytime feeding and nighttime feeding groups. PG 20 mg/kg was administered at 7 am or 7 pm. On day 8 of the feeding intervention, mice were killed at noon and midnight. Kidney medulla expression of Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, Per2, Nfe2l2, Pparg, and Scnn1g was determined by qRT PCR...

AIM: Elevated fibroblast growth factor-23 (FGF23) is an established marker of cardiovascular disease among patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD). Recently, circulating FGF23 positively correlated with insulin resistance level among patients with CKD. Pioglitazone improves insulin sensitivity and it may have potential for treating CKD-related FGF23 overactivity. METHODS: A randomized, open-label, controlled trial was performed among patients with T2DM and CKD...

Thiazolidinedione (TZD) based medications have demonstrated to enhance the insulin sensitivity control, hyperglycemia, and lipid metabolism in patients with type 2 diabetes. Hence, in this study, a new series of novel coumarin-4-yl-1,2,3-triazol-4-yl-methyl-thiazolidine-2,4-diones (TZD1-TZD18) were synthesized via copper (I)-catalyzed azide-alkyne cycloaddition "Click Chemistry". The synthesized compounds were evaluated for their glucose uptake assay and in vitro cytotoxicity against HEK-293 (human embryonic kidney) cells which were compared with the standard drug Pioglitazone...

Podocytes are highly differentiated epithelial cells, and their structural and functional integrity is compromised in a majority of glomerular and renal diseases, leading to proteinuria, chronic kidney disease, and kidney failure. Traditional agonists (e.g., pioglitazone) and selective modulators (e.g., GQ-16) of peroxisome-proliferator-activated-receptor-γ (PPARγ) reduce proteinuria in animal models of glomerular disease and protect podocytes from injury via PPARγ activation. This indicates a pivotal role for PPARγ in maintaining glomerular function through preservation of podocytes distinct from its well-understood role in driving insulin sensitivity and adipogenesis...

Diabetic kidney disease (DKD) is described in approximately 20-40% of all diabetic patients and is associated with significant cardiovascular and all-cause mortality. The involvement of multiple metabolic, haemodynamic, inflammatory, and tubular pathways in the pathophysiology of DKD generates the need for multitargeted treatment approaches to improve its development at all levels and delay or even reverse its progression. Thiazolidinediones are potent exogenous agonists of PPAR-γ, which augment the effects of insulin on its cellular targets, mainly at the level of adipose tissue...

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the United States and worldwide. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), is a leading indication for liver transplant. Comorbidities associated with NAFLD development and NASH include type 2 diabetes, obesity, metabolic syndrome, and dyslipidemia. Extrahepatic morbidity and mortality are considerable as NAFLD is associated with an increased risk of cardiovascular disease and chronic kidney disease...

BACKGROUND: Nephrotic syndrome (NS) is a common pediatric kidney disease, yet current treatments for complicated NS are only partially effective and have significant toxicity. There is no Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-approved safe and effective treatment for NS. Thiazolidinediones (TZDs) have been shown to reduce proteinuria in both diabetic and non-diabetic kidney disease and in preclinical studies to directly protect podocytes from injury and reduce proteinuria...

Insulin resistance (IR) is a condition in which target cells become insensitive to normal insulin concentrations in order to deliver glucose. The goal of this study was to see if solasodine combined with coenzyme Q10 could help rats with insulin resistance caused by a high-fat diet (HFD) by regulating the expression of IRS-I and PPAR-γ proteins.One of the six groups (n=6) got a conventional diet for 16 weeks as a control (normal), the HFD was given to the other five groups for 16 weeks, which further classified as-one group as HFD control while others treated with pioglitazone (10 mg/kg), coenzyme Q10 (50 mg/kg), solasodine (50 mg/kg) and combination of solasodine and coenzyme Q10i...

A sudden decrease in the functionality of the kidney with concomitant structural damage and functional loss is known as acute kidney injury (AKI), with some of the potential causes having to do with a focal mismatch between oxygen and nutrient delivery to the nephrons. Increased energy demands on account of cellular stress is another cause [Kellum et al 2021]. AKI occurs when renal function is acutely decreased, so waste products accumulate within the body, making the body unable to maintain electrolyte, acid-base, and water balance [Bhatraju et al 2020]...

A bioanalytical method for the quantification of rosiglitazone in rat plasma and tissues (adipose tissue, heart, brain, bone, and kidney) using LC-MS/MS was developed and validated. Chromatographic separation was achieved on a Gemini C18 column (50 × 4.6 mm, 3 μm) using a mobile phase consisting of 10 mM ammonium formate (pH 4.0) and acetonitrile (10:90, v/v) at a flow rate of 0.8 mL/min and injection volume of 10 μL (internal standard: pioglitazone). LC-MS detection was performed with multiple reaction monitoring mode using target ions at m/z → 358...

AIMS: The nephrotoxicity of cyclosporine A (CsA) limits its use as an immunosuppressant. Wnt/β-catenin signaling is involved in the pathogenesis of both acute and chronic kidney disease, and it is inhibited by peroxisome proliferator-activated receptor gamma (PPARγ). We aimed to evaluate if geraniol, which can modulate both PPARγ and Wnt signaling, could protect against CsA-induced nephrotoxicity. MATERIALS AND METHODS: Rats (6 groups) received the vehicle or a combination of CsA (30 mg/kg) with the vehicle, geraniol (50, 100, or 200 mg/kg), or the PPARγ agonist pioglitazone for 4 weeks...

PURPOSE: Plukenetia conophora (African walnut) is an edible seed, widely cultivated for its ethnomedicinal and nutritional purposes. Consumption of African walnuts has been linked with blood sugar lowering effect. OBJECTIVE: The effects of P. conophora seed oil treatment on hyperglycemia and oxidative stress were investigated in plasma, liver and kidney of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Plukenetia conophora seed oil (PCO) was obtained by extraction of pulverized dried seed in n-hexane...

Post-transplant diabetes mellitus (PTDM) is a significant contributor to morbidity and mortality in liver transplant recipients (LTRs). With concurrent comorbidities and use of various immunosuppression medications, identifying a safe and personalized regimen for management of PTDM is needed. There are many comorbidities associated with the post-transplant course including chronic kidney disease, cardiovascular disease, allograft steatosis, obesity, and de novo malignancy. Emerging data suggest that available diabetes medications may carry beneficial or, in some cases, harmful effects in the setting of these co-existing conditions...