scholarly journals New Insights into the PPARγAgonists for the Treatment of Diabetic Nephropathy

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Zhanjun Jia ◽  
Ying Sun ◽  
Guangrui Yang ◽  
Aihua Zhang ◽  
Songming Huang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Adverse Effects ◽  
Therapeutic Potential ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Cardiovascular Complications ◽  
Therapeutic Strategies ◽  
Peroxisome Proliferator ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Peroxisome Proliferator Activated Receptor

Diabetic nephropathy (DN) is a severe complication of diabetes and serves as the leading cause of chronic renal failure. In the past decades, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) based first-line therapy can slow but cannot stop the progression of DN, which urgently requests the innovation of therapeutic strategies. Thiazolidinediones (TZDs), the synthetic exogenous ligands of nuclear receptor peroxisome proliferator-activated receptor-γ(PPARγ), had been thought to be a promising candidate for strengthening the therapy of DN. However, the severe adverse effects including fluid retention, cardiovascular complications, and bone loss greatly limited their use in clinic. Recently, numerous novel PPARγagonists involving the endogenous PPARγligands and selective PPARγmodulators (SPPARMs) are emerging as the promising candidates of the next generation of antidiabetic drugs instead of TZDs. Due to the higher selectivity of these novel PPARγagonists on the regulation of the antidiabetes-associated genes than that of the side effect-associated genes, they present fewer adverse effects than TZDs. The present review was undertaken to address the advancements and the therapeutic potential of these newly developed PPARγagonists in dealing with diabetic kidney disease. At the same time, the new insights into the therapeutic strategies of DN based on the PPARγagonists were fully addressed.

Can we Overcome the Predestined Poor Survival of Diabetic Patients? Perspectives from Pre- and Post-Dialysis

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 171-175
Author(s):  
Yong-Lim Kim
Keyword(s):  
Degradation Products ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Diabetic Patients ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Angiotensin Ii Receptor ◽  
Poor Survival ◽  
Cvd Risk ◽  
Converting Enzyme Inhibitors ◽  
Peroxisome Proliferator Activated Receptor

Although the survival of diabetic peritoneal dialysis (PD) patients has improved, it is still much worse than the survival of nondiabetic patients. Diabetes has its own risks for cardiovascular disease (CVD), such as increased levels of advanced glycation end-products, carbonyl and oxidative stress, and low-grade inflammation. An independent, graded association has been observed between a reduced glomerular filtration rate and the risk of CVD events in chronic kidney disease (CKD). Both CKD and diabetes synergistically lead to a high risk of CVD. It seems that the poor survival of diabetic PD patients is predestined at the initiation of dialysis because of multiple pre-existing risk factors and comorbid diseases, particularly CVD. Recently, several trials were successful in improving the survival of patients with diabetic CKD. Tight control of glucose, blood pressure management using angiotensin converting-enzyme inhibitors or angiotensin II receptor blockers, and use of statins, antioxidants, or peroxisome proliferator-activated receptor gamma agonists may improve the survival of diabetic PD patients. However, simple correction of a single CVD risk factor is not likely to be effective. New PD solutions such as those low in glucose degradation products or those with icodextrin may also be effective in reducing the risk of CVD in diabetic PD patients. Therefore, multifactorial interventions—including diet control, early referral, and choice of an optimal PD solution—may improve the survival of diabetic PD patients.

Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on pulmonary function in hypertensive patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Azza S. Jabbar ◽  
Nadheera F. Neamah ◽  
Ahmed H. Al-Darraji
Keyword(s):  
Angiotensin Ii ◽  
Adverse Effects ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Hypertensive Patients ◽  
Receptor Blockers

Abstract Objectives Hypertension is a very common cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are widely used to treat hypertension. Many patients with hypertension are vulnerable to the antihypertensive adverse effects, which potentially reduces the adherence rate. Therefore, we conducted this study in order to evaluate the safety profile of both classes (ACEi and ARBs) on respiratory functions. Methods Two main groups of subjects were studied: first group is healthy control subjects and the second group is hypertensive patients, which was subdivided into subgroups in order to investigate the effect of all tested medications (captopril, enalapril, lisinopril, losartan, and valsartan). Respiratory efficiency was evaluated by measuring pulmonary function tests: FEV1, FVC, and FEV1%. Measurements were done using micromedical spirometer. Results We found that ARBs do not impair normal respiratory functions as measured by FEV1, FEV1%, and FVC in hypertensive patients. While ACEi treatments significantly reduced FEV1, FEV1%, and FVC compared to the other groups. Conclusions ARBs are not associated with any harmful effects on respiratory functions in hypertensive patients, unlike ACEi. As such, they could represent a first-choice treatment for hypertensive patients who are at high risk to the respiratory adverse effects.

scholarly journals Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer’s Disease

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Manoj Govindarajulu ◽  
Priyanka D. Pinky ◽  
Jenna Bloemer ◽  
Nila Ghanei ◽  
Vishnu Suppiramaniam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Effects ◽  
Therapeutic Potential ◽  
Protein Accumulation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Continuous Increase ◽  
Therapeutic Benefits ◽  
The Brain

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. The continuous increase in the incidence of AD with the aged population and mortality rate indicates the urgent need for establishing novel molecular targets for therapeutic potential. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists such as rosiglitazone and pioglitazone reduce amyloid and tau pathologies, inhibit neuroinflammation, and improve memory impairments in several rodent models and in humans with mild-to-moderate AD. However, these agonists display poor blood brain barrier permeability resulting in inadequate bioavailability in the brain and thus requiring high dosing with chronic time frames. Furthermore, these dosing levels are associated with several adverse effects including increased incidence of weight gain, liver abnormalities, and heart failure. Therefore, there is a need for identifying novel compounds which target PPARγ more selectively in the brain and could provide therapeutic benefits without a high incidence of adverse effects. This review focuses on how PPARγ agonists influence various pathologies in AD with emphasis on development of novel selective PPARγ modulators.

The Potential Therapeutic Value of Renin-Angiotensin System Inhibitors in the Treatment of Colorectal Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Ehsan Tabatabai ◽  
Majid Khazaei ◽  
Mohammad Reza Parizadeh ◽  
Mohammad Nouri ◽  
Seyed Mahdi Hassanian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Promote Cell Proliferation

: Colorectal cancer is the third most common cancer globally. Despite extensive preclinical and clinical studies, it is still among the leading causes of cancer-related death, and a need for new therapeutic options is required. The renin-angiotensin system plays an important role in regulating blood pressure and cell growth. In addition to their hemodynamic effects, some of the renin-angiotensin system components, such as angiotensin, are also growth factors that promote cell proliferation and angiogenesis, and its dysregulation is reported to be associated with poor prognosis in colorectal cancer. Here we describe the critical role of the renin-angiotensin system pathway in colorectal cancer as well as the preclinical and clinical investigations renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as a potential therapeutic target in the treatment of colorectal cancer. Several studies have been shown that the inhibition of these pathways can reduce tumor growth and metastasis; however, some of the data remain inconsistent. There is accumulating evidence of the therapeutic potential of some inhibitors, such as Losartan which are now in clinical phases in the treatment of several malignancies using Nivolumab in combination with FOLFIRINOX in pancreatic cancer. Further investigations are warranted to improve the efficacy and selectivity of current and future anticancer strategies targeting renin-angiotensin systems.

scholarly journals Glycyrrhizic Acid Prevents Diabetic Nephropathy by Activating AMPK/SIRT1/PGC-1α Signaling in db/db Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Shaozhang Hou ◽  
Ting Zhang ◽  
Yuan Li ◽  
Fengying Guo ◽  
Xiu Jin
Keyword(s):  
Diabetic Nephropathy ◽  
Glycyrrhizic Acid ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Smooth Muscle Actin ◽  
Adenosine Monophosphate ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Peroxisome Proliferator ◽  
Ros Production ◽  
Peroxisome Proliferator Activated Receptor

Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Glycyrrhizic acid (GA) is an effective inhibitor of reactive oxygen species (ROS) production. We investigated the role of GA in the progression of renal injury in DN. Albumin (Alb)/creatinine (crea) levels were significantly lower, and renal histopathology was attenuated in the diabetic db/db mice that were treated with GA (15 mg/kg via intraperitoneal injection) once per day for eight weeks. These changes were associated with significantly lower levels of α-smooth muscle actin (α-SMA) and transforming growth factor β1 (TGF-β1) expression. Additionally, diabetic db/db mice displayed more terminal deoxynucleotidyl transferase-mediated nick-end labeling- (TUNEL-) positive nuclei and diabetes-induced ROS production in the kidneys, and these effects were attenuated by the treatment with GA, which activated adenosine monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling in the kidneys. In summary, in diabetic db/db mice, the effect of GA on DN involved, in part, the inhibition of ROS and the activation of AMPK/SIRT1/PGC-1α signaling in the kidneys. GA, therefore, shows therapeutic potential for preventing and treating DN.

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