Azilsartan Improves Glycemic Status and Reduces Kidney Damage in Zucker Diabetic Fatty Rats

Khan, Abdul Hye; Neckář, Jan; Haines, Jasmine; Imig, John D.

doi:10.1093/ajh/hpu016

Cited by 20 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In several earlier studies, others and we reported such renal oxidative stress and inflammation along with marked kidney injury in ZDF rats [19,50]. Consistent with these earlier findings, there are marked elevation in urinary excretion of MCP-1, renal infiltration of macrophages, and the kidney levels of MDA is elevated in the ZDF rats [19,50].…”

Section: Discussionsupporting

confidence: 89%

A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat

Khan

Hwang

Sharma

et al. 2016

Prostaglandins & Other Lipid Mediators

View full text Add to dashboard Cite

Cyclooxygenase (COX) and soluble epoxide hydrolase (sEH) inhibitors have therapeutic potential. The present study investigated efficacy of a novel dual acting COX-2/sEH inhibitor, PTUPB in type 2 diabetic Zucker Diabetic Fatty (ZDF) rats. Male ZDF rats were treated with vehicle or PTUPB (10 mg/kg/d, i.p.) for 8 weeks. At the end of the 8-week experimental period, ZDF rats were diabetic (fasting blood glucose, 287±45 mg/dL) compared to Zucker Diabetic Lean rats (ZDL, 99±6 mg/dL), and PTUPB treatment improved glycemic status in ZDF rats (146±6 mg/dL). Kidney injury was evident in ZDF compared to ZDL rats with elevated albuminurea (44±4 vs 4±2 mg/d) and nephrinurea (496±127 vs 16±4 μg/d). Marked renal fibrosis, tubular cast formation and glomerular injury were also present in ZDF compared to ZDL rats. In ZDF rats, PTUPB treatment reduced kidney injury parameters by 30–80% compared to vehicle. The ZDF rats also demonstrated increased inflammation and oxidative stress with elevated levels of urinary monocyte chemoattractant protein-1 excretion (862±300 vs 319±75 ng/d), renal macrophage infiltration (53±2 vs 37±4 /mm2) and kidney malondialdehyde/protein ratio (10±1 vs 5±1 μmol/mg). PTUPB treatment decreased these inflammatory and oxidative stress markers in the kidney of ZDF rats by 25–57%. These data demonstrate protective actions of a novel dual acting COX-2/sEH inhibitor on the metabolic abnormalities and kidney function in ZDF rat model of type 2 diabetes.

show abstract

Section: Discussionsupporting

confidence: 89%

A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat

Khan

Hwang

Sharma

et al. 2016

Prostaglandins & Other Lipid Mediators

View full text Add to dashboard Cite

show abstract

“…Apart from its main applications, azilsartan was revealed to exert beneficial effects in animal models of myocardial infarction [20]. Meanwhile, azilsartan was able to ameliorate metabolic syndrome and kidney damage in rats with type 2 diabetes [21]. In addition, anti-inflammatory actions of oral azilsartan treatment was also observed in an experimental model of oral mucositis [22].…”

Section: Discussionmentioning

confidence: 99%

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson’s disease

Gao

Jiang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinsons disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased. Furthermore, we provided in vivo evidence that Ang II directly elicited apoptosis of dopaminergic neurons via activation of AT1R in the SN of rats. More importantly, we showed for the first time that oral administration of azilsartan, a newly developed AT1R blocker approved by the U.S. Food and Drug Administration for hypertension treatment, rescued the apoptosis of dopaminergic neurons and relieved the characteristic parkinsonian symptoms in PD rats. These results support the application of AT1R blockers in PD therapy, and strengthen the notion that many therapeutic agents may possess pleiotropic action in addition to their main applications.

show abstract

“…A possible role of Azilsartan in metabolic syndrome has been suggested in a study in obese rats demonstrating its insulin sensitizing effect. 12,13 Beneficial effects like vasculoprotection, left ventricular remodelling has also been demonstrated in various animal studies. [14][15][16] Azilsartan is also claimed to have renoprotective effects in terms of reducing proteinuria, albuminuria and glomerular injury.…”

Section: Experimental Evidencesmentioning

confidence: 96%

Azilsartan: the novel ARB with unique mechanism of action

Hiremath

Hajare

Chinchansur

et al. 2017

Int J Basic Clin Pharmacol

View full text Add to dashboard Cite

Hypertension is attributed to be one of the major risk factors in the pathophysiology of ischemic heart disease, stroke, heart failure and renal dysfunction. Angiotensin receptor blockers (ARBs) are one of the first line drugs recommended for clinical use in hypertension by JNC 8. Azilsartan is the recent addition to this family of ARBs and is perceived as one of the potent antihypertensive drugs today. Azilsartan was developed by replacing the tetrazole ring in candesartan with a 5 member oxo-oxadiazole ring. In India Azisartan was recently approved by DCGI in December 2016 for use in hypertension. In various randomized, double blind clinical studies Azilsartan was found to be to be superior in terms of clinical efficacy over other ARBs like Candesartan, Olmesartan and Valsartan and angiotensin converting enzyme inhibitor like Ramipril. In terms of safety profile Azilsartan appears to be equivalent to the currently available ARBs. Azilsartan due to its superior efficacy and comparative safety profile appear to be a new addition to the armamentarium in the treatment of hypertension.

show abstract

Azilsartan Improves Glycemic Status and Reduces Kidney Damage in Zucker Diabetic Fatty Rats

Abstract: Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action.

Cited by 20 publications

References 41 publications

A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat

A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson’s disease

Azilsartan: the novel ARB with unique mechanism of action

Contact Info

Product

Resources

About