DPP-4 Inhibitor and Estrogen Share Similar Efficacy Against Cardiac Ischemic-Reperfusion Injury in Obese-Insulin Resistant and Estrogen-Deprived Female Rats

Sivasinprasasn, Sivaporn; Tanajak, Pongpan; Pongkan, Wanpitak; Pratchayasakul, Wasana; Chattipakorn, Nipon

doi:10.1038/srep44306

Cited by 18 publications

(23 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Estrogen treatment was prepared using estradiol powder (Sigma-Aldrich Co.) dissolved in ethanol and then mixed with sesame oil (Sigma-Aldrich Co.). The regular dose of estradiol used in this study was previously demonstrated to improve cardiometabolic status in ovariectomized female rats (Sivasinprasasn et al 2016(Sivasinprasasn et al , 2017. The NAC solution was prepared by mixing NAC powder with normal saline (NSS) using the concentration of NAC 40 mg per 200 μL of NSS.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…An echocardiograph (SONOS4500, Philips with S12 probe, Hewlett Packard) was used for collecting the data. Signals from pulsed-wave Doppler and M-mode echocardiography at the papillary muscle level were recorded (Sivasinprasasn et al 2017).…”

Section: Echocardiography Protocolmentioning

confidence: 99%

“…The time to 1st VT/VF onset and the mortality rate were recorded. Arrhythmia score was evaluated (Sivasinprasasn et al 2017).…”

Section: Cardiac Ischemia/reperfusion (I/r) Protocolmentioning

confidence: 99%

“…The myocardial area without blue-dyed color was defined as the area at risk (AAR). The viable tissue was in red, and the area which exhibited neither blue nor red was identified as the myocardial infarction (Sivasinprasasn et al 2017). Myocardial infarction was determined using the Image tool software version 3.0.…”

Section: Determination Of Myocardial Infarct Sizementioning

confidence: 99%

“…Also, endogenous estrogen deficiency resulted in more severe cardiac tissue damage and left ventricular dysfunction after myocardial ischemia and reperfusion (I/R) (Zhai et al 2000). In estrogen-deprived animals undergoing cardiac I/R, cardiac mitochondria were more damaged leading to impaired mitochondrial function (Sivasinprasasn et al 2017). Furthermore, women also have an increased prevalence of metabolic syndrome including dyslipidemia, insulin resistance, visceral fat deposition and central obesity following menopause.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury

Sivasinprasasn

Palee

Chattipakorn

et al. 2019

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Myocardial damage and mitochondrial dysfunction caused by cardiac ischemia-reperfusion (I/R) injury are intensified by endogenous estrogen deprivation. Although N-acetylcysteine (NAC) exerted cardioprotective effects, its benefits when used in combination with hormone therapy are unknown. We tested the hypothesis that a combination of NAC with low-dose estrogen improves cardiometabolic function and protects cardiac mitochondria against I/R injury, to a similar extent to regular-dose estrogen treatment, in estrogen-deprived rats. Female Wistar rats had a bilateral ovariectomy (OVX) or sham operation. Twelve weeks after the operation, OVX rats were treated with regular-dose estrogen (E; 50 µg/kg/day), low-dose estrogen (e; 25 µg/kg/day), NAC (N; 100 mg/kg/day) or combined low-dose estradiol with NAC (eN) for 4 weeks (n = 6/group). Metabolic parameters, echocardiography, heart rate variability and then cardiac I/R protocol involving 30-min coronary artery ligation, followed by 120-min reperfusion, were performed. OVX rats had increased body weight, visceral fat, fasting plasma glucose, HOMA-IR index, triglycerides, cholesterol and LDL levels (P < 0.05 vs sham). Only OVX-E and OVX-eN had a similarly improved HOMA-IR index. LVEF was increased in all treatment groups, but HRV was restored only by OVX-E and OVX-eN. After I/R, myocardial infarct size was decreased in both OVX-E and OVX-eN groups. OVX-E and OVX-eN rats similarly had a reduced mitochondrial ROS level and increased mitochondrial membrane potential in the ischemic myocardium. In conclusion, combined NAC with low-dose estrogen and regular-dose estrogen therapy similarly improve cardiometabolic function, prevent cardiac mitochondrial dysfunction and reduces the infarct size in estrogen-deprived rats with cardiac I/R injury.

show abstract

Section: Experimental Protocolmentioning

confidence: 99%

Section: Echocardiography Protocolmentioning

confidence: 99%

“…The time to 1st VT/VF onset and the mortality rate were recorded. Arrhythmia score was evaluated (Sivasinprasasn et al 2017).…”

Section: Cardiac Ischemia/reperfusion (I/r) Protocolmentioning

confidence: 99%

Section: Determination Of Myocardial Infarct Sizementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury

Sivasinprasasn

Palee

Chattipakorn

et al. 2019

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

Estrogen deprivation aggravates intracellular calcium dyshomeostasis in the heart of obese‐insulin resistant rats

Palee

Minta

Mantor

et al. 2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

The incidence of cardiovascular disease and metabolic syndrome increases after the onset of menopause, giving evidence for the vital role of estrogen. Intracellular calcium [Ca 2+ ]i regulation plays an important role in the maintenance of left ventricular (LV) contractile function. Although either estrogen deprivation or obesity has been shown to strongly affect the metabolic status and LV function, the effects of estrogen deprivation on the cardiometabolic status and cardiac [Ca 2+ ]i regulation in the obese-insulin resistant condition have never been investigated. Our hypothesis was that estrogen deprivation aggravates LV dysfunction through the increased impairment of [Ca 2+ ]i homeostasis in obese-insulin resistant rats. Female rats were fed on either a high-fat (HFD, 59.28% fat) or normal (ND, 19.77% fat) diet for 13 weeks. Then, rats were divided into sham (HFS and NDS) operated or ovariectomized (HFO and NDO) groups. Six weeks after surgery, metabolic status, LV function and incidence of [Ca 2+ ]i transients were determined. NDO, HFS, and HFO rats had evidence of obese-insulin resistance indicated by increased body weight with hyperinsulinemia and euglycemia. Although NDO, HFS, and HFO rats had markedly reduced %LV fractional shortening, E/A ratio and decreased [Ca 2+ ]i transient amplitude and decay rate, HFO rats had the most severe impairments. These findings indicate that estrogen deprivation had a strong impact on abnormal LV function through [Ca 2+ ]i regulation. In addition, evidence was found that in obese-insulin resistant rats, estrogen deprivation severely aggravates LV dysfunction via increased impairment of [Ca 2+ ]i homeostasis.

show abstract

Neuroprotective effect of vildagliptin against cerebral ischemia in rats

El-Marasy

Abdel-Rahman

Abd‐Elsalam

2018

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Stroke is the leading cause of death worldwide. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of anti-diabetic drugs for treatment of type-2 diabetes mellitus. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent of its anti-diabetic properties in non-diabetic rats subjected to cerebral ischemia. Anesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24 h following reperfusion. Forty-eight hours following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological deficit score, locomotor activity, and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphoryated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted a neuroprotective effect in a dose-dependent manner as shown in the attenuation of the infarct area, neuronal cell loss, and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, its antioxidant property, activation of the PI3K/AKT/mTOR pathway, and its anti-apoptotic effect.

show abstract

DPP-4 Inhibitor and Estrogen Share Similar Efficacy Against Cardiac Ischemic-Reperfusion Injury in Obese-Insulin Resistant and Estrogen-Deprived Female Rats

Cited by 18 publications

References 60 publications

N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury

N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury

Estrogen deprivation aggravates intracellular calcium dyshomeostasis in the heart of obese‐insulin resistant rats

Neuroprotective effect of vildagliptin against cerebral ischemia in rats

Contact Info

Product

Resources

About