Effect of angiotensin-converting enzyme inhibitor on cardiac fibrosis and oxidative stress status in lipopolysaccharide-induced inflammation model in rats

Abareshi, Azam; Norouzi, Fatemeh; Asgharzadeh, Fereshteh; Beheshti, Farimah; Hosseini, Mahmoud; Farzadnia, Mehdi; Khazaei, Majid

doi:10.4103/ijpvm.ijpvm_322_16

Cited by 25 publications

(16 citation statements)

References 26 publications

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“…The inhibition of ACE reduces angiotensin II which will cause fibrotic effects through the AT1 receptor, and also enhance the reduction effect by increasing bradykinin; this would be the advantage of ACEIs over AT-1 receptor blockers on reducing cardiac fibrosis. A study from Abareshi et al (74) showed that ACEIs reduce inflammation and fibrosis through the reduction of IL-6 and TNF-α. Deijanera et al (75) demonstrated the ACEIs have an effect on reducing TGF-β1, TGF-β2, and Th2 cytokines.…”

Section: The Role Of Aceis In Cardiac Fibrosis In Rhdmentioning

confidence: 99%

Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2

Ambari

Setianto

Santoso

et al. 2020

Front. Cardiovasc. Med.

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Rheumatic heart disease (RHD) is common in developing countries and poses a big medical challenge and burden. The pathogenesis of RHD is influenced by the triad of host, agent, and environment. Autoantigens generated from Group A Streptococcus (GAS) infection are captured by the resident dendritic cells (DCs) in the heart's valvular endothelium. DCs differentiate into antigen presenting cells (APC) in the valve interstices. APC induces activation of autoreactive T cells, which triggers inflammation and tissue fibrosis. Cardiac fibrosis is promoted through the activation of Mitogen activated protein kinases (MAPKs) and its downstream signaling, including its interaction with transforming growth factor-β (TGF-β) and Smad proteins. TGF-β-induced phosphorylation of Smad2 complexes with Smad3 and Smad4, and translocates into the nucleus. Angiotensin II enhances the migration, maturation, and presentation of DC. In RHD, Angiotensin II induces fibrosis via the stimulation of TGF-β, which further increases the binding of IL-33 to sST2 but not ST2L, resulting in the upregulation of Angiotensin II and progression of cardiac fibrosis. This cascade of inflammation and valvular fibrosis causes calcification and stiffening of the heart valves in RHD. Angiotensin converting enzyme inhibitors (ACEIs) inhibit Angiotensin II production, which in turn decreases TGF-β expression and the onset of overt inflammatory response. This condition leads to a reduction in the sST2 as the decoy receptor to "steal" IL-33, and IL-33 binds to ST2L and results in cardioprotection against cardiac fibrosis in the pathogenesis of RHD.

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Section: The Role Of Aceis In Cardiac Fibrosis In Rhdmentioning

confidence: 99%

Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2

Ambari

Setianto

Santoso

et al. 2020

Front. Cardiovasc. Med.

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“…13 We also previously showed that ACE inhibitors including captopril had some anti-oxidant effects. 30,31 Thus, the ability of captopril to reverse PTZ-induced seizures which was observed in the current study may at least in part be due to enhancement of antioxidant defense system and attenuation of oxidative stress in the brain. 32 This action might be resulted from its ability to overcome the pro-oxidant effects of PTZ-induced seizures, through increase in antioxidant defense systems including GSH, SOD and CAT and a decrease in MDA and nitrite levels in the brain.…”

Section: Discussionmentioning

confidence: 63%

Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice<br />

et al. 2019

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IntroductionEpileptic seizures are considered as a sever abnormal activity of neurons in specific areas of brain such as temporal lobe. 1 This abnormal activity of neurons can be followed by brain oxidative stress and disturbance of cognitive behaviors when they take place repeatedly. 2 In the epileptic seizure models, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase have been also shown to protect the brain of rats against oxidative damage. 3 In large number of animal studies, pentylenetetrazole (PTZ) has been repeatedly administered for induction an epilepsy model. 1 It has been ducumented that PTZstimulated seizures was accompanied with motor activity impairment, learning and memory dysfunction, axiety and increased level of hippocampal inflammatory cytokines in rats. 4 In addition, seizures followed by PTZ administration have been propounded as an important cause of oxidative status imbalance in some brain areas including hippocampus. 5 For example, PTZ infusion associated with the sever stimulation of N-Methyl-Daspartate (NMDA) receptors has been shown to elevate the level of free radicals such as nitric oxide (NO) and peroxynitrite in the brain of rats. 6 On the other hand, the antioxidant properties of angiotensin-converting enzyme (ACE) inhibitors have been accepted. 7 Captopril as a known ACE inhibitor scavenges free radicals in various tissues. 8 Captopril has been demonstrated to reinforce enzymatic and nonenzymatic defense in different tissues. 9 Scientific evidence has indicated that captopril and valsartan (a specific AT1 receptor inhibitor) attenuate A B S T R A C TBackground: Frequent seizure is followed by overproduction of free radicals and brain oxidative stress. Renin angiotensin system (RAS) has some effects on central nervous system. We designed this research to challenge the effect of captopril as an angiotensin converting enzyme (ACE) inhibitor against brain oxidative stress in pentylenetetrazole (PTZ) -induced seizures in mice. Methods: The groups were including (1) Control (saline); (2) PTZ (100 mg/kg, i.p.), (3-5) PTZ-captopril (Capto) that received three doses of Capto 10, 50 and 100 mg/kg 30 min before PTZ injection. Latency time in the onset minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) were recorded. The level of malondialdehyde (MDA) and total thiol, as well as superoxide dismutase (SOD) and catalase (CAT) activity in the hippocampus and cortex were measured. Results: All doses of captopril postponed the onset of MCS and GTCS. Accumulation of MDA in the brain tissues of PTZ group was higher than control group, while total thiol content and CAT activity were lower. Pretreatment with captopril (100 mg/kg) diminished MDA concentration compared with PTZ group. Captopril (50 and 100 mg/kg) also increased the level of total thiol groups versus PTZ group. Captopril injection (50 and 100 mg/kg) elevated the activity of SOD and CAT in the brain tissues. In addition captopril administration diminished mortality rat...

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“…CAP, an angiotensin-converting enzyme inhibitor commonly used in clinic, has been reported that is effective at ameliorating MF ( Abareshi et al, 2017 ; Wang et al, 2019c ), so it was used as a positive control in this study. According to our present results, 8-Gin produced an anti-fibrotic effect similar to that of CAP, but the therapeutic effect of CAP was stronger than 8-Gin.…”

Section: Discussionmentioning

confidence: 99%

8-Gingerol Ameliorates Myocardial Fibrosis by Attenuating Reactive Oxygen Species, Apoptosis, and Autophagy via the PI3K/Akt/mTOR Signaling Pathway

Xue

Liu

et al. 2021

Front. Pharmacol.

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8-gingerol (8-Gin) is the series of phenolic substance that is extracted from ginger. Although many studies have revealed that 8-Gin has multiple pharmacological properties, the possible underlying mechanisms of 8-Gin against myocardial fibrosis (MF) remains unclear. The study examined the exact role and potential mechanisms of 8-Gin against isoproterenol (ISO)-induced MF. Male mice were intraperitoneally injected with 8-Gin (10 and 20 mg/kg/d) and concurrently subcutaneously injected with ISO (10 mg/kg/d) for 2 weeks. Electrocardiography, pathological heart morphology, myocardial enzymes, reactive oxygen species (ROS) generation, degree of apoptosis, and autophagy pathway-related proteins were measured. Our study observed 8-Gin significantly reduced J-point elevation and heart rate. Besides, 8-Gin caused a marked decrease in cardiac weight index and left ventricle weight index, serum levels of creatine kinase and lactate dehydrogenase (CK and LDH, respectively), ROS generation, and attenuated ISO-induced pathological heart damage. Moreover, treatment with 8-Gin resulted in a marked decrease in the levels of collagen types I and III and TGF-β in the heart tissue. Our results showed 8-Gin exposure significantly suppressed ISO-induced autophagosome formation. 8-Gin also could lead to down-regulation of the activities of matrix metalloproteinases-9 (MMP-9), Caspase-9, and Bax protein, up-regulation of the activity of Bcl-2 protein, and alleviation of cardiomyocyte apoptosis. Furthermore, 8-Gin produced an obvious increase in the expressions of the PI3K/Akt/mTOR signaling pathway-related proteins. Our data showed that 8-Gin exerted cardioprotective effects on ISO-induced MF, which possibly occurred in connection with inhibition of ROS generation, apoptosis, and autophagy via modulation of the PI3K/Akt/mTOR signaling pathway.

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Effect of angiotensin-converting enzyme inhibitor on cardiac fibrosis and oxidative stress status in lipopolysaccharide-induced inflammation model in rats

Cited by 25 publications

References 26 publications

Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2

Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2

Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice<br />

8-Gingerol Ameliorates Myocardial Fibrosis by Attenuating Reactive Oxygen Species, Apoptosis, and Autophagy via the PI3K/Akt/mTOR Signaling Pathway

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