Protective Effects of Methylsulfonylmethane on Hemodynamics and Oxidative Stress in Monocrotaline-Induced Pulmonary Hypertensive Rats

Mohammadi, Samaneh; Najafi, Moslem; Hamzeiy, Hossein; Maleki‐Dizaji, Nasrin; Pezeshkian, Masoud; Sadeghi-Bazargani, H; Darabi, Masoud; Mostafalou, Sara; Bohlooli, Shahab; Garjani, Alireza

doi:10.1155/2012/507278

Cited by 28 publications

(22 citation statements)

References 22 publications

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“…), and the right ventricular systolic pressure (RVSP) and heart rate (HR) were measured by PowerLab (AD Instruments) (Mohammadi et al. ). After the needle penetrated the intraventricular septum, the left ventricular systolic pressure (LVSP) was measured.…”

Section: Methodsmentioning

confidence: 99%

Hypoxia‐inducible factor‐1αdeletion in myeloid lineage attenuates hypoxia‐induced pulmonary hypertension

et al. 2019

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Hypoxemia is seen in patients with pulmonary hypertension and hypoxic pulmonary vasoconstriction worsens their clinical condition. However, vasoconstriction is not the only aspect through which hypoxia induces the progression to pulmonary hypertension. Hypoxia‐inducible factor‐1 α ( HIF ‐1 α ) is a transcription factor responding to hypoxic conditions by regulating hundreds of genes involved in angiogenesis, erythropoiesis, inflammation, and proliferation. We sought to determine the contribution of HIF ‐1 α in myeloid lineage cells to the pulmonary vascular response to chronic exposure to hypoxia. We generated myeloid‐specific HIF ‐1 α knockout (Mye HIF 1 KO ) mice by using Cre‐lox P system, and exposed them to hypoxic conditions for 3 weeks to induce pulmonary hypertension. Macrophages from Mye HIF 1 KO and control mice were used for western blotting, RT ‐ qPCR , chemotaxis assay, and ATP assay. Mye HIF 1 KO mice exposed to hypoxia for 3 weeks exhibited a significant reduction in the right ventricular systolic pressure accompanied by a decrease in the ratio of the right ventricular weight to left ventricular weight, muscularization of the small pulmonary arteries, and infiltration of macrophages into the lung and right ventricle compared with control mice. HIF ‐1 α ‐deficient peritoneal macrophages showed less migration toward monocyte chemoattractant protein‐1 and a decrease in intracellular ATP levels. These results indicate that HIF ‐1 α in macrophages contributes to the progression of pulmonary vascular remodeling and pulmonary hypertension induced by chronic exposure to hypoxic conditions. The inhibition of myeloid‐specific HIF ‐1 α may be a novel therapeutic strategy for the treatment of pulmonary hypertension.

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Section: Methodsmentioning

confidence: 99%

Hypoxia‐inducible factor‐1αdeletion in myeloid lineage attenuates hypoxia‐induced pulmonary hypertension

et al. 2019

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“…In recent years, oxidative stress has been indicated as a major contributor in the development of PH, suggesting that antioxidant therapy may be considered as a successful therapy against the disease [17][18][19][20][21][22][23]. Melatonin is a powerful antioxidant which can limit damage in cardiovascular disease [24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Melatonin as a preventive and curative therapy against pulmonary hypertension

Maarman

Blackhurst

Thienemann

et al. 2015

Journal of Pineal Research

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Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure, which leads to right ventricular (RV) hypertrophy and failure. The pathophysiological mechanisms of PH remain unclear but oxidative stress is believed to contribute to RV dysfunction. Melatonin is a powerful antioxidant and is cardioprotective against ischemia-reperfusion injury and hypertension. Therefore, we hypothesized that a chronic treatment with melatonin, given as a curative or preventive therapy, may confer cardiovascular benefits in PH. PH was induced in Long Evans rats (n ≥ 6 per group), with a single subcutaneous injection of monocrotaline (MCT, 80 mg/kg). Melatonin was given daily in the drinking water, with the treatment starting either on the day of the injection of MCT (dose testing: melatonin 75 ng/L and 6 mg/kg), 14 days after the injection of MCT (curative treatment: 6 mg/kg), or 5 days before the injection (preventive treatment: 6 mg/kg). The development of PH was assessed by measuring RV hypertrophy, RV function, cardiac interstitial fibrosis, and plasma oxidative stress. Compared with controls, MCT-treated rats displayed RV hypertrophy and dysfunction, increased interstitial fibrosis, and elevated plasma oxidative stress. A chronic melatonin treatment (75 ng/L or 6 mg/kg) reduced RV hypertrophy, improved RV function and reduced plasma oxidative stress. Curative and preventive treatment improved RV functional and plasma oxidative stress parameters and reduced cardiac interstitial fibrosis. Our data demonstrate that melatonin confers cardioprotection in this model of PH. As melatonin is an inexpensive and safe drug, we propose that clinical investigation of the effects of melatonin on RV function in patients with PH should be considered.

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“…Antioxidant enzyme activities in MCT-induced heart failure seem to differ with respect to the cellular type and compartment, and the results of various studies have been conflicting. Thus, Mohammadi et al (2012) found that levels of extracellular SOD and GSH-Px in MCT-treated rats were significantly decreased 4 weeks after treatment. Similar downregulation in antioxidant enzymes in MCT-induced heart failure was also found in soleus (oxidative and slow-twitching muscle) muscle tissue (Bertaglia et al 2011).…”

Section: Discussionmentioning

confidence: 87%

The influence of subchronic co-application of vitamins B6 and folic acid on cardiac oxidative stress and biochemical markers in monocrotaline-induced heart failure in male Wistar albino rats

Uzelac

Djukić

Mutavdzin

et al. 2020

Can. J. Physiol. Pharmacol.

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The aim of this study was to test the hypothesis that subchronic co-application of vitamins B6 and folic acid (FA) could affect heart failure (HF) induced by monocrotaline (MCT), with the modulation of oxidative stress parameters and cardiometabolic biomarkers. Biochemical and histomorphometric analyses were assessed in blank solution-exposed controls (C1 physiological saline 1 mL/kg, 1 day, n = 8; C2 physiological saline 1 mL/kg, 28 days, n = 8), MCT-induced HF (MCT 50 mg/kg, n = 8), B6+FA (vitamin B6 7 mg·kg–1·day–1, FA 5 mg·kg–1·day–1; n = 8), and MCT+B6+FA (MCT 50 mg/kg, vitamin B6 7 mg·kg–1·day–1, FA 5 mg·kg–1·day–1; n = 8) in male Wistar albino rats (body mass 160 g at the start). Superoxide dismutase and glutathione peroxidase activities, thiol-, carbonyl groups, and nitrotyrosine were determined in cardiac tissue. Echocardiography was performed to confirm MCT-induced HF. The right ventricular wall hypertrophy, accompanied with significant increase of troponin T and preserved renal and liver function, has been shown in MCT-induced HF. However, these effects were not related to antioxidant effects of vitamin B6 and FA, since several parameters of oxidative stress were more pronounced after treatment. In this study, co-application of vitamins B6 and FA did not attenuate hypertrophy of the right ventricle wall but aggravated oxidative stress, which is involved in HF pathogenesis.

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Protective Effects of Methylsulfonylmethane on Hemodynamics and Oxidative Stress in Monocrotaline-Induced Pulmonary Hypertensive Rats

Cited by 28 publications

References 22 publications

Hypoxia‐inducible factor‐1αdeletion in myeloid lineage attenuates hypoxia‐induced pulmonary hypertension

Hypoxia‐inducible factor‐1αdeletion in myeloid lineage attenuates hypoxia‐induced pulmonary hypertension

Melatonin as a preventive and curative therapy against pulmonary hypertension

The influence of subchronic co-application of vitamins B6 and folic acid on cardiac oxidative stress and biochemical markers in monocrotaline-induced heart failure in male Wistar albino rats

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