Cardioprotective effects of magnesium valproate in type 2 diabetes mellitus

Patel, Bhoomika M.; Raghunathan, Suchi; Porwal, Urvashi

doi:10.1016/j.ejphar.2014.01.063

Cited by 37 publications

(19 citation statements)

References 28 publications

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“…More importantly, VPA is also an established drug for the long-term therapy of epilepsy because of its HDAC inhibition activity (45). Up to date, a number of studies have shown that VPA plays an important role in the prevention of multiple cardiac pathological changes induced by different stimuli (36, 46–48), including type 2 diabetes (49). …”

Section: Discussionmentioning

confidence: 99%

Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway

et al. 2017

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Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination. HDAC3 activity was significantly increased in the heart of diabetic mice. Administration of RGFP966 significantly prevented DCM, as evidenced by improved diabetes-induced cardiac dysfunction, hypertrophy and fibrosis, along with diminished cardiac oxidative stress, inflammation, and insulin resistance, not only in the mice sacrificed immediately or 3 months later following the three-month treatment. Furthermore, phosphorylated extracellular signal-regulated kinases (ERK) 1/2, a well-known initiator of cardiac hypertrophy, was significantly increased, while dual specificity phosphatase 5 (DUSP5), an ERK1/2 nuclear phosphatase, was substantially decreased in diabetic hearts. Both of these changes were prevented by RGFP966. Chromatin immunoprecipitation assay showed that HDAC3 inhibition elevated histone H3 acetylation on the DUSP5 gene promoter at both two-time points. These findings suggest that diabetes-activated HDAC3 inhibits DUSP5 expression through deacetylating histone H3 on the primer region of DUSP5 gene, leading to the derepression of ERK1/2 and the initiation of DCM. This study indicates the potential application of HDAC3 inhibitor for the prevention of DCM.

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Section: Discussionmentioning

confidence: 99%

Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway

et al. 2017

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“…DCM is a major complication of DM, and it contributes to the mortality of diabetes due to its ability to result in cardiac failure. Pre-existing cardiovascular risk factors, such as coronary artery disease and hypertension, are not necessary for the development of DCM; pathogenesis can occur independently of these factors (14). The pathogenic mechanisms of DCM are relatively complex; they include insulin resistance and cardiomyocyte hypertrophy, an increased apoptotic rate of cardiomyocytes, myocardial fibrosis and remodeling of myofibrils, cardiovascular autonomic neuropathy and calcium ion overloading in myocardial cells (15).…”

Section: Discussionmentioning

confidence: 99%

Troxerutin protects against diabetic cardiomyopathy through NF-κB/AKT/IRS1 in a rat model of type 2 diabetes

Zheng

2017

Molecular Medicine Reports

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Troxerutin is a bioflavonoid, which can be used to treat venous disorders, thrombosis and cerebrovascular diseases. Recent studies have demonstrated that it may also be used to prevent edemas. However, it is not known whether troxerutin protects against the cardiomyopathic complications of diabetes. In the present study, a rat model of type 2 diabetes was used to investigate the potential for troxerutin to protect against diabetic cardiomyopathy, through changes to nuclear factor-κB (NF-κB) expression. Troxerutin administration significantly reduced heart rate, blood pressure, blood glucose and plasma triglyceride levels across all measured time points. Furthermore, troxerutin significantly reduced reactive oxygen species levels, NF-κB protein expression, and suppressed the phosphorylated forms of AKT, insulin receptor substrate 1 (IRS1) and c-Jun N-terminal kinase (JNK). These results suggested that troxerutin protects against cardiomyopathy via alterations in NF-κB, AKT and IRS1 signaling, in a rat model of type 2 diabetes.

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“…In this study, a significant elevation in the level of glycosylated haemoglobin was observed in the sera of T2D rats. Increased CK and LDH contents in the sera are primary indication of cellular damage [55]. These membrane bound enzymes come into the blood during cellular injury.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, a significantly high ROS production was observed in cardiac tissues of T2D rats. An enhanced generation of ROS would result in the increases in lipid peroxidation, protein carbonylation with concomitant depletion of endogenous antioxidant molecules [55,56]. Therefore, it would be concluded that myocardial tissues experienced to redox challenge/oxidative stress during DM.…”

Section: Discussionmentioning

confidence: 99%

Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) Attenuates Type 2 Diabetes and Its Associated Cardiomyopathy

et al. 2016

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BackgroundSansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal literature in India. Therefore, present experiments were carried out to explore the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR) against experimentally induced type 2 diabetes mellitus (T2DM) and its associated cardiomyopathy in Wistar rats.MethodsSR was chemically characterized by GC-MS analysis. Antidiabetic activity of SR (50 and 100 mg/kg, orally) was measured in high fat diets (ad libitum) + low-single dose of streptozotocin (35 mg/kg, intraperitoneal) induced type 2 diabetic (T2D) rat. Fasting blood glucose level was measured at specific intermissions. Serum biochemical and inflammatory markers were estimated after sacrificing the animals. Besides, myocardial redox status, expressions of signal proteins (NF-κB and PKCs), histological and ultrastructural studies of heart were performed in the controls and SR treated T2D rats.ResultsPhytochemical screening of the crude extract revealed the presence of phenolic compounds, sugar alcohols, sterols, amino acids, saturated fatty acids within SR. T2D rats exhibited significantly (p < 0.01) higher fasting blood glucose level with respect to control. Alteration in serum lipid profile (p < 0.01) and increased levels of lactate dehydrogenase (p < 0.01) and creatine kinase (p < 0.01) in the sera revealed the occurrence of hyperlipidemia and cell destruction in T2D rats. T2DM caused significant (p < 0.05–0.01) alteration in the biochemical markers in the sera. T2DM altered the redox status (p < 0.05–0.01), decreased (p < 0.01) the intracellular NAD and ATP concentrations in the myocardial tissues of experimental rats. While investigating the molecular mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats also exhibited an up-regulation in nuclear NF-κB (p65) in the cardiac tissues. So, oral administration of SR (50 and 500 mg/kg) could reduce hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological and ultra-structural studies of cardiac tissues supported the protective characteristics of SR.ConclusionsFrom the present findings it can be concluded that, SR could offer protection against T2DM and its associated cardio-toxicity via multiple mechanisms viz. hypoglycemic, antioxidant and anti-inflammatory actions.

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Cardioprotective effects of magnesium valproate in type 2 diabetes mellitus

Cited by 37 publications

References 28 publications

Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway

Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway

Troxerutin protects against diabetic cardiomyopathy through NF-κB/AKT/IRS1 in a rat model of type 2 diabetes

Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) Attenuates Type 2 Diabetes and Its Associated Cardiomyopathy

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