Combined metoprolol and ascorbic acid treatment prevents intrinsic damage to the heart during diabetic cardiomyopathy

Saran, Varun; Sharma, Vijay; Wambolt, Richard B.; Yuen, Violet G.; Allard, Michael F.; McNeill, John H.

doi:10.1139/cjpp-2014-0078

Cited by 7 publications

(6 citation statements)

References 35 publications

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“…Autoantibodies against the β1 receptor could be a predictor for left ventricular hypertrophy for T2DM patients with hypertension (50,51). Treatment with metoprolol could inhibit intrinsic damage to the heart during diabetic cardiomyopathy (52). Several studies indicated that use of beta-blockers, such as bisoprolol, did not aggravate glycemic control, lipid profile or albuminuria status in T2DM patients with SHF (53,54).…”

Section: Treatmentmentioning

confidence: 99%

“…Metoprolol and bisoprolol may inhibit the expression of c-fos through regulating the PKC-δ signaling pathways. Although there is little evidence of the effects of signal transduction pathways of beta-blockers on the expression of c-fos, one study showed that bisoprolol, especially at high doses, could increase the survival rate of hypertensive diastolic heart failure model of rats, at least partly through the alleviation of inflammatory changes (interleukin-1β, transforming growth factor-β1 and monocyte chemoattractant protein-1) and oxidative stress (reactive oxygen species production and nicotinamide adenine dinucleotide phosphate oxidase activity) (52). Moreover, isoproterenol (ISO)-induced heart failure could be inhibited by a Rho-associated protein kinase (ROCK) inhibitor, fasudil, which suppressed isoproterenol-induced JNK activation, translocation of ERK to the nucleus, and increased expression of c-fos and c-jun through RhoA/ROCK.…”

Section: Treatmentmentioning

confidence: 99%

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Metoprolol and bisoprolol ameliorate hypertrophy of neonatal rat cardiomyocytes induced by high glucose via the PKC/NF‑κB/c‑fos signaling pathway

Wei

Zhao

et al. 2019

Exp Ther Med

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Hyperglycemia caused by diabetes mellitus could increase the risk of diabetic cardiomyopathy. However, to the best of our knowledge, the underlying mechanism of this process is still not fully explored. Thus, developing ways to prevent hyperglycemia can be beneficial for diabetic patients. The present study was designed to investigate the influence of metoprolol and bisoprolol on the cardiomyocytic hypertrophy of neonatal rat cardiomyocytes. Cardiomyocytes were cultured in two types of media: One with low glucose levels and one with high glucose levels. Cardiomyocytes cultured in high glucose were further treated with the following: A protein kinase C (PKC) inhibitor, an NF-κB inhibitor, metoprolol or bisoprolol. The pulsatile frequency, cellular diameter and surface area of cardiomyocytes were measured. Protein content and [ 3 H]-leucine incorporation were determined, atrial natriuretic peptide (ANP), α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) mRNA levels were calculated by reverse transcription-quantitative PCR, while the expression and activation of PKC-α, PKC-β 2 , NF-κB, tumor necrosis factor-α (TNF-α), and c-fos were detected by western blotting. Metoprolol or bisoprolol were also used in combination with PKC inhibitor or NF-κB inhibitor to determine whether the hypertrophic response would be attenuated to a lower extent compared with metroprolol or bisoprolol alone. Cardiomyocytes cultured in high glucose presented increased pulsatile frequency, cellular diameter, surface area, and protein content and synthesis, higher expression of ANP and β-MHC, and lower α-MHC expression. High glucose levels also upregulated the expression and activation of PKC-α, PKC-β 2 , NF-κB, TNF-α and c-fos. Metoprolol and bisoprolol partly reversed the above changes, while combined use of metoprolol or bisoprolol with PKC inhibitor or NF-κB inhibitor further ameliorated the hypertrophic response mentioned above to lower levels compared with using metroprolol or bisoprolol alone. In conclusion, metoprolol and bisoprolol could prevent hypertrophy of cardiomyocytes cultured in high glucose by the inhibition of the total and phospho-PKC-α, which could further influence the PKC-α/NF-κB/c-fos signaling pathway.

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Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Metoprolol and bisoprolol ameliorate hypertrophy of neonatal rat cardiomyocytes induced by high glucose via the PKC/NF‑κB/c‑fos signaling pathway

Wei

Zhao

et al. 2019

Exp Ther Med

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“…Vitamin C has the ability of scavenging free radicals. This vitamin has cardioprotective properties, which were demonstrated to reduce oxidative damage in diabetic rats and during ischemia/reperfusion (I/R)-injury [12,13] . In some studies, vitamin C improved myocardial stunning and enhanced left ventricular function [14] .…”

Section: Discussionmentioning

confidence: 99%

The Effect of High-Dose Vitamin C on Biochemical Markers of Myocardial Injury in Coronary Artery Bypass Surgery

Emadi

Nemati

Ghorbani

et al. 2019

Braz J Cardiovasc Surg

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ObjectiveTo evaluate the effect of high-dose vitamin C on cardiac reperfusion injury and plasma levels of creatine kinase-muscle/brain (CK-MB), troponin I, and lactate dehydrogenase (LDH) in patients undergoing coronary artery bypass grafting (CABG).MethodsThis is a double-blind randomized clinical trial study. Fifty patients (50-80 years old) who had CABG surgery were selected. The intervention group received 5 g of intravenous vitamin C before anesthesia induction and 5 g of vitamin C in cardioplegic solution. The control group received the same amount of placebo (normal saline). Arterial blood samples were taken to determine the serum levels of CK-MB, troponin I, and LDH enzymes. Left ventricular ejection fraction was measured and hemodynamic parameters were recorded at intervals.ResultsHigh doses of vitamin C in the treatment group led to improvement of ventricular function (ejection fraction [EF]) and low Intensive Care Unit (ICU) stay. The cardiac enzymes level in the vitamin C group was lower than in the control group. These changes were not significant between the groups in different time intervals (anesthesia induction, end of bypass, 6 h after surgery, and 24 h after surgery) for CK-MB, LDH, and troponin I. Hemodynamic parameters, hematocrit, potassium, urinary output, blood transfusion, arrhythmia, and inotropic support showed no significant difference between the groups.ConclusionVitamin C has significantly improved the patients’ ventricular function (EF) 72 h after surgery and reduced the length of ICU stay. No significant changes in cardiac biomarkers, including CK-MB, troponin I, and LDH, were seen over time in each group.IRCT codeIRCT2016053019470N33

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“…Despite its capability to scavenge free radicals, vitamin C also promotes the differentiation of embryonic and pluripotent stem cells into cardiac myocytes [ 33 , 34 ]. Vitamin C has cardioprotective properties, which were demonstrated in rat models, where vitamin C reduced oxidative damage in diabetic rats [ 83 ] and during I/R-injury [ 84 ]. Vitamin C improved myocardial stunning and increased left ventricular function in some animal studies, however, other animal studies showed no effect of vitamin C and some only in combination with other antioxidants [ 49 ].…”

Section: Influence Of Vitamin C On Organ Systems In Cardiac Surgermentioning

confidence: 99%

Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients—Review and Pragmatic Approach

et al. 2018

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The pleiotropic biochemical and antioxidant functions of vitamin C have sparked recent interest in its application in intensive care. Vitamin C protects important organ systems (cardiovascular, neurologic and renal systems) during inflammation and oxidative stress. It also influences coagulation and inflammation; its application might prevent organ damage. The current evidence of vitamin C’s effect on pathophysiological reactions during various acute stress events (such as sepsis, shock, trauma, burn and ischemia-reperfusion injury) questions whether the application of vitamin C might be especially beneficial for cardiac surgery patients who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of vitamin C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between vitamin C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence on the administration of vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage, and appropriate application strategy.

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Combined metoprolol and ascorbic acid treatment prevents intrinsic damage to the heart during diabetic cardiomyopathy

Cited by 7 publications

References 35 publications

Metoprolol and bisoprolol ameliorate hypertrophy of neonatal rat cardiomyocytes induced by high glucose via the PKC/NF‑κB/c‑fos signaling pathway

Metoprolol and bisoprolol ameliorate hypertrophy of neonatal rat cardiomyocytes induced by high glucose via the PKC/NF‑κB/c‑fos signaling pathway

The Effect of High-Dose Vitamin C on Biochemical Markers of Myocardial Injury in Coronary Artery Bypass Surgery

Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients—Review and Pragmatic Approach

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