Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of oxidative stress

Aydemir-Koksoy, Aslihan; Bilginoglu, Ayca; Sarıahmetoğlu, Meltem; Schulz, Richard; Turan, Belma

doi:10.1016/j.jnutbio.2009.06.006

Cited by 40 publications

(19 citation statements)

References 51 publications

(87 reference statements)

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“…In our study, diabetes was induced in rats via the ip injection of STZ, which exerts preferential toxicity on the insulin-producing beta cells of the pancreas. DCM was confirmed in diabetic rats based on evidence of decreased LV systolic and diastolic myocardial performance, changes that are associated with substantial TUNEL-positive staining myocytes in cardiac tissue and are consistent with the results of previous studies [33,34] . Early responses of the heart to sustained hyperglycemia include metabolic disorders, subcellular defects, aberrant gene expression, and cell apoptosis [2] .…”

Section: Discussionsupporting

confidence: 88%

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

et al. 2015

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Aim: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Methods: Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg -1 ·d -1, po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. Results: DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Conclusion: Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

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Section: Discussionsupporting

confidence: 88%

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

et al. 2015

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“…Studies with natural antioxidants such as vitamin E, vitamin C, and a-lipoic acid have yielded promising results in animal models of diabetes, particularly when STZ is used to induce hyperglycemia (7,57). However, when investigated in humans, these antioxidants either alone or in combination have not shown consistent beneficial effects on serum metabolic parameters or the incidence of cardiovascular disease (65,108).…”

Section: Antioxidant Therapiesmentioning

confidence: 99%

The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

Schilling

2015

Antioxidants & Redox Signaling

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Significance: Diabetes is an important risk factor for the development of heart failure (HF). Given the increasing prevalence of diabetes in the population, strategies are needed to reduce the burden of HF in these patients. Recent Advances: Diabetes is associated with several pathologic findings in the heart including dysregulated metabolism, lipid accumulation, oxidative stress, and inflammation. Emerging evidence suggests that mitochondrial dysfunction may be a central mediator of these pathologic responses. The development of therapeutic approaches targeting mitochondrial biology holds promise for the management of HF in diabetic patients. Critical Issues: Despite significant data implicating mitochondrial pathology in diabetic cardiomyopathy, the optimal pharmacologic approach to improve mitochondrial function remains undefined. Future Directions: Detailed mechanistic studies coupled with more robust clinical phenotyping will be necessary to develop novel approaches to improve cardiac function in diabetes. Moreover, understanding the interplay between diabetes and other cardiac stressors (hypertension, ischemia, and valvular disease) will be of the utmost importance for clinical translation of scientific discoveries made in this field. Antioxid. Redox Signal. 22, 1515Signal. 22, -1526

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“…Low doses of doxycycline exert anti-inflammatory and antioxidant activity [23,24]. Hoyt et al [25] demonstrated that doxycycline inhibited NO production and also it protected the tissues against doxorubicin-induced oxidative stress and apoptosis in mouse [28,29]. Moreover, minocycline, a semisynthetic derivative of tetracycline having improved tissue adsorption, showed a marked protective effect against oxidative stress-induced injury depending on its antioxidant properties as a scavenger [23,24].…”

Section: Introductionmentioning

confidence: 99%

Doxycycline Ameliorates Vascular Endothelial and Contractile Dysfunction in the Thoracic Aorta of Diabetic Rats

2011

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Studies have shown that tetracycline class antibiotics exhibit an ameliorating action with its antioxidant property on increased oxidative stress in tissues, including heart. Since endothelial vascular dysfunction in diabetes is associated with increased oxidative stress and prevented with antioxidants, herein, we aimed to test a hypothesis whether a low-dose doxycycline treatment of diabetic rats for 4 weeks can ameliorate endothelial vascular dysfunction of thoracic aortas. Results of the present study shows that both direct and alpha receptor-mediated contractile responses as well as endothelium-dependent and endothelium-independent vasodilatory responses were preserved with low-dose doxycycline treatment (30 μmol/kg, daily; for 4 weeks) compared with untreated diabetic group. Furthermore, doxycycline treatment normalized increased lipid peroxidation and cellular glutathione level measured in plasma and prevented diabetes-induced impaired body weight gain without significant effect on high blood glucose level. Increased membrane protein level of caveolin-1, elevated ratio of PKC in particulate and cytosolic fraction, and increased protein level of cytosolic endothelin-1 in diabetic rats were also significantly prevented with doxycycline treatment. Moreover, diabetes-induced another type of oxidative stress markers in rats, matrix metalloproteinases, MMP-2, and MMP-9 were also normalized with doxycycline treatment in blood. Taken together, our data address that amelioration and/or prevention of vascular endothelial and contractile dysfunction by doxycycline is accompanied by a clear reduction in oxidative stress markers of diabetes, which provides evidence for doxycycline's potential antioxidant action as a therapeutic agent for amelioration and/or prevention of vascular disorders in diabetic subjects.

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Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of oxidative stress

Cited by 40 publications

References 51 publications

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

Doxycycline Ameliorates Vascular Endothelial and Contractile Dysfunction in the Thoracic Aorta of Diabetic Rats

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