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Multiple antioxidants improve cardiac complications and inhibit cardiac cell death in streptozotocin-induced diabetic rats.
PLoS One. 2013; 8(7):e67009.Plos

Abstract

Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. Since diabetic cardiomyopathy is now known to have a high prevalence in the asymptomatic diabetic patient, prevention at the earliest stage of development by existing molecules would be appropriate in order to prevent the progression of heart failure. In this study, we investigated the protective role of multiple antioxidants (MA), on cardiac dysfunction and cardiac cell apoptosis in streptozotocin (STZ)-induced diabetic rat. Diabetic cardiomyopathy in STZ-treated animals was characterized by declined systolic, diastolic myocardial performance, oxidative stress and apoptosis in cardiac cells. Diabetic rats on supplementation with MA showed decreased oxidative stress evaluated by the content of reduced levels of lipid per-oxidation and decreased activity of catalase with down-regulation of heme-oxygenase-1 mRNA. Supplementation with MA also resulted in a normalized lipid profile and decreased levels of pro-inflammatory transcription factor NF-kappaB as well as cytokines such as TNF-α, IFN-γ, TGF-β, and IL-10. MA was found to decrease the expression of ROS-generating enzymes like xanthine oxidase, monoamine oxidase-A along with 5-Lipoxygenase mRNA and/or protein expression. Further, left ventricular function, measured by a microtip pressure transducer, was re-established as evidenced by increase in ±dp/dtmax, heart rate, decreased blood pressure, systolic and diastolic pressure as well as decrease in the TUNEL positive cardiac cells with increased Bcl-2/Bax ratio. In addition, MA supplementation decreased cell death and activation of NF-kappaB in cardiac H9c2 cells. Based on our results, we conclude that MA supplementation significantly attenuated cardiac dysfunction in diabetic rats; hence MA supplementation may have important clinical implications in terms of prevention and management of diabetic cardiomyopathy.

Authors+Show Affiliations

National Centre for Cell Science, NCCS Complex, Ganeshkhind, Pune, India.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23843977

Citation

Kumar, Santosh, et al. "Multiple Antioxidants Improve Cardiac Complications and Inhibit Cardiac Cell Death in Streptozotocin-induced Diabetic Rats." PloS One, vol. 8, no. 7, 2013, pp. e67009.
Kumar S, Prasad S, Sitasawad SL. Multiple antioxidants improve cardiac complications and inhibit cardiac cell death in streptozotocin-induced diabetic rats. PLoS ONE. 2013;8(7):e67009.
Kumar, S., Prasad, S., & Sitasawad, S. L. (2013). Multiple antioxidants improve cardiac complications and inhibit cardiac cell death in streptozotocin-induced diabetic rats. PloS One, 8(7), e67009. https://doi.org/10.1371/journal.pone.0067009
Kumar S, Prasad S, Sitasawad SL. Multiple Antioxidants Improve Cardiac Complications and Inhibit Cardiac Cell Death in Streptozotocin-induced Diabetic Rats. PLoS ONE. 2013;8(7):e67009. PubMed PMID: 23843977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple antioxidants improve cardiac complications and inhibit cardiac cell death in streptozotocin-induced diabetic rats. AU - Kumar,Santosh, AU - Prasad,Sahdeo, AU - Sitasawad,Sandhya L, Y1 - 2013/07/02/ PY - 2012/08/12/received PY - 2013/05/17/accepted PY - 2013/7/12/entrez PY - 2013/7/12/pubmed PY - 2014/1/24/medline SP - e67009 EP - e67009 JF - PloS one JO - PLoS ONE VL - 8 IS - 7 N2 - Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. Since diabetic cardiomyopathy is now known to have a high prevalence in the asymptomatic diabetic patient, prevention at the earliest stage of development by existing molecules would be appropriate in order to prevent the progression of heart failure. In this study, we investigated the protective role of multiple antioxidants (MA), on cardiac dysfunction and cardiac cell apoptosis in streptozotocin (STZ)-induced diabetic rat. Diabetic cardiomyopathy in STZ-treated animals was characterized by declined systolic, diastolic myocardial performance, oxidative stress and apoptosis in cardiac cells. Diabetic rats on supplementation with MA showed decreased oxidative stress evaluated by the content of reduced levels of lipid per-oxidation and decreased activity of catalase with down-regulation of heme-oxygenase-1 mRNA. Supplementation with MA also resulted in a normalized lipid profile and decreased levels of pro-inflammatory transcription factor NF-kappaB as well as cytokines such as TNF-α, IFN-γ, TGF-β, and IL-10. MA was found to decrease the expression of ROS-generating enzymes like xanthine oxidase, monoamine oxidase-A along with 5-Lipoxygenase mRNA and/or protein expression. Further, left ventricular function, measured by a microtip pressure transducer, was re-established as evidenced by increase in ±dp/dtmax, heart rate, decreased blood pressure, systolic and diastolic pressure as well as decrease in the TUNEL positive cardiac cells with increased Bcl-2/Bax ratio. In addition, MA supplementation decreased cell death and activation of NF-kappaB in cardiac H9c2 cells. Based on our results, we conclude that MA supplementation significantly attenuated cardiac dysfunction in diabetic rats; hence MA supplementation may have important clinical implications in terms of prevention and management of diabetic cardiomyopathy. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23843977/Multiple_antioxidants_improve_cardiac_complications_and_inhibit_cardiac_cell_death_in_streptozotocin_induced_diabetic_rats_ L2 - http://dx.plos.org/10.1371/journal.pone.0067009 DB - PRIME DP - Unbound Medicine ER -