Quantification of DNA Damage in Different Tissues in Rats with Heart Failure

Background Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.

[1]  A. Sonza,et al.  Respiratory muscle training decreases diaphragm DNA damage in rats with heart failure. , 2018, Canadian journal of physiology and pharmacology.

[2]  M. Emdin,et al.  Targeting Mitochondrial Dysfunction in Chronic Heart Failure: Current Evidence and Potential Approaches. , 2016, Current pharmaceutical design.

[3]  Katarzyna Pietraszek-Gremplewicz,et al.  The role of oxidative stress in skeletal muscle injury and regeneration: focus on antioxidant enzymes , 2015, Journal of Muscle Research and Cell Motility.

[4]  H. Iwao,et al.  Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction. , 2015, International journal of cardiology.

[5]  Romain Chayot,et al.  More efficient repair of DNA double-strand breaks in skeletal muscle stem cells compared to their committed progeny. , 2014, Stem cell research.

[6]  R. Nunes,et al.  Resistance Training Improves Hemodynamic Function, Collagen Deposition and Inflammatory Profiles: Experimental Model of Heart Failure , 2014, PloS one.

[7]  P. Scheffer,et al.  8-Hydroxy-2′-Deoxyguanosine and Cardiovascular Disease: a Systematic Review , 2014, Current Atherosclerosis Reports.

[8]  A. Ahmed,et al.  Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats. , 2014, Life sciences.

[9]  C. Scavone,et al.  NADPH oxidase hyperactivity induces plantaris atrophy in heart failure rats. , 2014, International journal of cardiology.

[10]  Andrew R Collins,et al.  Measuring oxidative damage to DNA and its repair with the comet assay. , 2014, Biochimica et biophysica acta.

[11]  C. Hoppel,et al.  Mitochondrial dysfunction in heart failure , 2013, Heart Failure Reviews.

[12]  P. Schulze,et al.  Metabolic and structural impairment of skeletal muscle in heart failure , 2013, Heart Failure Reviews.

[13]  C. Maack,et al.  Myocardial energetics in heart failure , 2013, Basic Research in Cardiology.

[14]  I. Conboy,et al.  Regenerative Capacity of Old Muscle Stem Cells Declines without Significant Accumulation of DNA Damage , 2013, PloS one.

[15]  L. Xavier,et al.  Low-level laser therapy improves the inflammatory profile of rats with heart failure , 2013, Lasers in Medical Science.

[16]  Damien M. Callahan,et al.  Skeletal muscle protein metabolism in human heart failure , 2013, Current opinion in clinical nutrition and metabolic care.

[17]  D. Delgado,et al.  Experimental biomarkers in heart failure: an update , 2012, Expert review of cardiovascular therapy.

[18]  L. A. Bonet,et al.  ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 , 2012, Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir.

[19]  L. Xavier,et al.  Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure. , 2011, Journal of applied physiology.

[20]  A. Criollo,et al.  Cardiomyocyte death: mechanisms and translational implications , 2011, Cell Death and Disease.

[21]  S. Paiva,et al.  Critical infarct size to induce ventricular remodeling, cardiac dysfunction and heart failure in rats. , 2011, International journal of cardiology.

[22]  A. Georgakilas,et al.  Role of oxidative stress and DNA damage in human carcinogenesis. , 2011, Mutation research.

[23]  M. Irigoyen,et al.  MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats. , 2011, Physiological genomics.

[24]  M. Yano,et al.  Urinary 8‐hydroxy‐2′‐deoxyguanosine reflects symptomatic status and severity of systolic dysfunction in patients with chronic heart failure , 2011, European journal of heart failure.

[25]  R. Kitsis,et al.  Cell death in the pathogenesis of heart disease: mechanisms and significance. , 2010, Annual review of physiology.

[26]  C. Padovani,et al.  Echocardiographic detection of congestive heart failure in postinfarction rats. , 2009, Journal of applied physiology.

[27]  C. Schneider,et al.  ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: application of natriuretic peptides. , 2008, European heart journal.

[28]  Samuel Bernard,et al.  Evidence for Cardiomyocyte Renewal in Humans , 2008, Science.

[29]  Laura H. Smallwood,et al.  Scaling of muscle architecture and fiber types in the rat hindlimb , 2008, Journal of Experimental Biology.

[30]  T. Heck,et al.  Physical exercise improves plasmatic levels of IL-10, left ventricular end-diastolic pressure, and muscle lipid peroxidation in chronic heart failure rats. , 2008, Journal of applied physiology.

[31]  H. Tsutsui,et al.  Mitochondrial oxidative stress, DNA damage, and heart failure. , 2006, Antioxidants & redox signaling.

[32]  S. Góźdź,et al.  A cross-platform public domain PC image-analysis program for the comet assay. , 2003, Mutation research.

[33]  V. Veksler,et al.  Metabolic myopathy in heart failure. , 2002, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[34]  I. Sjaastad,et al.  Echocardiographic criteria for detection of postinfarction congestive heart failure in rats. , 2000, Journal of applied physiology.

[35]  M. Decramer,et al.  Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives. , 2000, The American journal of clinical nutrition.

[36]  D. Ganten,et al.  Selective activation of cardiac angiotensinogen gene expression in post-infarction ventricular remodeling in the rat. , 1993, Journal of molecular and cellular cardiology.

[37]  H. Drexler,et al.  Alterations of Skeletal Muscle in Chronic Heart Failure , 1992, Circulation.

[38]  C. H. Conrad,et al.  Intracellular calcium transients in myocardium from spontaneously hypertensive rats during the transition to heart failure. , 1991, Circulation research.

[39]  R. Tice,et al.  A simple technique for quantitation of low levels of DNA damage in individual cells. , 1988, Experimental cell research.

[40]  R. Armstrong,et al.  Muscle fiber type composition of the rat hindlimb. , 1984, The American journal of anatomy.

[41]  M. Pfeffer,et al.  Myocardial Infarct Size and Ventricular Function in Rats , 1979, Circulation research.

[42]  S. Silver,et al.  Heart Failure , 1937, The New England journal of medicine.

[43]  A. Collins The comet assay: a heavenly method! , 2015, Mutagenesis.

[44]  Hiroyuki Tsutsui,et al.  [Oxidative stress and heart failure]. , 2006, Nihon rinsho. Japanese journal of clinical medicine.

[45]  Melanie M. Choe,et al.  The comet assay: a method to measure DNA damage in individual cells , 2006, Nature Protocols.

[46]  P. Chang,et al.  Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[47]  C. H. Conrad,et al.  Direct effects of colchicine on myocardial function: studies in hypertrophied and failing spontaneously hypertensive rats. , 1999, Hypertension.