N-acetylcysteine relieves oxidative stress and protects hippocampus of rat from radiation-induced apoptosis by inhibiting caspase-3.

It has been recognized that radiation-induced effects remain a significant risk. An accumulation of reactive oxygen species (ROS) is considered to be one factor that contributes to neurodegenerative changes. The aim of our study was to investigate the potential radioprotective effects of NAC. Male Sprague-Dawley rats underwent radiation. Irradiation was performed at room temperature with a 4-Gy dose of radiation. A dose of N-acetylcysteine (NAC) was performed 15 min prior to irradiation intraperitoneally. The methods of immunohistochemistry, TUNEL staining, Nissl staining, qRT-PCR, analysis of reactive oxygen species and Western blot were performed. In conclusion, our results demonstrate that NAC inhibits apoptosis induced by irradiation via the inhibition of caspase-3. We demonstrated a decrease in caspase-3 mRNA that was present at 24h of NAC treatment. Such mRNA decrease was accompanied by a decrease of protein. In the present study, NAC effectively antagonized oxidation induced by irradiation. These results provide evidence that the neural protective effect and the antioxidant effect of NAC contribute to metabolic activity.

[1]  R. Schiestl,et al.  Effect of N-Acetyl Cysteine on Oxidative DNA Damage and the Frequency of DNA Deletions in Atm-Deficient Mice , 2004, Cancer Research.

[2]  H. Mansour,et al.  Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. , 2008, Biochemical pharmacology.

[3]  M. Lynch,et al.  Age-related changes in oxidative mechanisms and LTP are reversed by dietary manipulation , 1999, Neurobiology of Aging.

[4]  F. Fan,et al.  Tat-SmacN7 induces radiosensitization in cancer cells through the activation of caspases and induction of apoptosis. , 2013, International journal of oncology.

[5]  J. Leszek,et al.  Vascular oxidative stress and mitochondrial failure in the pathobiology of Alzheimer's disease: a new approach to therapy. , 2013, CNS & neurological disorders drug targets.

[6]  Hae-June Lee,et al.  Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis. , 2008, Journal of radiation research.

[7]  C. Filesi,et al.  Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. , 2005, The Journal of nutritional biochemistry.

[8]  E. Rudakova,et al.  N-acetylcysteine prevents electrical remodeling and attenuates cellular hypertrophy in epicardial myocytes of rats with ascending aortic stenosis , 2012, Basic Research in Cardiology.

[9]  Xueying Sun,et al.  Hydrogen sulfide protects cardiomyocytes from myocardial ischemia-reperfusion injury by enhancing phosphorylation of apoptosis repressor with caspase recruitment domain. , 2012, The Tohoku journal of experimental medicine.

[10]  M. Zamani,et al.  Neuroprotective effect of olive oil in the hippocampus CA1 neurons following ischemia: Reperfusion in mice , 2013, Journal of neurosciences in rural practice.

[11]  Barry Halliwell,et al.  Reactive Oxygen Species and the Central Nervous System , 1992, Journal of neurochemistry.

[12]  M. Mckee,et al.  Organometal-induced increases in oxygen reactive species: the potential of 2',7'-dichlorofluorescin diacetate as an index of neurotoxic damage. , 1990, Toxicology and applied pharmacology.

[13]  S. Chakravarthi,et al.  N-acetylcysteine Offers Cardioprotection by Decreasing Cardiac Lipid Hydroperoxides and 8-Isoprostane Level in Isoproterenol-Induced Cardiotoxicity in Rats , 2011, Cardiovascular Toxicology.

[14]  K. Trott,et al.  The effects of low-dose X-irradiation on the oxidative burst in stimulated macrophages , 2002, International journal of radiation biology.

[15]  O. Aruoma,et al.  The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. , 1989, Free radical biology & medicine.

[16]  M. Frassanito,et al.  Regulation of mRNA caspase-8 levels by anti-nuclear autoantibodies , 2010, Clinical and Experimental Medicine.

[17]  G. Gores,et al.  Apoptotic Body Engulfment by a Human Stellate Cell Line Is Profibrogenic , 2003, Laboratory Investigation.

[18]  Sung-Ho Kim,et al.  Neurobiological toxicity of radiation in hippocampal cells. , 2013, Histology and histopathology.

[19]  T. Parasassi,et al.  Human cell membrane oxidative damage induced by single and fractionated doses of ionizing radiation: a fluorescence spectroscopy study. , 1998, International journal of radiation biology.

[20]  Michael Berk,et al.  The chemistry and biological activities of N-acetylcysteine. , 2013, Biochimica et biophysica acta.

[21]  Ying-ying Jing,et al.  Autophagy prevents irradiation injury and maintains stemness through decreasing ROS generation in mesenchymal stem cells , 2013, Cell Death and Disease.

[22]  Li-Li Zuo,et al.  The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease. , 2013, Gene.

[23]  R. Liddington,et al.  Structural Basis for the Inhibition of Caspase-3 by XIAP , 2001, Cell.

[24]  Rebecca C Taylor,et al.  Apoptosis: controlled demolition at the cellular level , 2008, Nature Reviews Molecular Cell Biology.

[25]  S. Flora,et al.  N‐acetyl‐l‐cysteine , 1993, Journal of cellular biochemistry. Supplement.

[26]  N. Ercal,et al.  Antioxidant role of N-acetyl cysteine isomers following high dose irradiation. , 2003, Free radical biology & medicine.

[27]  S. Ohmori,et al.  Effects of age on levels of cysteine, glutathione and related enzyme activities in livers of mice and rats and an attempt to replenish hepatic glutathione level of mouse with cysteine derivatives , 1996, Mechanisms of Ageing and Development.

[28]  C. Shyamaladevi,et al.  Protective effect of N-acetylcysteine against gamma ray induced damages in rats--biochemical evaluations. , 2002, Indian journal of experimental biology.

[29]  T. Matsushita,et al.  The overexpression of SIRT1 inhibited osteoarthritic gene expression changes induced by interleukin‐1β in human chondrocytes , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  T. Boeckers,et al.  Small-Molecule XIAP Inhibitors Enhance γ-Irradiation-Induced Apoptosis in Glioblastoma , 2009 .

[31]  Rajesh Arora,et al.  Radioprotection by plant products: present status and future prospects , 2005, Phytotherapy research : PTR.

[32]  G. Jagetia.  Radioprotective Potential of Plants and Herbs against the Effects of Ionizing Radiation. , 2007 .

[33]  Y. Lazebnik,et al.  Caspases: enemies within. , 1998, Science.

[34]  John Calvin Reed,et al.  X-linked Inhibitor of Apoptosis Protein (XIAP) Inhibits Caspase-3 and -7 in Distinct Modes* , 2001, The Journal of Biological Chemistry.

[35]  S. Shukla,et al.  Toxic effects of lead exposure in rats: involvement of oxidative stress, genotoxic effect, and the beneficial role of N-acetylcysteine supplemented with selenium. , 2014, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer.

[36]  Marcos Martı́nez,et al.  N-Acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondria , 2000, Brain Research.

[37]  R. Ratcheson,et al.  Caspase-9 Inhibition after Focal Cerebral Ischemia Improves Outcome following Reversible Focal Ischemia , 2002, Metabolic Brain Disease.