Effects of N Ethyl N′ nitrosourea in mice brain in time fashion

Effect of ENU in brain

Authors

  • Priyatosh Nath Immunology Microbiology Lab, Department of Human Physiology, Tripura University, Tripura India
  • Snehashish Modak Immunology Microbiology Lab, Department of Human Physiology, Tripura University, Tripura. India
  • Tamanna Akter Immunology Microbiology Lab, Department of Human Physiology, Tripura University, Tripura India
  • Debasish Maiti Tripura University

DOI:

https://doi.org/10.55184/ijpas.v74i1.34

Keywords:

Antioxidant enzyme, Oxidative stress, N-Ethyl-N-Nitrosourea (ENU), neurotoxicity

Abstract

Antioxidant enzyme plays a pivotal role in preventing oxidative stress. Chemical toxicants often exert adverse effects in the biological system by breaking the antioxidant response system leading to severe oxidative stress. N-Ethyl-N-Nitrosourea (ENU) is a DNA alkylating agent and is carcinogenic and neurotoxic in animals. ENU in the nervous system cause persistent alkylation of DNA within the neurons altering the normal functional activities of the brain. Prenatal exposure to ENU in rodents that generate malignant gliomas in the brain induces functional changes and apoptotic death in neuronal progenitors in the brain's subventricular zone (SVZ). However, as chemical toxicants, their role in the induction of oxidative stress in brain tissue and subsequent change in the brain were less studied. In this study, we have investigated the response antioxidant system and induction of oxidative stress in the Balb/c mice brain at various time points after ENU exposure. Exposures to ENU were found to raise the oxidative stress and lipid peroxidation in the brain of mice with subsequent reduction in antioxidant enzyme activity. A significant increase in lactate dehydrogenase activity in the serum and brain homogenate was recorded at 16th weeks after ENU injection, which indicates metabolic alteration due to damage in the brain and has been validated by histological damage in the cerebral cortex and abnormal neurologic behavior in animals administered with ENU.

References

Justice MJ, Mutagenesis of the mouse germline, in: I Jackson, C Abbott (Eds.), Mouse Genetics and Transgenics: A Practical Approach, Oxford: Oxford University Press, 1999.

Nazmeen A, Maiti S. Oxidant stress induction and signalling in xenografted (human breast cancer-tissues) plus estradiol treated or N-ethyl-N-nitrosourea treated female rats via altered estrogen sulfotransferase (rSULT1E1) expressions and SOD1/catalase regulations. Mol Biol Rep. 2018 Dec;45(6):2571-2584. doi: 10.1007/s11033-018-4425-z. Epub 2018 Oct 12.

Mukherjee J, Sarkar S, Ghosh A, Duttagupta AK, Chaudhuri S (2004). Immunotherapeutic effects of T11TS/S-LFA3 against nitrosocompound mediated neural genotoxicity. Toxicol Lett 150: 239–257.

Sareddy GR, Challa S, Panigrahi M, Babu PP (2009) Wnt/beta-catenin/Tcf signaling pathway activation in malignant progression of rat gliomas induced by transplacental N-ethyl-N-nitrosourea exposure. Neurochem Res 34: 1278–1288.

Barth RF, Kaur B (2009) Rat brain tumor models in experimental neurooncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. J Neurooncol 94: 299–312.

Leonard JR, D’Sa C, Klocke BJ, Roth KA (2001) Neural precursor cell apoptosis and glial tumorigenesis following transplacental ethyl-nitrosoureaexposure. Oncogene 20: 8281–8286.

Slikker W, 3rd, Mei N, Chen T (2004) N-ethyl-N-nitrosourea (ENU) increased brain mutations in prenatal and neonatal mice but not in the adults. Toxicol Sci 81: 112–120.

Capilla-Gonzalez V, Gil-Perotin S, Garcia-Verdugo JM (2010) Postnatal exposure to N-ethyl-N-nitrosurea disrupts the subventricular zone in adult rodents. Eur J Neurosci.

Capilla-Gonzalez1 V, Gil-Perotin S, Ferragud A, Bonet-Ponce L,Canales JJ, Garcia-Verdugo JM. Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites. PLoS ONE, 2012; 7(1): e29891. doi:10.1371/journal.pone.0029891

Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga AM. ROS and Brain Diseases: The Good, the Bad, and the Ugly. Oxidative Medicine and Cellular Longevity; 2013, Article ID 963520. http://dx.doi.org/10.1155/2013/963520

M. Guglielmotto, E. Tamagno, and O. Danni, “Oxidative stress and hypoxia contribute to Alzheimer’s disease pathogenesis: two sides of the same coin,” The Scientific World Journal, vol. 9, no. 1, pp. 781–791, 2009.

S.-D. Chen, D.-I. Yang, T.-K. Lin, F.-Z. Shaw, C.-W. Liou, and Y.-C. Chuang, “Roles of oxidative stress, apoptosis, PGC-1 and mitochondrial biogenesis in cerebral ischemia,” International Journal of Molecular Sciences, vol. 12, no. 10, pp. 7199–7215, 2011.

M. Valko, D. Leibfritz, J. Moncol, M. T. D. Cronin, M. Mazur, and J. Telser, “Free radicals and antioxidants in normal physiological functions and human disease,” International Journal of Biochemistry and Cell Biology 2007; 39 (1): 4–84.

T.M.Michel, D. P¨ulschen, and J.Thome, “The role of oxidative stress in depressive disorders,” Current Pharmaceutical Design,vol. 18, no. 36, pp. 5890–5899, 2012.

Silig Y, Ozdemir O, Atalay A. Liver and colon pro- and anti-oxidant enzyme activities in rats after long-term ethylnitrosourea exposure. Indian J Biochem Biophys. 2003 Apr;40(2):136-8.

Nazmeen A, Maiti S. Oxidant stress induction and signalling in xenografted (human breast cancer-tissues) plus estradiol treated or N-ethyl-N-nitrosourea treated female rats via altered estrogen sulfotransferase (rSULT1E1) expressions and SOD1/catalase regulations. Mol Biol Rep. 2018 Dec;45(6):2571-2584. doi: 10.1007/s11033-018-4425-z. Epub 2018 Oct 12.

Beauchamp C, Fridovich I. Superoxide Dismutase: Improved Assays and an Assay Applicable to Acrylamide Gels. Analytical Biochemistry 1791; 44: 276-287.

Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-6. doi: 10.1016/s0076-6879(84)05016-3.

Paglia D E & Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 1967; 70:158-69.

Gupta R, Dubey DK, Kannan GM, Flora SJS. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse. Cell Biol Int. 2007;31: 44–56.

Buege JA, Aust SD. Microsomal lipid peroxidation. Biomembranes-Part C: Biological oxidations 1978; 30: 302-310.Doi:10.1016/s0076-6879(78)52032-6.

Wróblewski F, and Ladue JS. Lactic Dehydrogenase Activity in Blood. Exp Biol Med (Maywood) 1955; 90: 210-213. DOI: 10.3181/00379727-90-21985

Simaga S, Abramic M, Osmak M, Babic D, Ilic-Forko J. Total tissue lactate dehydrogenase activity in endometrial carcinoma. Int J Gynecol Cancer 2008, 18, 1272–1278. doi:10.1111/j.1525-1438.2008.01196.x

Fischer AH, Jacobson KA, Rose J, Zeller R. Cryosectioning Tissues. Cold Spring Harb Protoc 2008; pdb.prot4991. doi:10.1101/pdb.prot4991

Knapp LT and Klann E (2002) Role of reactive oxygen species in hippocampal long term potentiation: contributory or inhibitory? J Neurosci Res 70:1–7.

Ehrenbrink G, Hakenhaar FS, Salomon TB, Petrucci AP, Sandri MR, Benfato MS. Antioxidant enzyme activities and protein damage in rat brain of both sexes. Experimental Gerontology 2006; 41(4): 368-371. https://doi.org/10.1016/j.exger.2006.02.007

Ceretta LB, Reus GZ, Abelaira HM, Ribeiro KF, Zappellini G, Felisbino FF, Steckert AV, Dal-Pizzol F, Quevedo J. Increased oxidative stress and imbalance in antioxidant enzymes in the brain of alloxan induced diabetic rats. Journal of Diabetes Research 2012; Article Id302682. https://doi.org/10.1155/2012/302682.

Kadeyala PK, Sannadi S, Gottipolu RR. Alterations in apoptotic caspases and antioxidant enzymes in arsenic exposed rat brain regions: Reversal effect of essential metals and chelating agent. Environmental toxicology and pharmacology2013; 36(3): 1150-1166. https://doi.org/10.1016/j.etap.2013.09.021

Singla N, Dhawan DK. N-methyl N-nitrosourea induced functional and structural alterations in mice brain-role of curcumin. Neurotox res. 2012; 22(2): 115-126. https://doi.org/10.1007/s12640-011-9307-2

He L, He T, Farrar S, Ji L, Liu T, Ma X. Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cellular Physiology and Biochemistry 2017;44:532–553. https://doi.org/10.1159/000485089

Hulbert AJ, Pamplona R, Buffenstein R, and Buttemer WA (2007) Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev 87: 1175–1213.

Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga Ana-M. ROS and Brain Diseases: The Good, the Bad, and the Ugly. Oxidative Medicine and Cellular Longevity 2013, Article ID 963520. http://dx.doi.org/10.1155/2013/963520

Klein R, Nagy O, To´thova´ C, Chovanova F. Clinical and Diagnostic Significance of Lactate Dehydrogenase and Its Isoenzymes in Animals. Veterinary Medicine International 2020; 5346483: 1-11. https://doi.org/10.1155/2020/5346483

Rao CJ, Shukla PK, Mohanty S, Reddy YJV. Predictive value of serum lactate dehydrogenase in head injury. Journal of Neurology, Neurosurgery, and Psychiatry 1978; 41: 948-953. DOI: 10.1136/jnnp.41.10.948

Zheng S, Wang H, Guorong Chen, Shangguan H, Yu L, Lin Z, Lin Y, Yao P, Kang D. Higher Serum Levels of Lactate Dehydrogenase Before Microsurgery Predict Poor Outcome of Aneurysmal Subarachnoid Hemorrhage. Front. Neurol. 2021; 12: 720574. https://doi.org/10.3389/fneur.2021.720574

Tilson HA, Mitchell CL (1984) Neurobehavioral techniques to assess the effects of chemicals on the nervous system. Annu Rev Pharmacol Toxicol 24:425–450.

Published

23-03-2022

How to Cite

Nath, P., Modak, S., Akter, T., & Maiti, D. (2022). Effects of N Ethyl N′ nitrosourea in mice brain in time fashion: Effect of ENU in brain. INDIAN JOURNAL OF PHYSIOLOGY AND ALLIED SCIENCES, 74(1). https://doi.org/10.55184/ijpas.v74i1.34