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Volume 10, Issue 3 (Vol.10 No.3 Oct 2021)
rbmb.net 2021, 10(3): 429-436 |
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Mahmoud A A, Abdel-Aziz H, Elbadr M, ELBadre H. Effect of Nicotine on STAT1 Pathway and Oxidative Stress in Rat Lungs. rbmb.net 2021; 10 (3) :429-436
URL: http://rbmb.net/article-1-680-en.html
URL: http://rbmb.net/article-1-680-en.html
Department of Medical Biochemistry, Faculty of Medicine, Sohag University, Egypt.
Abstract: (2826 Views)
Background: Tobacco use is responsible for millions of preventable deaths due to cancer. Nicotine, an alkaloid chemical found in tobacco was proved to cause chronic inflammation and oxidative stress. The transcription factor STAT1 induces the expression of many proinflammatory genes and has been suggested to be a target for anti-inflammatory therapeutics. The following study investigated the effect of Nicotine on STAT1 pathway and oxidative stress in rat lung tissue.
Methods: Thirty rats were divided into 3 groups; group I considered as control, group II; its rats were daily injected with Nicotine at a dose of 0.4 mg/100 gm body for 8 successive weeks and group III; its rats were daily injected with Nicotine as group II, but the injection was stopped for another 4
weeks. STAT1α protein was assessed by immunohistochemistry, COX-2 and iNOS genes expression were evaluated by real time PCR and thiobarbituric acid reactive substances (TBARS) and total thiols were measured using spectrophotometric methods in the lung tissues of the rats.
Results: The results of the study revealed that group II rats had the highest expression of STAT1α protein and COX-2 and iNOS genes and oxidative stress in their lung tissues. Nicotine cessation for 4 weeks caused a marked reduction in the expression of STAT1α protein, COX-2 and iNOS genes and oxidative stress.
Conclusions: Induction of STAT1 pathway and the increase in oxidative stress may be the mechanisms through which Nicotine may induce its harmful effects.
Methods: Thirty rats were divided into 3 groups; group I considered as control, group II; its rats were daily injected with Nicotine at a dose of 0.4 mg/100 gm body for 8 successive weeks and group III; its rats were daily injected with Nicotine as group II, but the injection was stopped for another 4
weeks. STAT1α protein was assessed by immunohistochemistry, COX-2 and iNOS genes expression were evaluated by real time PCR and thiobarbituric acid reactive substances (TBARS) and total thiols were measured using spectrophotometric methods in the lung tissues of the rats.
Results: The results of the study revealed that group II rats had the highest expression of STAT1α protein and COX-2 and iNOS genes and oxidative stress in their lung tissues. Nicotine cessation for 4 weeks caused a marked reduction in the expression of STAT1α protein, COX-2 and iNOS genes and oxidative stress.
Conclusions: Induction of STAT1 pathway and the increase in oxidative stress may be the mechanisms through which Nicotine may induce its harmful effects.
Type of Article: Original Article |
Subject:
Biochemistry
Received: 2021/04/3 | Accepted: 2021/05/13 | Published: 2021/12/5
Received: 2021/04/3 | Accepted: 2021/05/13 | Published: 2021/12/5
References
1. Counts ME, Morton MJ, Laffoon SW, R H Cox, P J Lipowicz. Smoke composition and predicting relationships for international commercial cigarettes smoked with three machine-smoking conditions. Regul Toxicol Pharmacol. 2005;41:(3):185-227. [DOI:10.1016/j.yrtph.2004.12.002] [PMID]
2. Schaal C, Chellappan S. Nicotine-Mediated Regulation of Nicotinic Acetylcholine Receptors in Non-Small Cell Lung Adenocarcinoma by E2F1 and STAT1 Transcription Factors. PloS one. 2016;11(5):e0156451. [DOI:10.1371/journal.pone.0156451] [PMID] [PMCID]
3. Dasgupta P, Rastogi S, Pillai S, Dalia Ordonez-Ercan, Mark Morris, Eric Haura, et al. Nicotine induces cell proliferation by beta arrestin-mediated activation of Src and Rb-Raf-1 pathways. J Clin Invest. 2006;116(8):2208-2217. [DOI:10.1172/JCI28164] [PMID] [PMCID]
4. Wang HY, Lee DH, Davis CB, Shank RP. Amyloid peptide Abeta (1-42) binds selectively and with picomolar affinity to alpha7 nicotinic acetylcholine receptors. J Neurochem. 2000;75(3):1155-61. [DOI:10.1046/j.1471-4159.2000.0751155.x] [PMID]
5. Baris S, Alroqi F, Kiykim A, Karakoc-Aydiner E, Ogulur I, Ozen A, et al. Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1. J Clin Immunol. 2016;36(7):641-8. [DOI:10.1007/s10875-016-0312-3] [PMID] [PMCID]
6. Ebner FH, Mariotto S, Darra E, H Suzuki, E Cavalieri. Use of STAT1 inhibitors in the treatment of brain I/ R injury and neurodegenerative diseases. Cen Nerv Syst Agents Med Chem. 2011;11(1):2-7. [DOI:10.2174/187152411794961077] [PMID]
7. Wang H, Zhang Y, Xia F, Zhang W, Chen P, Yang G, et al. Protective effect of silencing STAT1 on high glucose-induced podocytes injury via Forkhead transcription factor O1-regulated the oxidative stress response. BMC Mol and Cell Biol. 2019;20. [DOI:10.1186/s12860-019-0209-0] [PMID] [PMCID]
8. Schindler C, Fu XY, Improta T, R Aebersold, J E Darnell Jr. Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992;89(16):7836-9. [DOI:10.1073/pnas.89.16.7836] [PMID] [PMCID]
9. Baran-Marszak F, Feuillard J, Najjar I, Clorennec CL, Béchet JM, Dusanter-Fourt I, et al. Differential roles of STAT1alpha and STAT1beta in fludarabine-induced cell cycle arrest and apoptosis in human B cells. Blood. 2004;104(8): 2475-83. [DOI:10.1182/blood-2003-10-3508] [PMID]
10. Sayed Abdel-Tawab M, Mostafa Tork O, Mostafa-Hedeab G, Ewaiss Hassan M, Azmy Elberry D. Protective Effects of Quercetin and Melatonin on Indomethacin Induced Gastric Ulcers in Rats. rbmb.net. 2020; 9 (3) :278-290. [DOI:10.29252/rbmb.9.3.278] [PMID] [PMCID]
11. Islam T, Breton C, Salam MT, Rob McConnell, Made Wenten, W James Gauderman, et al. Role of inducible nitric oxide synthase in asthma risk and lung function growth during adolescence. Thorax. 2010;65(2):139-45. [DOI:10.1136/thx.2009.114355] [PMID]
12. Chen CW, Chang YH, Tsi CJ. et al. Inhibition of IFN-gamma-mediated inducible nitric oxide synthase induction by the peroxisome proliferator-activated receptor gamma agonist, 15-deoxy-delta 12,14-prostaglandin J2, involves inhibition of the upstream Janus kinase/STAT1 signaling pathway. J. Immunol. 2003; 171: 979-988 [DOI:10.4049/jimmunol.171.2.979] [PMID]
13. de Prati AC, Ciampa AR, Cavalieri E, et al. STAT1 as a new molecular target of anti-inflammatory treatment. Current medicinal chemistry. 2005; 12: 1819-1828. [DOI:10.2174/0929867054546645] [PMID]
14. Aydos, K., Guven, M. C., Can, B., et al. Nicotine toxicity to the ultrastructure of the testis inrats. BJU International.2001; 88:622-626. [DOI:10.1046/j.1464-4096.2001.02384.x] [PMID]
15. Draper, H.H., Hadley, M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. (1990; 186: 421 431. [DOI:10.1016/0076-6879(90)86135-I]
16. Riddles P.W., Blakeley R.L., Zerner B. Reassessment of Ellman's Reagent Methods in Enzymology. 1983; 91 (C): 49-60. [DOI:10.1016/S0076-6879(83)91010-8]
17. Coussens, L.M., Werb, Z. Inflammation and cancer. Nature. 2002;420: 860-7. [DOI:10.1038/nature01322] [PMID] [PMCID]
18. Gomes, M., Teixeira, A. L., Coelho, A., et al. The role of inflammation in lung cancer. Advances in experimental medicine and biology. 2014; 816: 1-23 [DOI:10.1007/978-3-0348-0837-8_1] [PMID]
19. Akram, M., Kim, K.A., Kim, E.S., et al. Selective inhibition of JAK2/STAT1 signaling and iNOS expression mediates the anti-inflammatory effects of coniferyl aldehyde. Chem Biol Interact. 2016; 256: 102-10. [DOI:10.1016/j.cbi.2016.06.029] [PMID]
20. Bozeman R, Abel EL, Macias E, Cheng T, Beltran L, DiGiovanni J, et al. A novel mechanism of skin tumor promotion involving interferon-gamma (IFNγ)/signal transducer and activator of transcription-1 (STAT1) signaling. Molecular carcinogenesis 2015; 54: 642-653. [DOI:10.1002/mc.22132] [PMID] [PMCID]
21. Moon H, White AC, Borowsky AD. New insights into the functions of Cox-2 in skin and esophageal malignancies. Exp Mol Med. 2020;52(4):538-547 [DOI:10.1038/s12276-020-0412-2] [PMID] [PMCID]
22. Huang RY, Chen GG. Cigarette smoking, cyclooxygenase-2 pathway and cancer. Biochim Biophys Acta. 2011;1815(2):158-69. [DOI:10.1016/j.bbcan.2010.11.005] [PMID]
23. Elisia I, Lam V, Cho B, Hay M, Li MY, Yeung M, et al. The effect of smoking on chronic inflammation, immune function and blood cell composition. Sci Rep. 2020;10(1):19480. [DOI:10.1038/s41598-020-76556-7] [PMID] [PMCID]
24. Hu Y, Tang J, Hou S, Shi X, Qin J, Zhang T, et al. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX 2, TGF β1/2, MMP 9 and BDNF in a rat model. Mol Med Rep. 2017;16(5):6864-6869. [DOI:10.3892/mmr.2017.7464] [PMID]
25. Chen YC, Shen SC, Lin HY, Tsai SH, Lee TJF. Nicotine enhancement of lipopolysaccharide/interferon-gamma-induced cytotoxicity with elevating nitric oxide production. Toxicol Lett. 2004;153(2):191-200. [DOI:10.1016/j.toxlet.2004.01.014] [PMID]
26. Wetscher GJ, Bagchi M, Bagchi D, Perdikis G, Hinder PR, Glaser K, et al. Free radical production in nicotine treated pancreatic tissue. Free Radic Biol Med.1995;18(5):877-82. [DOI:10.1016/0891-5849(94)00221-5]
27. Yildiz D, Liu YS, Ercal N, Armstrong DW. Comparison of pure nicotine- and smokeless tobacco extract-induced toxicities and oxidative stress. Arch Environ Contam Toxicol. 1999;37(4):434-9. [DOI:10.1007/s002449900537] [PMID]
28. Bhagwat SV, Vijayasarathy C, Raza H, J Mullick, NG Avadhani. Preferential effects of nicotine and 4-(N-methyl-Nnitrosamine)-1-(3-pyridyl)-1-butanone on mitochondrial glutathione S-transferase A4-4 induction and increased oxidative stress in the rat brain. Biochem Pharmacol. 1998;56(7):831-9. [DOI:10.1016/S0006-2952(98)00228-7]
29. Helen A, Krishnakumar K, Vijayammal PL, Augusti KT. Antioxidant effect of onion oil (Allium cepa. Linn) on the damages induced by nicotine in rats as compared to alpha-tocopherol. Toxicol Lett. 2000;116(1-2):61-8. [DOI:10.1016/S0378-4274(00)00208-3]
30. Kalra J, Chaudhary AK, Prasad K. Increased production of oxygen free radicals in cigarette smokers. Int J Exp Pathol. 1991; 72: 1-7.
31. Altuntas I, Dane S, Gumustekin K. Effects of cigarette smoking on lipid peroxidation. J Basic Clin Physiol Pharmacol. 2002;13(1):69-72. [DOI:10.1515/JBCPP.2002.13.1.69] [PMID]
32. Cheraghi M, Ahmadvand H, Maleki A, Babaeenezhad E, Shakiba S, Hassanzadeh F. Oxidative Stress Status and Liver Markers in Coronary Heart Disease. Rep Biochem Mol Biol. 2019;8(1):49-55.
33. Balcerczyk A, Bartosz G. Thiols are main determinants of total antioxidant capacity of cellular homogenates. Free Radic Res. 2003;37(5):537-41. [DOI:10.1080/1071576031000083189] [PMID]
34. Ahmed Mobasher M, Galal El-Tantawi H, Samy El-Said K. Metformin Ameliorates Oxidative Stress Induced by Diabetes Mellitus and Hepatocellular Carcinoma in Rats. Rep Biochem Mol Biol. 2020;9(1):115-128 [DOI:10.29252/rbmb.9.1.115] [PMID] [PMCID]
35. Kuschner WG, D'Alessandro A, Wong H, P D Blanc. Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. Eur Respir J.1996;9(10):1989-94. [DOI:10.1183/09031936.96.09101989] [PMID]
36. Chaudhuri R, Livingston E, McMahon AD, Lafferty J, Fraser I, Spears M, et al. McMahon AD, et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med. 2006;174(2):127-33. [DOI:10.1164/rccm.200510-1589OC] [PMID]
37. Westergaard CG, Porsbjerg C, Backer V. The effect of smoking cessation onairway inflammation in young asthma patients. Clin Exp Allergy. 2014;44(3):353-61. [DOI:10.1111/cea.12243] [PMID]
38. Hogman M, Holmkvist T, Walinder R, Meriläinen P, Lúdvíksdóttir D, Håkansson L, et al. Increased nitric oxide elimination from the airways after smoking cessation. Clin Sci (Lond). 2002;103(1):15-9. [DOI:10.1042/cs1030015] [PMID]
39. Rennard SI, Daughton D, Fujit J, Oehlerking MB, Dobson JR, Stahl MG, et al. Short-term smoking reduction is associated with reduction in measures of lower respiratory tract inflammation in heavy smokers. Eur Respir J. 1990;3(7):752-9.
40. Karimi R, Tornling G, Grunewald J, et al. Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on cumulative smoking history. PloS one. 2012;7(3):e34232. [DOI:10.1371/journal.pone.0034232] [PMID] [PMCID]
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