Abstract
Side stream cigarette smoke (SSCS) is known to be as harmful and hazardous to human health as is active smoking. In this study, we investigated the relationship between the exposure to SSCS and its stimulatory and subacute effects on the progression of non-alcoholic steatohepatitis (NASH). A methionine and choline-deficient plus high fat (MCDHF) diet was administered to C57BL/6 mice for 6 weeks. During the first three weeks of MCDHF diet feeding, each diet group was exposed to SSCS (0, 20, 40 µg/L) or fresh air for 2 hrs per day and 5 days per week. Additional experiments were performed by increasing the concentration (0, 30, 60 µg/L) and exposure time (6 hours per day) of SSCS. According to histopathologic analysis and serum levels of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), there were no differences in hepatic fat deposition, fibrosis, apoptosis or liver damage in MCDHF-fed mice based on SSCS exposure. There were also no differences in the expression of inflammation-, oxidative stress- or fibrosis-related genes between MCDHF-fed mice with or without SSCS exposure. Therefore, it is concluded that SSCS with current exposure amounts does not have additive detrimental effects on the early stage of NASH.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Valenti, V.E., de Abreu, L.C., Sato, M.A., Ferreira, C., Adami, F., Fonseca, F.L., Xavier, V., Godoy, M., Monteiro, C.B., Vanderlei, L.C. and Saldiva, P.H. (2012) Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle. BMC Cardiovasc. Disord., 12, 22.
Klatsky, A.L. and Armstrong, M.A. (1992) Alcohol, smoking, coffee, and cirrhosis. Am. J. Epidemiol., 136, 1248–1257.
Yu, M.W., Hsu, F.C., Sheen, I.S., Chu, C.M., Lin, D.Y., Chen, C.J. and Liaw, Y.F. (1997) Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am. J. Epidemiol., 145, 1039–1047.
Pessione, F., Ramond, M.J., Njapoum, C., Duchatelle, V., Degott, C., Erlinger, S., Rueff, B., Valla, D.C. and Degos, F. (2001) Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology, 34, 121–125.
Zein, C.O., Beatty, K., Post, A.B., Logan, L., Debanne, S. and McCullough, A.J. (2006) Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: A cross validated retrospective assessment. Hepatology, 44, 1564–1571.
Marrero, J.A., Fontana, R.J., Fu, S., Conjeevaram, H.S., Su, G.L. and Lok, A.S. (2005) Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J. Hepatol., 42, 218–224.
Fujita, Y., Shibata, A., Ogimoto, I., Kurozawa, Y., Nose, T., Yoshimura, T., Suzuki, H., Iwai, N., Sakata, R., Ichikawa, S. and Tamakoshi, A. (2006) The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma. Br. J. Cancer, 94, 737–739.
Jou, J., Choi, S.S. and Diehl, A.M. (2008) Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin. Liver Dis., 28, 370–379.
Tilg, H. and Moschen, A.R. (2010) Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology, 52, 1836–1846.
Zein, C.O., Unalp, A., Colvin, R., Liu, Y.C. and McCullough, A.J. (2011) Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease. J. Hepatol., 54, 753–759.
Azzalini, L., Ferrer, E., Ramalho, L.N., Moreno, M., Dominguez, M., Colmenero, J., Peinado, V.I., Barbera, J.A., Arroyo, V., Gines, P., Caballeria, J. and Bataller, R. (2010) Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats. Hepatology, 51, 1567–1576.
Friedman, T.C., Sinha-Hikim, I., Parveen, M., Najjar, S.M., Liu, Y., Mangubat, M., Shin, C.S., Lyzlov, A., Ivey, R., Shaheen, M., French, S.W. and Sinha-Hikim, A.P. (2012) Additive effects of nicotine and high-fat diet on hepatic steatosis in male mice. Endocrinology, 153, 5809–5820.
Ma, C. and Martins-Green, M. (2009) Second-hand cigarette smoke inhibits wound healing of the cornea by stimulating inflammation that delays corneal reepithelialization. Wound Repair Regen., 17, 387–396.
Ejaz, S. and Lim, C.W. (2006) Impact of sidestream whole smoke solutions on the outcome of wound repair and related angiogenesis. Environ. Toxicol. Pharmacol., 21, 308–316.
Marchetti, F., Rowan-Carroll, A., Williams, A., Polyzos, A., Berndt-Weis, M.L. and Yauk, C.L. (2011) Sidestream tobacco smoke is a male germ cell mutagen. Proc. Natl. Acad. Sci. U.S.A., 108, 12811–12814.
Yuan, H., Shyy, J.Y. and Martins-Green, M. (2009) Secondhand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1. J. Hepatol., 51, 535–547.
Theophilus, E.H., Keith Shreve, W., Ayres, P.H., Garner, C.D., Pence, D.H. and Swauger, J.E. (2007) Comparative 13-week cigarette smoke inhalation study in Sprague-Dawley rats: evaluation of cigarettes with two banded cigarette paper technologies. Food Chem. Toxicol., 45, 1076–1090.
Carmines, E.L., Gaworski, C.L., Faqi, A.S. and Rajendran, N. (2003) In utero exposure to 1R4F reference cigarette smoke: evaluation of developmental toxicity. Toxicol. Sci., 75, 134–147.
Kleiner, D.E., Brunt, E.M., Van Natta, M., Behling, C., Contos, M.J., Cummings, O.W., Ferrell, L.D., Liu, Y.C., Torbenson, M.S., Unalp-Arida, A., Yeh, M., McCullough, A.J. and Sanyal, A.J. (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, 41, 1313–1321.
Pihlajamaki, J., Kuulasmaa, T., Kaminska, D., Simonen, M., Karja, V., Gronlund, S., Kakela, P., Paakkonen, M., Kainulainen, S., Punnonen, K., Kuusisto, J., Gylling, H. and Laakso, M. (2012) Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans. J. Hepatol., 56, 663–670.
Fujita, K., Nozaki, Y., Yoneda, M., Wada, K., Takahashi, H., Kirikoshi, H., Inamori, M., Saito, S., Iwasaki, T., Terauchi, Y., Maeyama, S. and Nakajima, A. (2010) Nitric oxide plays a crucial role in the development/progression of nonalcoholic steatohepatitis in the choline-deficient, l-amino acid-defined diet-fed rat model. Alcohol. Cin. Exp. Res., 34 Suppl 1, S18–S24.
Neuschwander-Tetri, B.A. (2010) Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology, 52, 774–788.
Koliwad, S.K., Streeper, R.S., Monetti, M., Cornelissen, I., Chan, L., Terayama, K., Naylor, S., Rao, M., Hubbard, B. and Farese, R.V., Jr. (2010) DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation. J. Clin. Invest., 120, 756–767.
Yamaguchi, K., Yang, L., McCall, S., Huang, J., Yu, X.X., Pandey, S.K., Bhanot, S., Monia, B.P., Li, Y.X. and Diehl, A.M. (2007) Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology, 45, 1366–1374.
Alkhouri, N., Dixon, L.J. and Feldstein, A.E. (2009) Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert. Rev. Gastroenterol. Hepatol., 3, 445–451.
Gokulakrisnan, A., Jayachandran Dare, B. and Thirunavukkarasu, C. (2011) Attenuation of the cardiac inflammatory changes and lipid anomalies by (–)-epigallocatechin-gallate in cigarette smoke-exposed rats. Mol. Cell. Biochem., 354, 1–10.
Mari, M., Caballero, F., Colell, A., Morales, A., Caballeria, J., Fernandez, A., Enrich, C., Fernandez-Checa, J.C. and Garcia-Ruiz, C. (2006) Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab., 4, 185–198.
Lin, C., Rountree, C.B., Methratta, S., LaRusso, S., Kunselman, A.R. and Spanier, A.J. (2014) Secondhand tobacco exposure is associated with nonalcoholic fatty liver disease in children. Environ. Res., 132, 264–268.
Akhter, M.P., Lund, A.D. and Gairola, C.G. (2005) Bone biomechanical property deterioration due to tobacco smoke exposure. Calcif. Tissue Int., 77, 319–326.
Kruger, F.C., Daniels, C., Kidd, M., Swart, G., Brundyn, K., Van Rensburg, C. and Kotze, M.J. (2010) Non-alcoholic fatty liver disease (NAFLD) in the Western Cape: a descriptive analysis. S. Afr. Med. J., 100, 168–171.
Mueller, D., Schulze, J., Ackermann, H., Klingelhoefer, D., Uibel, S. and Groneberg, D.A. (2012) Particulate matter (PM) 2.5 levels in ETS emissions of a Marlboro Red cigarette in comparison to the 3R4F reference cigarette under open- and closed-door condition. J. Occup. Med. Toxicol., 7, 14.
Coultas, D.B., Samet, J.M., McCarthy, J.F. and Spengler, J.D. (1990) Variability of measures of exposure to environmental tobacco smoke in the home. Am. Rev. Respir. Dis., 142, 602–606.
Sureda, X., Fernandez, E., Lopez, M.J. and Nebot, M. (2013) Secondhand tobacco smoke exposure in open and semi-open settings: a systematic review. Environ. Health Perspect., 121, 766–773.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://doi.org/creativecommons.org/licenses/by/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Kim, J.W., Yun, H., Choi, SJ. et al. Evaluating the Influence of Side Stream Cigarette Smoke at an Early Stage of Non-Alcoholic Steatohepatitis Progression in Mice. Toxicol Res. 33, 31–41 (2017). https://doi.org/10.5487/TR.2017.33.1.031
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.5487/TR.2017.33.1.031