CARBON TETRACHLORIDE ADMINISTRATION INDUCES THE EXPRESSION OF HYPOXIA INDUCIBLE FACTOR-1α (HIF-1α) IN RAT LIVER

Lindi G Haritsyah, Mohamad Sadikin, Sri Widia Jusman

Abstract


Background: There is now increasing evidence that HIF-1 is also responsive to a variety of non-hypoxic stimuli. However, the mechanisms by which these non-hypoxic stimuli induce HIF-1α are not completely known, yet, although some evidence points to a role of ROS as messengers regulating HIF activity.

Objective: To determine the expression of HIF-1α in liver rat tissue induced by carbon tetrachloride under normoxic conditions, with or without N-acetylcysteine protection.

Methods: Twenty five male Sprague-Dawley rats were divided into 5 group: normal control rats, normal rats orally administered with coconut oil (1 mL/200 g body weight) for 1 day, rats orally administered with CCl4 (0.55 mg/g body weight) for 1 day, rats injected i.v. with NAC (0.15 mg/g body weight) for 8 days and then orally administered with CCl4 (0.55 mg/g body weight) for 1 day, rats orally administered with CCl4 (0.55 mg/g body weight) for 1 day and then injected i.v. with NAC (0.15 mg/g body weight) for 2 days. The expression of HIF-1α mRNA was measured by real-time RT-PCR using the Livak method. The expression of HIF-1α protein was measured by ELISA assay.

Results: The highest HIF-1α mRNA and protein expression found in the group treated by CCl4 and then was gradually lowered in the pre-NAC group, post-NAC group, control group, and last, in the oil group.

Conclusion : Our study shows the effect of CCl4-treated rats under normoxic conditions increased the mRNA and protein HIF-1α. NAC post-treatment provide a better protective effect compared with NAC pre-treatment


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References


Jones DP. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol. 2008;295:C849–C868.

Szymonik-Lesiuk S, Czechowska G, Stryjecka-Zimmer M, Slomka M, Madro A, Celinski K, et al. Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. J. Hepatobiliary Pancreat Surg. 2003;10:309–315.

Agency for Toxic Substances and Disease Registry (ATSDR) & the Environmental Protection Agency (EPA). Toxicological profile for carbon tetrachloride [Online]. 2005 [cited 2009 Sep 9]. Available from: URL:www.atsdr.cdc.gov/ToxProfiles/tp30.pdf

Manibusan MK, Odin M, Eastmond DA. Postulated carbon tetrachloride mode of action: a review. Journal of Environmental Science and Health, Part C. 2007;25(3):185–209.

Kaluz S, Kaluzová M, Stanbridge EJ. Regulation of gene expression by hypoxia: Integration of the HIF transduced hypoxic signal at the hypoxia-responsive element. Clin. Chim. Acta. 2008;395(1-2): 6–13.

Morel Y & Barouki R. Repression of gene expression by oxidative stress. Biochem. J. 1999;342:481–496.

Giaccia AJ, Simon MC, Johnson R. The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease. Genes & Development. 2004;18:2183–2194.

Giordano FJ. Oxygen, oxidative stress, hypoxia and heart failure. J. Clin. Invest. 2005;115:500–508.

Kietzmann T & Gorlach A. Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Seminars in Cell & Developmental. 2005;16:474–486.

Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW. Hypoxia-inducible factor (HIF-1)α: its protein stability and biological function. Experimental and Molecular Medicine. 2004;36(1):1–12.

Muriel P, Alba N, Perez-Alvarez VM, Shibayama M, Tsutsumi VM. Kupffer cells inhibition prevents hepatic lipid peroxidation and damage induced by carbon tetrachloride. Comparative Biochemistry and Physiology Part C. 2001;130:219–226.

Jiang Y, Liu J, Waalkes M, Kang YJ. Changes in the gene expression associated with carbon tetrachloride-induced liver fibrosis persist after cessation of dosing in mice. Toxicological Sciences. 2004;79:404–410.

Pereira-Filho G, Ferreira C, Schwengber A, Marroni C, Zettler C, Marroni N. Role of N-acetylcysteine on fibrosis and oxidative stress in cirrhotic rats. Arq Gastroenterol. 2008;45:156–162.

Sari AW. Ekspresi protein sitoglobin pada hati tikus yang diinduksi karbon tetraklorida dengan perlindungan N-Asetil sistein [Tesis]. Jakarta: Universitas Indonesia; 2010.

Lemieux H, Bulteau AL, Friguet B, Tardif JC, Blier PU. Dietary fatty acids and oxidative stress in the heart mitochondria. Mitochondrion. 2011;11:97–103.

Sabitha P, Vasudevan DM, Kamath P. Effect of high fat diet without cholesterol supplementation on oxidative stress and lipid peroxidation in New Zealand white rabbits. J Atheroscler Thromb. 2010;17(2):213–218.




DOI: https://doi.org/10.32889/actabioina.v1i1.3

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