Intestinal Redox Status of Major Intracellular Thiols in a Rat Model of Chronic Alcohol Consumption

Abstract

Background: Alcohol consumption is associated with oxidative stress in multiple tissues in vivo, yet the effect of chronic alcohol intake on intestinal redox state has received little attention. In this study, we investigated the redox status of 2 major intracellular redox regulating couples: glutathione (GSH)/glutathione disulfide (GSSG) and cysteine (Cys)/cystine (CySS) in a rat model of chronic alcohol ingestion. Methods: Sprague-Dawley rats were fed the liquid Lieber-DeCarli diet consisting of 36% ethanol of total calories for 6 weeks. Control rats were pair-fed with an isocaloric, ethanol-free liquid diet. Defined mucosal samples from the jejunum, ileum, and colon were obtained and analyzed by high-performance liquid chromatography (HPLC) for GSH and Cys pool redox status. Mucosal free malondialdehyde (MDA) was measured as an indicator of lipid peroxidation. Results: In the ethanol-fed rats, Cys and mixed disulfide (GSH-Cys) were significantly decreased in all 3 segments of intestinal mucosa. Free MDA was increased in jejunal but not in ileal or colonic mucosa. Chronic ethanol ingestion significantly increased mucosal GSH concentration in association with a more reducing GSH/GSSG redox potential in the jejunum, but these indices were unchanged in the ileum. In the colon, chronic ethanol ingestion increased oxidant stress as suggested by decreased GSH and oxidized GSH/GSSG redox potential. Conclusions: Chronic alcohol intake differentially alters the mucosal redox status in proximal to distal intestinal segments in rats. Such changes may reflect different adaptability of these intestinal segments to the oxidative stress challenge induced by chronic ethanol ingestion.

Get full access to this article

View all access options for this article.

References

Guidot DM, Hart CM. Alcohol abuse and acute lung injury: epidemiology and pathophysiology of a recently recognized association.J Invest Med. 2005;53:235 -245.

Vendemiale G, Grattagliano I, Altomare E, et al. Mitochondrial oxidative damage and myocardial fibrosis in rats chronically intoxicated with moderate doses of ethanol. Toxicol Let. 2001 ;123:209 -216.

Altomare E, Grattagliano I, Vendemiale G, Palmieri V, Palasciano G. Acute ethanol administration induces oxidative changes in rat pancreatic tissue. Gut. 1996;38:742 -746.

Grattagliano I, Palmieri V, Vendemiale G, Portincasa P, Altomare E, Palasciano G. Chronic ethanol administration induces oxidative alterations and functional impairment of pancreatic mitochondria in the rat.Digestion. 1999;60:549 -553.

Fernandez-Checa JC, Kaplowitz N. The use of monochlorobimane to determine hepatic GSH levels and synthesis. Anal Biochem. 1990 ;190:212 -219.

Vendemiale G, Grattagliano I, Signorile A, Altomare E. Ethanol-induced changes of intracellular thiol compartmentation and protein redox status in the rat liver: effect of tauroursodeoxycholate. J Hepatol. 1998;28:46 -53.

Aydin S, Ozaras R, Uzun H, et al. N-acetylcysteine reduced the effect of ethanol on antioxidant system in rat plasma and brain tissue.Tohoku J Exp Med. 2002;198:71 -77.

Nordmann R, Ribiere C, Rouach H. Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues. Alcohol Alcoholism. 1990;25:231 -237.

Moghadasian MH, Godin DV. Ethanol-induced gastrointestinal damage: influence of endogenous antioxidant components and gender. Dig Dis Sci. 1996;41:791 -797.

10.

Shi MM, Kugelman A, Iwamoto T, Tian L, Forman HJ. Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells. J Biol Chem. 1994;269:26512 -26517.

11.

Diaz D, Krejsa CM, White CC, Keener CL, Farin FM, Kavanagh TJ. Tissue specific changes in the expression of glutamate-cysteine ligase mRNAs in mice exposed to methylmercury. Toxicol Let. 2001 ;122:119 -129.

12.

Victor BE, Schmidt KL, Smith GS, Miller TA. Protection against ethanol injury in the canine stomach: role of mucosal glutathione. Am J Physiol. 1991;261:G966 -G973.

13.

Kaur J. Chronic ethanol feeding affects intestinal mucus lipid composition and glycosylation in rats. Ann Nutr Metab. 2002 ;46:38 -44.

14.

Kaur M, Kaur J, Ojha S, Mahmood A. Ethanol effects on lipid peroxidation and glutathione-mediated defense in rat small intestine: role of dietary fats. Alcohol. 1998 ;15(1):65 -69.

15.

Bannai S. Induction of cystine and glutamate transport activity in human fibroblasts by diethyl maleate and other electrophilic agents. J Biol Chem. 1984 ;259(4):2435 -2440.

16.

Salaspuro M. Bacteriocolonic pathway for ethanol oxidation: characteristics and implications. Ann Med. 1996 ;28:195 -200.

17.

Brown L, Harris F, Guidot D. Chronic ethanol ingestion potentiates TNF-alpha mediated oxidative stress and apoptosis in rat type II cells.Am J Physiol. 2001;281:L377 -L386.

18.

Jones DP, Mody VC Jr, Carlson JL, Lynn MJ, Sternberg P Jr. Redox analysis of human plasma allows separation of pro-oxidant events of aging from decline in antioxidant defenses. Free Radic Biol Med. 2002 ;33:1290 -1300.

19.

Jonas CR, Puckett AB, Jones DP, et al. Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients. Am J Clin Nutr. 2000 ;72:181 -189.

20.

Inagaki-Ohara K, Takamura N, Yada S, et al. Radiation-induced crypt intestinal epithelial cell apoptosis in vivo involves both caspase-3-dependent and -independent pathways. Dig Dis Sci. 2002 ;47:2823 -2830.

21.

Preedy VR, Marway JS, Siddiq T, Ansari FA, Hashim IA, Peters TJ. Gastrointestinal protein turnover and alcohol misuse. Drug Alcohol Depend. 1993;34:1 -10.

22.

Souza HS, Elia CC, Braulio VB, et al. Effects of ethanol on gut-associated lymphoid tissues in a model of bacterial translocation: a possible role of apoptosis. Alcohol. 2003 ;30:183 -191.

23.

Fleming S, Toratani S, Shea-Donohue T, Kashiwabara Y, Vogel SN, Metcalf ES. Pro- and anti-inflammatory gene expression in the murine small intestine and liver after chronic exposure to alcohol. Alcohol Clin Exp Res. 2001;25:579 -589.

24.

Jones DP, Go YM, Anderson CL, Ziegler TR, Kinkade JM Jr, Kirlin WG. Cysteine/cystine couple is a newly recognized node in the circuitry for biologic redox signaling and control. FASEB J. 2004 ;18:1246 -1248.

25.

Cho CH, Pfeiffer CJ, Misra HP. Ethanol and the antioxidant defense in the gastrointestinal tract. Acta Physiol Hung. 1992 ;80:99 -105.

26.

Das SK, Vasudevan DM. Alcohol-induced oxidative stress. Life Sci. 2007;81:177 -187.

27.

Lutnicki K, Wrobel J, Ledwozyw A, Trebas-Pietras E. The effect of ethyl alcohol on peroxidation processes and activity of antioxidant enzymes in rat's gastric mucosa. Arch Vet Pol. 1992 ;32:117 -123.

28.

Amanvermez R, Tuncel OK, Demir S, Kefeli M, Bek Y, Celik C. Protective effects of cysteine, methionine and vitamin C on the stomach in chronically alcohol treated rats. J Appl Toxicol. 2008 ;28:591 -598.

29.

Visapaa JP, Tillonen J, Salaspuro M. Microbes and mucosa in the regulation of intracolonic acetaldehyde concentration during ethanol challenge. Alcohol Alcoholism. 2002 ;37:322 -326.