Chitooligosaccharides (COS), a kind of oligosaccharide made from chitin or chitosan, have been used a popular remedy for hangovers. In this study we investigated the in vitro effect of COS lactate salt on ethanol-induced cytotoxicity and the in vivo effect of short-term COS lactate salt feeding on ethanol-induced hangover. Pretreatment of HepG2 cells with COS lactate salt significantly reduced ethanol-induced cytotoxicity and suppressed generation of reactive oxygen species. In addition, COS lactate salt dose-dependently increased acetaldehyde dehydrogenase (ALDH) activity in vitro and reversed the ALDH inhibition induced by daidzin. Furthermore, oral administration of COS lactate salt (200 mg/kg) for 5 days significantly decreased the blood levels of alcohol and acetaldehyde in ethanol-treated mice. It was also demonstrated that hepatic mitochondrial ALDH activity was significantly increased in COS lactate salt-treated mice. Taken together, these findings indicate that COS lactate salt may have efficacy for the management of alcoholic hangovers.
PolavarapuR, SpitzDR, SimJE, FollansbeeMH, OberleyLW, RahemtullaA, NanjiAA. Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology, 1998; 27:1317–1323.
3.
TumaDJ, ThieleGM, XuD, KlassenLW, SorrellMF. Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration. Hepatology, 1996; 23:872–880.
4.
EkströmG, Ingelman-SundbergM. Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450IIE1)Biochem Pharmacol, 1989; 38:1313–1319.
5.
BaileySM, PietschEC, CunninghamCC. Ethanol stimulates the production of reactive oxygen species at mitochondrial complexes I and III. Free Radic Biol Med, 1999; 27:891–900.
6.
WuD, CederbaumAI. Ethanol cytotoxicity to a transfected HepG2 cell line expressing human cytochrome P4502E1. J Biol Chem, 1996; 271:23914–23919.
7.
Garcia-RuizC, MoralesA, ColellA, BallestaA, RodésJ, KaplowitzN, Fernández-ChecaJC. Feeding S-adenosyl-l-methionine attenuates both ethanol-induced depletion of mitochondrial glutathione and mitochondrial dysfunction in periportal and perivenous rat hepatocytes. Hepatology, 1995; 21:207–214.
AgarwalDP, GoeddeHW. Human aldehyde dehydrogenase: their role in alcoholism. Alcohol, 1989; 6:517–523.
16.
CrabbDW, MatsumotoM, ChangD, YouM. Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc, 2004; 63:49–63.
17.
AibaSI. Preparation of N-acetyl chitoologosaccharides by hydrolysis of chitosan with chitinase followed by N-acetylation. Carbohydr Res, 1994; 265:323–328.
18.
HiranoS, TsuchidaH, NagaoN. N-acetylation in chitosan and the rate of its enzymic hydrolysis. Biomaterials, 1989; 10:574–576.
19.
ChenAS, TaguchiT, SakaiK, MatahiraY, WangMW, MiwaI. Effect of chitobiose and chitotriose on carbon tetrachloride-induced acute hepatotoxicity in rats. Biol Pharm Bull, 2005; 28:1971–1973.
20.
KimSJ, KangSY, ParkSL, ShinTK, KoYH. Effects of chitooligosaccharides on liver function in the mouse. Korean J Food Sci Technol, 1998; 30:693–696.
21.
LaBelCP, IschiopoulosH, BondySC. Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation an oxidative stress. Chem Res Toxicol, 1992; 5:227–231.
22.
BostianKA, BettsGF. Kinetics and reaction mechanism of potassium-activated aldehyde dehydrogenase from Saccharomyces cerevisiae. Biochem J, 1978; 173:787–798.
23.
BoledaMD, JuliaP, MorenoA, ParesX. Role of extrahepatic alcohol dehydrogenase in rat ethanol metabolism. Arch Biochem Biophys, 1989; 274:74–81.
LeeSI, KimHJ, BooYC. Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells. Phytother Res, 2008; 22:669–674.
26.
BanysP. The clinical use of disulfiram (Antabuse): a review. J Psychoactive Drugs, 1988; 20:243–261.
27.
KeungWM, ValleeBL. Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. Proc Natl Acad Sci USA, 1993; 90:1247–1251.
28.
SuzukiK, MikamiT, OkawaY, TokoroA, SuzukiS, SuzukiM. Antitumor effect of hexa-N-acetylchitohexaose and chitohexaose. Carbohydr Res, 1986; 151:403–408.
29.
ChoiBK, KimKY, YooYJ, OhSJ, ChoiJH, KimCY. In vitro antimicrobial activity of a chitooligosaccharide mixture against Actinobacillus actinomycetemcomitans and Streptococcus mutans. Int J Antimicrobi Agents, 2001; 18:553–557.
30.
LiuB, LiuWS, HanBO, SunYY. Antidiabetic effects of chitooligosaccharides on pancreatic islet cells in streptozotocin-induced diabetic rats. World J Gastroenterl, 2007; 13:725–731.
31.
XueC, YuG, HirataT, TeraoJ, LinH. Antioxidative activities of several marine polysaccharides evaluated in a phosphatidylcholine-liposomal suspension and organic solvents. Biosci Biotechnol.Biochem, 1998; 62:206–209.
CiesielskaAS, SzerszenMK. Protective effects of betulin and betulinic acid against ethanol-induced cytotoxicity in HepG2 cells. Pharmacol Rep, 2005; 57:588–595.
34.
KimBY, GuiZG, LeeSR, KimSJ, KangHK, LeeYK, ParkDB. Effects of Asparagus officinalis extracts on liver cell toxicity and ethanol metabolism. J Food Sci, 2009; 74:H204–H208.
35.
YangES, LeeJH, ParkJW. Ethanol induces peroxynitrite-mediated toxicity through inactivation of NADP+-dependent isocitrate dehydrogenase and superoxide dismutase. Biochimie, 2008; 90:1316–1324.
36.
LeeSI, KimHJ, BooYC. Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells. Phytother Res, 2008; 22:669–674.
37.
MendisE, KimMM, RajapakseN, KimSK. An in vitro cellular analysis of the radical scavenging efficacy of chitooligosaccharides. Life Sci, 2007; 80:2118–2127.
38.
AlbanoE. Free radicals and alcohol-induced liver injury. Ethanol and the Liver. ShermanCD, PreedyVR, WatsonRR. Taylor and Francis: London, 2002; 153–190.
39.
IimuroY, BradfordBU, YamashinaS, RusynI, NakagamiM, EnomotoN, KonoH, FreyW, FormanD, BrennerD, ThurmanRG. The glutathione precursor l-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat. Hepatology, 2000; 31:391–398.
40.
RonisMJJ, ButuraA, SampeyBP, PriorRL, KorourianS, AlbanoE, Ingelman-SundbergM, PetersenDR, BadgerTM. Effects of N-acetyl cysteine on ethanol-induced hepatotoxicity in rats fed via total enteral nutrition. Free Radic Biol Med, 2005; 36:616–630.
41.
GoeddeHW, AgarwalDP. Pharmacogenetics of aldehyde dehydrogenase (ALDH)Pharmacol Ther, 1990; 45:345–371.
42.
SidhuRS, BlairAH. The action of chelating agents on human liver aldehyde dehydrogenase. Biochem J, 1975; 151:443–445.
43.
KeungWM, ValleeBL. Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehyrogenase. Proc Natl Acad Sci USA, 1993; 90:1247–1251.
44.
CantóC, Gerhart-HinesZ, FeigeJN, MagougeM, NoriegaL, MilneJC, ElliottPJ, PuigserverP, AuwerxJ. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature, 2009; 458:1056–1060.
KlyosovAA, RashkovetskyL, TahirMK, KeungWM. Possible role of liver cytosolic and mitochondrial aldehyde dehydrogenases in acetaldehyde metabolism. Biochemistry, 1996; 35:4445–4456.
47.
HaradaS, AgarwalDP, GoeddeHW. Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese. Lancet, 1981; 2:982.
48.
RookeN, LiDJ, LiJ, KeungWM. The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin. J Med Chem, 2000; 43:4169–4179.
49.
KeungWM, KlyosovAA, ValleeBL. Daidzin inhibits mitochondrial aldehyde dehydrogenase and suppresses ethanol intake of Syrian golden hamsters. Proc Natl Acad Sci USA, 1997; 94:1675–1679.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
