Protein Information

Name alcohol dehydrogenase (protein family or complex)
Synonyms ADH; alcohol dehydrogenase; alcohol dehydrogenases

Compound Information

Name cyanamide
CAS cyanamide

Reference List

PubMed Abstract RScore(About this table)
8843167 Svensson S, Lundsjo A, Cronholm T, Hoog JO: Aldehyde dismutase activity of human liver alcohol dehydrogenase. . FEBS Lett. 1996 Sep 30;394(2):217-20.

The class I beta1beta1 isozyme and the class II alcohol dehydrogenase showed moderate catalytic efficiencies for dismutase activity with lower kcat values, 60-75 min (-1). 4-Methylpyrazole, a potent class I ADH inhibitor, inhibited the class I dismutation completely, but cyanamide, an inhibitor of mitochondrial aldehyde dehydrogenase, did not affect the dismutation.
2(0,0,0,2) Details
3612528 Ghanayem BI, Burka LT, Matthews HB: Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases. J Pharmacol Exp Ther. 1987 Jul;242(1):222-31.

Pretreatment of rats with cyanamide (aldehyde dehydrogenase inhibitor) also significantly protected rats against BE-induced hematotoxicity and modified BE metabolism in a manner similar to that caused by pyrazole.
Treatment of rats with pyrazole (alcohol dehydrogenase inhibitor) protected rats against BE-induced hematotoxicity and inhibited BE metabolism to BAA.
2(0,0,0,2) Details
1632841 Aragon CM, Rogan F, Amit Z: Ethanol metabolism in rat brain homogenates by a catalase-H2O2 system. Biochem Pharmacol. 1992 Jul 7;44(1):93-8.


Homogenates of perfused brains of rats treated with 3-amino-1,2,4-triazole or cyanamide (another H2O2-dependent catalase blocker) also showed a dose-dependent reduction of the acetaldehyde obtained.
0(0,0,0,0) Details
2394940 Solomon LR, Crouch JY: delta-Aminolevulinic acid dehydratase in rat liver: studies on the effects of ethanol, acetaldehyde, and B6 vitamers. J Lab Clin Med. 1990 Aug;116(2):228-36.


Inactivation of ALAD by acetaldehyde was prevented by the metabolic inhibitor NaF but not by the aldehyde dehydrogenase inhibitor cyanamide.
0(0,0,0,0) Details
2499314 Heinstra PW, Geer BW, Seykens D, Langevin M: The metabolism of ethanol-derived acetaldehyde by alcohol dehydrogenase (EC 1.1.1.1) and aldehyde dehydrogenase (EC 1.2.1.3) in Drosophila melanogaster larvae. Biochem J. 1989 May 1;259(3):791-7.

The enzymes, however, showed different inhibition patterns with respect to pyrazole, cyanamide and disulphiram.
2(0,0,0,2) Details
11893554 Duan J, McFadden GE, Borgerding AJ, Norby FL, Ren BH, Ye G, Epstein PN, Ren J: Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1216-22.

Pretreatment with the ADH inhibitor 4-methylpyrazole (4-MP) or the aldehyde dehydrogenase inhibitor cyanamide prevented or augmented the ethanol-induced inhibition, respectively, in the ADH but not the FVB group.
2(0,0,0,2) Details
11835630 Burcham PC, Fontaine F: Extensive protein carbonylation precedes acrolein-mediated cell death in mouse hepatocytes. J Biochem Mol Toxicol. 2001;15(6):309-16.

Allyl alcohol hepatotoxicity is mediated by an alcohol dehydrogenase-derived biotranformation product, acrolein.
Conversely, cyanamide, an aldehyde dehydrogenase inhibitor, enhanced cytotoxicity and protein carbonylation.
2(0,0,0,2) Details
11033416 Srivastava S, Dixit BL, Cai J, Sharma S, Hurst HE, Bhatnagar A, Srivastava SK: Metabolism of lipid peroxidation product, 4-hydroxynonenal (HNE) in rat erythrocytes: role of aldose reductase. Free Radic Biol Med. 2000 Oct 1;29(7):642-51.


Inhibitors of aldehyde or alcohol dehydrogenase, i.e., cyanamide and 4-methyl pyrazole, had no effect on the formation of HNA and GS-DHN, indicating that these enzymes are not significant participants in the erythrocyte HNE metabolism.
0(0,0,0,0) Details
11981770 Clemens DL, Forman A, Jerrells TR, Sorrell MF, Tuma DJ: Relationship between acetaldehyde levels and cell survival in ethanol-metabolizing hepatoma cells. Hepatology. 2002 May;35(5):1196-204.

Furthermore, treatment of ethanol-metabolizing VA cells with the aldehyde dehydrogenase inhibitor, cyanamide, increased the levels of acetaldehyde and resulted in an additional reduction in cell number.
We have created a number of recombinant Hep G2 cell lines, designated VA cells, that constitutively express alcohol dehydrogenase.
2(0,0,0,2) Details
7840616 Hartley DP, Ruth JA, Petersen DR: The hepatocellular metabolism of 4-hydroxynonenal by alcohol dehydrogenase, aldehyde dehydrogenase, and glutathione S-transferase. Arch Biochem Biophys. 1995 Jan 10;316(1):197-205.

The presence of 4-methylpyrazole or cyanamide abolished formation of the reductive metabolite 1,4-dihydroxy-2-nonene or the oxidative metabolite 4-hydroxy-2-nonenoic acid in hepatocyte suspensions.
2(0,0,0,2) Details
4038270 Cronholm T: Incorporation of the 1-pro-R and 1-pro-S hydrogen atoms of ethanol in the reduction of acids in the liver of intact rats and in isolated hepatocytes. Biochem J. 1985 Jul 15;229(2):323-31.

Additions known to increase ethanol elimination, and cyanamide, which decreases it, had no marked effect on the 2H incorporation.
This indicates equilibration of the NADH bound to alcohol dehydrogenase with free NADH.
1(0,0,0,1) Details
3178876 Kera Y, Ohbora Y, Komura S: The metabolism of acetaldehyde and not acetaldehyde itself is responsible for in vivo ethanol-induced lipid peroxidation in rats. Biochem Pharmacol. 1988 Oct 1;37(19):3633-8.

The pretreatment with alcohol dehydrogenase (ADH) inhibitor, 4-methylpyrazole (1 mmol/kg) caused approximately 50% inhibition of the hepatic ADH activity and abolished this ethanol-induced lipid peroxidation.
The cyanamide treatment (15 mg/kg) effectively decreased 83% of the low Km and 70% of the high Km ALDH in the liver.
1(0,0,0,1) Details
9113267 Hartley DP, Petersen DR: Co-metabolism of ethanol, ethanol-derived acetaldehyde, and 4-hydroxynonenal in isolated rat hepatocytes. Alcohol Clin Exp Res. 1997 Apr;21(2):298-304.

To determine further if 4-HNE and ethanol are metabolized through the same metabolic pathways, cells were preincubated with either 4-methylpyrazole or cyanamide to inhibit alcohol dehydrogenase (E.C. 1.1.1.1.) and aldehyde dehydrogenase (E.C. 1.2.1.2.), respectively.
82(1,1,1,2) Details
8442754 Cronholm T: Ethanol metabolism in isolated hepatocytes. Biochem Pharmacol. 1993 Feb 9;45(3):553-8.

Effects of methylene blue, cyanamide and penicillamine on the redox state of the bound coenzyme and on the substrate exchange at alcohol dehydrogenase..
82(1,1,1,2) Details
3218384 Nanikawa R, Moriya F, Hashimoto Y: Experimental studies on the mechanism of ethanol formation in corpses. Z Rechtsmed. 1988;101(1):21-6.

Pyrazole, cyanamide, and disulfiram completely inhibited the production of ethanol.
When alcohol dehydrogenase (ADH) and reduced nicotinamide adenine dinucleotide (NADH) were added, ethanol production was slightly increased.
1(0,0,0,1) Details
9972923 Lee JY, Chung SM, Lee MY, Chung JH: Ethanol co-exposure increases lethality of allyl alcohol in male Sprague-Dawley rats. J Toxicol Environ Health A. 1999 Jan 22;56(2):121-30.


Since allyl alcohol and ethanol are both metabolized by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), ethanol could affect allyl-alcohol induced toxicity under in vivo coexposure conditions.
1(0,0,0,1) Details
8135858 Nikiforov AA, Ostretsova IB: Stimulatory effect of ethanol on weak organic acid uptake in rat renal tubules. Biochem Pharmacol. 1994 Mar 2;47(5):821-5.

The stimulation of fluorescein uptake by ethanol (20 mM) was abolished by an inhibitor of alcohol dehydrogenase (EC 1.1.1.1), pyrazole (1 mM), or an inhibitor of aldehyde dehydrogenase (EC 1.2.1.3), cyanamide (0.3 mM), suggesting that oxidation of ethanol mediated its effect on the uptake.
81(1,1,1,1) Details
9615272 Altomare E, Grattagliano I, Didonna D, Gentile A, Vendemiale G: Gastric and intestinal ethanol toxicity in the rat. Ital J Gastroenterol Hepatol. 1998 Feb;30(1):82-90.

Cimetidine and cyanamide inhibited by 50% the activity of alcohol dehydrogenase and by 80% aldehyde dehydrogenase, respectively, in the gastric and intestinal mucosa.
81(1,1,1,1) Details
2596853 Silva JM, O'Brien PJ: Allyl alcohol- and acrolein-induced toxicity in isolated rat hepatocytes. . Arch Biochem Biophys. 1989 Dec;275(2):551-8.

Incubation of isolated hepatocytes with allyl alcohol results in GSH depletion and subsequent cytotoxicity which is prevented by pyrazole, an inhibitor of alcohol dehydrogenase.
However, cytotoxicity of both allyl alcohol and acrolein was enhanced by the aldehyde dehydrogenase inhibitors cyanamide and disulfiram.
1(0,0,0,1) Details
11781286 Gukovskaya AS, Mouria M, Gukovsky I, Reyes CN, Kasho VN, Faller LD, Pandol SJ: Ethanol metabolism and transcription factor activation in pancreatic acinar cells in rats. Gastroenterology. 2002 Jan;122(1):106-18.

Ethanol decreased NF-kappa B binding activity in acinar cells, which was potentiated by cyanamide.
METHODS: We measured activities of fatty acid ethyl ester (FAEE) synthase and alcohol dehydrogenase (ADH), as well as accumulation of ethanol metabolites.
1(0,0,0,1) Details
3801056 Jaeschke H, Kleinwaechter C, Wendel A: The role of acrolein in allyl alcohol-induced lipid peroxidation and liver cell damage in mice. Biochem Pharmacol. 1987 Jan 1;36(1):51-7.

In vivo-inhibition of alcohol dehydrogenase by pyrazole or induction of aldehyde dehydrogenase by phenobarbital abolished AA-induced liver damage as well as glutathione depletion and lipid peroxidation, while inhibition of aldehyde dehydrogenase by cyanamide made a subtoxic dose of AA (0.60 mmol/kg) highly toxic.
32(0,1,1,2) Details
7894532 Pronko P, Zimatkin S, Kuzmich A: Effect of aldehyde dehydrogenase and alcohol dehydrogenase inhibitors and ethanol on blood and liver ketone bodies in the rat. Pol J Pharmacol. 1994 Sep-Oct;46(5):445-9.

The effects of the aldehyde dehydrogenase (ALDH) inhibitors: cyanamide (CY) and disulfiram (DS) and the alcohol dehydrogenase (ADH) inhibitor, pyrazole (PY) and the combination of these drugs with ethanol (ET, 3.5 g/kg, ip 6 h before decapitation) on the concentrations of rat blood and liver ketone bodies were studied.
32(0,1,1,2) Details
9632053 Nosova T, Jokelainen K, Kaihovaara P, Heine R, Jousimies-Somer H, Salaspuro M: Characteristics of aldehyde dehydrogenases of certain aerobic bacteria representing human colonic flora. Alcohol Alcohol. 1998 May-Jun;33(3):273-80.

The apparent Michaelis constant (Km) values for acetaldehyde were determined in crude extracts of five aerobic bacterial strains, alcohol dehydrogenase (ADH) and ALDH activities of these bacteria at conditions prevailing in the human large intestine after moderate drinking were then compared.
The effect of cyanamide, a potent inhibitor of mammalian ALDH, on bacterial ALDH activity was also studied.
1(0,0,0,1) Details
2272522 Rikans LE, Snowden CD, Moore DR: Influence of aging on ethanol and acetaldehyde oxidation in female rat liver. Gerontology. 1990;36(4):185-92.

Rates of ethanol metabolism by alcohol dehydrogenase, the microsomal ethanol oxidizing system (MEOS), and catalase were similar in liver preparations from young (4-5 months) and old (24-27 months) female Fischer 344 rats.
Results with the ALDH inhibitor cyanamide indicated that a decline in ALDH activity of this magnitude would not increase acute ethanol hepatotoxicity.
1(0,0,0,1) Details
17989515 Tambour S, Closon C, Tirelli E, Quertemont E: Effects of cyanamide and acetaldehyde accumulation on the locomotor stimulant and sedative effects of ethanol in mice. Behav Pharmacol. 2007 Dec;18(8):777-84.

Additionally, 4-methylpyrazole, an inhibitor of the enzyme alcohol dehydrogenase, prevented these effects of cyanamide.
31(0,1,1,1) Details
3620014 Spivak K, Aragon CM, Amit Z: Alterations in brain aldehyde dehydrogenase activity modify the locomotor effects produced by ethanol in rats. Alcohol Drug Res. 1987;7(5-6):481-91.

Concurrent administration with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide.
31(0,1,1,1) Details
1766365 Heinstra PW, Geer BW: Metabolic control analysis and enzyme variation: nutritional manipulation of the flux from ethanol to lipids in Drosophila. Mol Biol Evol. 1991 Sep;8(5):703-8.

The effect that variation in activities of the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) has on the flux from 14C-ethanol to lipids was examined in third-instar larvae of Drosophila melanogaster and D. simulans.
The activities of ADH and ALDH were also nutritionally manipulated by the inhibitor, cyanamide.
1(0,0,0,1) Details
12960514 Jamal M, Ameno K, Ameno S, Okada N, Ijiri I: In vivo study of salsolinol produced by a high concentration of acetaldehyde in the striatum and nucleus accumbens of free-moving rats. Alcohol Clin Exp Res. 2003 Aug;27(8 Suppl):79S-84S.

METHODS: After the insertion of a microdialysis probe, male Wistar rats (250-300 g) were treated with cyanamide (CY, a potent aldehyde dehydrogenase inhibitor) + ethanol (EtOH), CY + 4-methylpyrazole (4-MP, a strong alcohol dehydrogenase inhibitor) + EtOH, 4-MP + EtOH, CY, and 4-MP.
31(0,1,1,1) Details
3508430 Younes M, Strubelt O: Alcohol-induced hepatotoxicity: a role for oxygen free radicals. Free Radic Res Commun. 1987;3(1-5):19-26.

Inhibition of alcohol dehydrogenase by 4-methylpyrazole or of aldehyde dehydrogenase by cyanamide totally abolished ethanol hepatotoxicity despite of a severalfold increase in acetaldehyde concentration in the perfusate.
31(0,1,1,1) Details
8861782 Khan S, Sood C, O'Brien PJ: The involvement of cytochrome P4502E1 in 2-bromoethanol-induced hepatocyte cytotoxicity. Pharmacol Toxicol. 1996 Apr;78(4):241-8.

Furthermore, aldehyde dehydrogenase inhibitors-cyanamide or chloral hydrate increased 2-bromoethanol dependent hepatocyte susceptibility.
Alcohol dehydrogenase inhibitors, methyl pyrazole or dimethyl sulfoxide only partly prevented 2-bromoethanol induced GSH depletion, lipid peroxidation and cytotoxicity.
1(0,0,0,1) Details
2807159 Lin RC, Lumeng L: Further studies on the 37 kD liver protein-acetaldehyde adduct that forms in vivo during chronic alcohol ingestion. Hepatology. 1989 Nov;10(5):807-14.

When immunoblotted with anti-alcohol dehydrogenase and anti-aldehyde dehydrogenase antibodies, the alcohol dehydrogenase and aldehyde dehydrogenase bands in liver of alcohol-fed rats showed identical intensities before and after immunosorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Addition of cyanamide, an aldehyde dehydrogenase inhibitor, to the AIN'76 alcohol diet greatly increased the intensity of the 37-kD protein-acetaldehyde adduct band on electroimmunotransblot but did not produce other bands.
1(0,0,0,1) Details
10723960 Ijiri I: [Biological actions of acetaldehyde] . Nihon Hoigaku Zasshi. 1999 Nov;53(3):285-95.

After pretreatment with cyanamide (CY), a potent inhibitor of aldehyde dehydrogenase, or pyrazole (PY), a potent inhibitor of alcohol dehydrogenase, a 17% EtOH solution (0.4 g/kg) was administered into the jejunum segment, and 150 min after the administration of EtOH, the fluid from the segment was collected to determine its volume and EtOH concentration.
31(0,1,1,1) Details
11022051 Galli A, Pinaire J, Fischer M, Dorris R, Crabb DW: The transcriptional and DNA binding activity of peroxisome proliferator-activated receptor alpha is inhibited by ethanol metabolism. J Biol Chem. 2001 Jan 5;276(1):68-75.

This effect of ethanol was abolished by the alcohol dehydrogenase inhibitor 4-methylpyrazole and augmented by the aldehyde dehydrogenase inhibitor cyanamide, indicating that acetaldehyde was responsible for the action of ethanol.
31(0,1,1,1) Details
7010034 Sharkawi M: Inhibition of alcohol dehydrogenase by disulfiram; possible relation to the disulfiram-ethanol reaction. Life Sci. 1980 Nov 24;27(21):1939-45.

1(0,0,0,1) Details
9010546 Nosova T, Jokelainen K, Kaihovaara P, Jousimies-Somer H, Siitonen A, Heine R, Salaspuro M: Aldehyde dehydrogenase activity and acetate production by aerobic bacteria representing the normal flora of human large intestine. Alcohol Alcohol. 1996 Nov;31(6):555-64.

We have recently proposed the existence of a bacteriological pathway for ethanol oxidation, i.e. ethanol is oxidized by alcohol dehydrogenase of intestinal bacteria resulting in high intracolonic levels of reactive and toxic acetaldehyde.
In addition, aerobic bacteria metabolized acetaldehyde effectively in vitro and this could be inhibited by cyanamide in nearly half of the tested strains.
1(0,0,0,1) Details
3324799 Spivak K, Aragon CM, Amit Z: Alterations in brain aldehyde dehydrogenase activity modify ethanol-induced conditioned taste aversion. Alcohol Clin Exp Res. 1987 Dec;11(6):513-7.

Concurrent administration with 4-methylpyrazole (4MP), an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide.
31(0,1,1,1) Details
8394073 Mattia CJ, Adams JD Jr, Bondy SC: Free radical induction in the brain and liver by products of toluene catabolism. Biochem Pharmacol. 1993 Jul 6;46(1):103-10.

Pretreatment of rats in vivo with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, or sodium cyanamide, an aldehyde dehydrogenase inhibitor, prior to exposure to toluene, caused a significant decrease and increase, respectively, in toluene-stimulated rates of ROS generation in the CNS and liver.
31(0,1,1,1) Details
2312053 Lin RC, Fillenwarth MJ, Minter R, Lumeng L: Formation of the 37-kD protein-acetaldehyde adduct in primary cultured rat hepatocytes exposed to alcohol. Hepatology. 1990 Mar;11(3):401-7.

When cultured in hormone-enriched and trace metal-enriched Waymouth's medium, alcohol dehydrogenase activities in hepatocytes decreased only about 30% during 6 days of culture.
Although the maximal intensity was obtained at approximately 10 to 40 mmol/L ethanol, addition of cyanamide (an inhibitor of aldehyde dehydrogenase) further increased the intensity of this protein-acetaldehyde adduct band by more than twofold.
1(0,0,0,1) Details
8365577 Smialowicz RJ, Riddle MM, Williams WC: Methoxyacetaldehyde, an intermediate metabolite of 2-methoxyethanol, is immunosuppressive in the rat. Fundam Appl Toxicol. 1993 Jul;21(1):1-7.

Rats pretreated with the aldehyde dehydrogenase inhibitors disulfiram (2 mmol/kg) or cyanamide (0.48 mmol/kg) followed by oral dosing with ME (2.64 mmol/kg) resulted in suppressed PFC responses equivalent to the suppressed responses of rats dosed with ME alone.
In contrast, coadministration of the alcohol dehydrogenase inhibitor 4-methylpyrazole (1.2 mmol/kg) with ME or MEA blocked suppression of the PFC response following exposure to ME or MEA alone.
1(0,0,0,1) Details
19719790 Closon C, Didone V, Tirelli E, Quertemont E: Acetaldehyde and the hypothermic effects of ethanol in mice. Alcohol Clin Exp Res. 2009 Nov;33(11):2005-14. Epub 2009 Aug 31.

In experiments 3 and 4, mice received a combined pretreatment with cyanamide and the alcohol dehydrogenase (ADH) inhibitor 4-Methylpyrazole (10 mg/kg) before the injection of ethanol or acetaldehyde.
31(0,1,1,1) Details
6612730 Hillbom ME, Sarviharju MS, Lindros KO: Potentiation of ethanol toxicity by cyanamide in relation to acetaldehyde accumulation. Toxicol Appl Pharmacol. 1983 Aug;70(1):133-9.

Although administration of the alcohol dehydrogenase inhibitor, 4-methylpyrazole (4-MP, 10 mg/kg), prevented the accumulation of acetaldehyde, it only partly counteracted the effect of cyanamide on mortality.
31(0,1,1,1) Details
2886987 Penttila KE, Makinen J, Lindros KO: Allyl alcohol liver injury: suppression by ethanol and relation to transient glutathione depletion. Pharmacol Toxicol. 1987 May;60(5):340-4.

Inhibition of alcohol dehydrogenase by 4-methyl pyrazole completely counteracted these effects.
On the other hand, attempts to potentiate the toxicity of acrolein by the aldehyde dehydrogenase inhibitor cyanamide enhanced only the release of alanine aminotransferase.
1(0,0,0,1) Details
6347204 Dawson AG: Ethanol oxidation in systems containing soluble and mitochondrial fractions of rat liver. Biochem Pharmacol. 1983 Jul 15;32(14):2157-65.

The rate of ethanol oxidation in these systems was much lower than the measured maximum activity of alcohol dehydrogenase (ADH) and it was concluded that ADH was inhibited by the accumulated acetaldehyde.
Cyanamide, an inhibitor of mitochondrial ALDH, blocked the stimulatory effect of mitochondria on ethanol oxidation.
1(0,0,0,1) Details
8453736 Siddiq T, Richardson PJ, Mitchell WD, Teare J, Preedy VR: Ethanol-induced inhibition of ventricular protein synthesis in vivo and the possible role of acetaldehyde. Cell Biochem Funct. 1993 Mar;11(1):45-54.

Two metabolic inhibitors of ethanol metabolism were also used namely 4-methylpyrazole (alcohol dehydrogenase inhibitor) and cyanamide (acetaldehyde dehydrogenase inhibitor) which in ethanol-dosed rats have been shown to either decrease or increase acetaldehyde formation, respectively.
31(0,1,1,1) Details
6434593 Perez HD, Roll FJ, Bissell DM, Shak S, Goldstein IM: Production of chemotactic activity for polymorphonuclear leukocytes by cultured rat hepatocytes exposed to ethanol. J Clin Invest. 1984 Oct;74(4):1350-7.

It was undetectable in the absence of ethanol and was reduced in the presence of either the alcohol dehydrogenase inhibitor, 4-methylpyrazole, or the acetaldehyde dehydrogenase inhibitor, cyanamide.
31(0,1,1,1) Details
2264608 Lin RC, Lumeng L: Formation of the 37KD protein-acetaldehyde adduct in liver during alcohol treatment is dependent on alcohol dehydrogenase activity. Alcohol Clin Exp Res. 1990 Oct;14(5):766-70.

In this report, we have examined the effects of pyrazole (an ADH inhibitor) and cyanamide (an aldehyde dehydrogenase inhibitor) on the formation of the 37KD liver protein-AA in vivo and in vitro.
1(0,0,0,1) Details
8986222 Fujimiya T, Li YJ, Uemura K, Ohbora Y, Komura S: Noncompetitive-like inhibition of ethanol elimination by cyanamide treatment: pharmacokinetic study. Alcohol Clin Exp Res. 1996 Dec;20(9 Suppl):278A-283A.

The product, or competitive, inhibition of alcohol dehydrogenase by acetaldehyde had been reported in enzymological study.
1(0,0,0,1) Details
18324412 Halaly T, Pang X, Batikoff T, Crane O, Keren A, Venkateswari J, Ogrodovitch A, Sadka A, Lavee S, Or E: Similar mechanisms might be triggered by alternative external stimuli that induce dormancy release in grape buds. Planta. 2008 Jun;228(1):79-88. Epub 2008 Mar 7.

We compared the effects of heat shock (HS) and hydrogen cyanamide (HC) and demonstrated that HS leads to earlier and higher bud-break levels.
Changes in transcript levels of catalase, alcohol dehydrogenase and pyruvate decarboxylase were induced following both treatments.
1(0,0,0,1) Details
16540368 Gyamfi MA, Wan YJ: The effect of ethanol, ethanol metabolizing enzyme inhibitors, and Vitamin E on regulating glutathione, glutathione S-transferase, and S-adenosylmethionine in mouse primary hepatocyte. Hepatol Res. 2006 May;35(1):53-61. Epub 2006 Mar 15.

Lipid peroxidation (LPO), assessed by the thiobarbituric acid assay, increased to 221% of control by ethanol and was potentiated by cyanamide, an aldehyde dehydrogenase inhibitor.
The changes in LPO, cytosolic GST activity, GSH levels and SAMe/SAH ratio in ethanol exposed hepatocytes were completely or partially reversed by either Vitamin E or 4-methylpyrazole, an alcohol dehydrogenase (ADH) inhibitor.
1(0,0,0,1) Details
17597213 Jamal M, Ameno K, Uekita I, Kumihashi M, Wang W, Ijiri I: Catalase mediates acetaldehyde formation in the striatum of free-moving rats. Neurotoxicology. 2007 Nov;28(6):1245-8. Epub 2007 May 13.

Rats received intraperitoneal EtOH (1g/kg) alone or in combination with 4-methylpyrazole (MP, 82 mg/kg, an alcohol dehydrogenase inhibitor), and/or catalase inhibitor sodium azide (AZ, 10mg/kg) or 3-amino-1,2,4-triazole (AT, 1g/kg), and/or cyanamide (CY, 50mg/kg, an aldehyde dehydrogenase inhibitor).
31(0,1,1,1) Details
13861343 ANDO H, FUWA I: Effects of cyanamide on alcohol dehydrogenase and aldehyde dehydrogenase. J Chromatogr. 1961 Nov;50:416-8.
6(0,0,1,1) Details
6861004 Loomis CW, Brien JF: Specificity of hepatic aldehyde dehydrogenase inhibition by calcium carbimide (calcium cyanamide) in the rat. Can J Physiol Pharmacol. 1983 Apr;61(4):431-5.

0(0,0,0,0) Details
18317950 Vary TC, Lang CH: Differential phosphorylation of translation initiation regulators 4EBP1, S6k1, and Erk 1/2 following inhibition of alcohol metabolism in mouse heart. Cardiovasc Toxicol. 2008 Mar;8(1):23-32. Epub 2008 Mar 4.


Pretreatment with cyanamide, an inhibitor of aldehyde dehydrogenase, did not attenuate the ethanol-induced decrease in phosphorylation S6k1 (Thr (389)), but partially prevented the ethanol-induced lowering of 4EBP1 phosphorylation.
0(0,0,0,0) Details
8707122 Altomare E, Grattagliano I, Vendemiale G, Palmieri V, Palasciano G: Acute ethanol administration induces oxidative changes in rat pancreatic tissue. Gut. 1996 May;38(5):742-6.


Pretreatment with cyanamide (an inhibitor of aldehyde dehydrogenase) but not with 4-methylpyrazole (an alcohol dehydrogenase inhibitor) caused higher production of GSSG and MDA.
0(0,0,0,0) Details
7646056 Clemens DL, Halgard CM, Miles RR, Sorrell MF, Tuma DJ: Establishment of a recombinant hepatic cell line stably expressing alcohol dehydrogenase. Arch Biochem Biophys. 1995 Aug 20;321(2):311-8.

Furthermore, the level of acetaldehyde produced during ethanol oxidation was augmented by cyanamide, an inhibitor of acetaldehyde oxidation, while the ability of these cells to metabolize ethanol was inhibited by pyrazole, an inhibitor of alcohol dehydrogenase.
6(0,0,0,6) Details
4038269 Cronholm T: Hydrogen transfer between ethanol molecules during oxidoreduction in vivo. Biochem J. 1985 Jul 15;229(2):315-22.

In cyanamide-treated rats, the elimination of ethanol was slow but the rates in the oxidoreduction were high, indicating more complete rate-limitation by the oxidation of acetaldehyde.
Rates of exchange catalysed by alcohol dehydrogenase were determined in vivo in order to find rate-limiting steps in ethanol metabolism.
3(0,0,0,3) Details
14615007 Moncada C, Fuentes N, Lladser A, Encina G, Sapag A, Karahanian E, Israel Y: Use of an "acetaldehyde clamp" in the determination of low-KM aldehyde dehydrogenase activity in H4-II-E-C3 rat hepatoma cells. Alcohol. 2003 Aug-Oct;31(1-2):19-24.

We showed that (1) acetate production is linear for 120 min, (2) addition of 160 microM cyanamide to the culture medium leads to a 75%-80% reduction of acetate generated, and (3) ALDH2 activity is dependent on cell-to-cell contact and increases after cells reach confluence.
The clamp is attained by addition of excess yeast alcohol dehydrogenase, 14C-ethanol, and oxidized form of nicotinamide adenine dinucleotide (NAD (+)) to the hepatoma cell culture medium.
2(0,0,0,2) Details
2932116 Ryle PR, Chakraborty J, Thomson AD: The roles of the hepatocellular redox state and the hepatic acetaldehyde concentration in determining the ethanol elimination rate in fasted rats. Biochem Pharmacol. 1985 Oct 1;34(19):3577-83.

Pretreatment of animals with the aldehyde dehydrogenase inhibitor, cyanamide (1 mg/kg or 15 mg/kg p.o. one hour before ethanol), caused increases of up to 23-fold in the hepatic acetaldehyde level, without influencing the cytosolic NAD+:NADH ratio in ethanol dosed rats, while significantly reducing the ethanol elimination rate by up to 44%, compared with controls.
These results suggest that ethanol oxidation by cytosolic alcohol dehydrogenase may be regulated in part by the hepatic acetaldehyde concentration achieved during ethanol metabolism rather than NADH reoxidation, either to supply NAD for the dehydrogenase, or to reduce inhibition of the enzyme by NADH, being a rate-limiting factor in ethanol metabolism in fasted rats.
1(0,0,0,1) Details
6884350 Muller A, Sies H: Ethane release during metabolism of aldehydes and monoamines in perfused rat liver. Eur J Biochem. 1983 Aug 15;134(3):599-602.

Compounds which metabolically generate aldehydes such as monoamines (benzylamine, phenylethylamine) as substrates for monoamine oxidase or ethanol as substrate for alcohol dehydrogenase [A.
Results obtained with inhibitors of hepatic aldehyde metabolism (pargyline or cyanamide) or of monamine oxidase (pargyline or tranylcypromine) suggest that metabolism of the aldehydes is required for ethane production.
1(0,0,0,1) Details
3606666 Carmichael FJ, Israel Y, Saldivia V, Giles HG, Meggiorini S, Orrego H: Blood acetaldehyde and the ethanol-induced increase in splanchnic circulation. Biochem Pharmacol. 1987 Aug 15;36(16):2673-8.

As earlier studies have indicated that this effect is maximal at concentrations of ethanol that saturate the alcohol dehydrogenase (ADH) system and is blocked by the ADH inhibitor 4-methylpyrazol, we investigated the possible role of acetaldehyde, a product in the ADH reaction, as a mediator of this effect.
In the first series of experiments it was shown that, contrary to expectations, cyanamide administration prior to alcohol suppressed fully the effect of ethanol on portal blood flow without altering it in the absence of ethanol [ethanol = 69.5 +/- 5.6; ethanol + cyanamide 42.9 +/- 2.4; control = 43.0 +/- 3.0; cyanamide = 55.1 +/- 3.7 ml X min-1 X (kg body wt)-1].
1(0,0,0,1) Details
12394292 Kumar V, Silvis C, Nystrom G, Deshpande N, Vary TC, Frost RA, Lang CH: Alcohol-induced increases in insulin-like growth factor binding protein-1 are partially mediated by TNF. Alcohol Clin Exp Res. 2002 Oct;26(10):1574-83.

Separate groups of rats were also pretreated with 4-methylpyrazole (4-MP; alcohol dehydrogenase inhibitor), cyanamide (inhibitor of acetaldehyde metabolism), RU486 (glucocorticoid receptor antagonist) or the tumor necrosis factor (TNF) antagonist (TNF (BP)) prior to EtOH administration.
Separate groups of rats were also pretreated with 4-methylpyrazole (4-MP; alcohol dehydrogenase inhibitor), cyanamide (inhibitor of acetaldehyde metabolism), RU486 (glucocorticoid receptor antagonist) or the tumor necrosis factor (TNF) antagonist (TNF (BP)) prior to EtOH administration.
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12036955 You M, Fischer M, Deeg MA, Crabb DW: Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). J Biol Chem. 2002 Aug 9;277(32):29342-7. Epub 2002 May 29.

This effect is likely mediated by acetaldehyde, because the effect was only seen in cell lines expressing alcohol dehydrogenase, and inhibition of ethanol oxidation by 4-methylpyrazole blocked the effect in the hepatoma cells.
Furthermore, the aldehyde dehydrogenase inhibitor cyanamide enhanced the effect of ethanol in the hepatoma cells.
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1845547 Lin RC, Lumeng L: Formation of the 37KD liver protein-acetaldehyde adduct in vivo and in vitro. Alcohol Alcohol Suppl. 1991;1:265-9.


However, under certain circumstances e.g. when fed an alcohol-containing liquid diet supplemented with cyanamide (an aldehyde dehydrogenase inhibitor that raises blood acetaldehyde concentrations), this 37KD protein-acetaldehyde adduct (protein-AA) becomes incorporated into liver plasma membranes.
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3702591 Guerri C, Sanchis R: Alcohol and acetaldehyde in rat's milk following ethanol administration. Life Sci. 1986 Apr 28;38(17):1543-56.


The time course of ethanol and acetaldehyde concentration in blood and milk were determined in normal lactating rats after cyanamide (40 mg/kg) and ethanol administration (2 or 4 g/kg).
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6353979 Kupari M, Lindros K, Hillbom M, Heikkila J, Ylikahri R: Cardiovascular effects of acetaldehyde accumulation after ethanol ingestion: their modification by beta-adrenergic blockade and alcohol dehydrogenase inhibition. Alcohol Clin Exp Res. 1983 Summer;7(3):283-8.

Left ventricular function was examined by echocardiography and systolic time intervals in nine healthy male volunteers, who ingested ethanol 0.35 g/kg 4 hr after a 50-mg peroral dose of calcium cyanamide, an aldehyde dehydrogenase inhibitor.
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3426694 Vind C, Grunnet N: Rate determining factors of ethanol oxidation in hepatocytes from starved and fed rats: effect of acetaldehyde concentration on the rate of NADH oxidation catalyzed by alcohol dehydrogenase. Alcohol Alcohol Suppl. 1987;1:295-9.

The concentration of the substrates of the two dehydrogenases were varied by addition of fructose and cyanamide.
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7030108 Lindros KO, Stowell A, Pikkarainen P, Salaspuro M: The disulfiram (Antabuse)-Alcohol reaction in male alcoholics: its efficient management by 4-methylpyrazole. Alcohol Clin Exp Res. 1981 Fall;5(4):528-30.


4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, rapidly abolished the accumulation of acetaldehyde following alcohol ingestion both in volunteers pretreated with the Antabuse analog calcium carbimide and in an antabuse-treated alcoholic. 4-MP also attenuated other typical symptoms, including facial flushing and tachycardia, thus suggesting its usefulness in the acute treatment of severe disulfiram-alcohol reactions.
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12711651 Jamal M, Ameno K, Kubota T, Ameno S, Zhang X, Kumihashi M, Ijiri I: In vivo formation of salsolinol induced by high acetaldehyde concentration in rat striatum employing microdialysis. Alcohol Alcohol. 2003 May-Jun;38(3):197-201.

AIMS: The in vivo formation of salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquionoline), an endogeneous condensation product of dopamine (DA) with acetaldehyde (AcH), was examined following the administration of cyanamide (CY) plus ethanol (EtOH) using microdialysis-high-performance liquid chromatography with electrochemical detection.
METHODS: After the insertion of a microdialysis probe into the striatum, rats were treated with CY (a potent inhibitor of aldehyde dehydrogenase, 50 mg/kg), 4-methylpyrazole (4-MP, a strong inhibitor of alcohol dehydrogenase, 82 mg/kg), and CY + 4-MP, followed 1 h later by EtOH (1 g/kg), CY and 4-MP only by intraperitoneal administration.
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9794917 Bailey SM, Cunningham CC: Acute and chronic ethanol increases reactive oxygen species generation and decreases viability in fresh, isolated rat hepatocytes. Hepatology. 1998 Nov;28(5):1318-26.

Acute ethanol exposure stimulated ROS production, increased the cellular NADH/NAD+ ratio, and decreased hepatocyte viability slightly, which was prevented by pretreatment with 4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase.
Incubation with pyruvate, an NADH-oxidizing compound, and cyanamide, an inhibitor of aldehyde dehydrogenase, significantly decreased ROS levels in acute ethanol-treated hepatocytes.
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1443429 Gill K, Menez JF, Lucas D, Deitrich RA: Enzymatic production of acetaldehyde from ethanol in rat brain tissue. Alcohol Clin Exp Res. 1992 Oct;16(5):910-5.


On the other hand, treatment with the catalase inhibitors sodium azide, cyanamide, or 3-amino-1,2,4-triazole blocked the production of AcHO while the addition of exogenous peroxide or a peroxide-generating system enhanced the production of AcHO.
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8032311 Fujita M, Sano M, Yoshino K, Tomita I: Effects of aldehyde dehydrogenase and glutathione on the degradation of (E)-4-hydroxy-2-nonenal and N-hexanal in rat liver. Biochem Mol Biol Int. 1994 Mar;32(3):429-34.


When lipid peroxidation was induced by t-butyl hydroperoxide, the ratio of HA to 4HN production in the liver of rats pretreated with the ALDH inhibitor, cyanamide (100 mg/kg, i.p.) was higher than that in controls, whereas the ratio was lower in the liver of rats pretreated with the glutathione-depleting agent, phorone (250 mg/kg, i.p.).
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