Abstract：
:Previous studies have reported that cimetidine, an H2-receptor antagonist used to treat gastric and duodenal ulcers, can inhibit alcohol dehydrogenases (ADHs) and ethanol metabolism. Human alcohol dehydrogenases and aldehyde dehydrogenases (ALDHs), the principal enzymes responsible for metabolism of ethanol, are complex enzyme families that exhibit functional polymorphisms among ethnic groups and distinct tissue distributions. We investigated the inhibition by cimetidine of alcohol oxidation by recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and aldehyde oxidation by ALDH1A1 and ALDH2 at pH 7.5 and a cytosolic NAD(+) concentration. Cimetidine acted as competitive or noncompetitive inhibitors for the ADH and ALDH isozymes/allozymes with near mM inhibition constants. The metabolic interactions between cimetidine and ethanol/acetaldehyde were assessed by computer simulation using the inhibition equations and the determined kinetic constants. At therapeutic drug levels (0.015 mM) and physiologically relevant concentrations of ethanol (10 mM) and acetaldehyde (10 μM) in target tissues, cimetidine could weakly inhibit (<5%) the activities of ADH1B2 and ADH1B3 in liver, ADH2 in liver and small intestine, ADH4 in stomach, and ALDH1A1 in the three tissues, but not significantly affect ADH1A, ADH1B1, ADH1C1/2, or ALDH2. At higher drug levels, which may accumulate in cells (0.2 mM), the activities of the weakly-inhibited enzymes may be decreased more significantly. The quantitative effects of cimetidine on metabolism of ethanol and other physiological substrates of ADHs need further investigation.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Lai CL,Li YP,Liu CM,Hsieh HS,Yin SJdoi
10.1016/j.cbi.2012.11.016subject
Has Abstractpub_date
2013-02-25 00:00:00pages
275-82issue
1-3eissn
0009-2797issn
1872-7786pii
S0009-2797(12)00260-8journal_volume
202pub_type
杂志文章abstract：:We had previously reported that the carcinogen, beta-propiolactone (BPL) reacted in vitro with histones in whole mouse skin chromatin and that among the histone classes BPL was preferentially bound to the lysine-rich histones H1 and H1 degrees. In order to determine if in vitro reaction of BPL with calf thymus histone...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(76)90137-x
更新日期：1976-12-01 00:00:00
abstract：:A model is presented which correlates the survival of normal human fibroblasts (NF) after exposure to N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) with the rate of excision of carcinogen residues bound to DNA. Measurements of the rate of excision of carcinogen residues suggest that this is a first-order process with 37...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(82)90005-9
更新日期：1982-03-01 00:00:00
abstract：:The molecular biology and enzymology of aldehyde dehydrogenase (ALDH) have been extensively investigated. However, most of the studies have been confined to the mammalian forms, while the sub-mammalian vertebrate ALDHs are relatively unexplored. In the present investigation, an ALDH was purified from the hepatopancrea...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(00)00231-3
更新日期：2001-01-30 00:00:00
abstract：:Current regulatory practices for chemical carcinogens were established when scientific understanding of the molecular mechanisms of chemical carcinogenesis was in its infancy. Initial discovery that DNA mutation was the root of cancer led quickly to regulatory processes that assumed such a simple relationship could be...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2019.01.025
更新日期：2019-03-01 00:00:00
abstract：:Intraperitoneal administration of chloroquine, primaquine and quinacrine to rats resulted in inhibition of the hepatic microsomal mixed-function oxidases. The N-demethylation of benzphetamine (cytochrome P-450) was inhibited by chloroquine only while the O-deethylation of ethoxyresorufin (cytochrome P-448) was inhibit...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(84)90154-6
更新日期：1984-10-01 00:00:00
abstract：:The relationship between dimethylnitrosamine (DMN) demethylase activity and DMN-induced mutagenesis was investigated in Drosophila melanogaster. The activity of DMN-demethylase was at least 10-fold greater in the Hikone-R strain than in three other Drosophila strains. However, the sex-linked recessive lethal (SLRL) mu...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(83)90006-6
更新日期：1983-08-15 00:00:00
abstract：:Formic acid is a common organic acid used in many industrial processes. There is a paucity of research on the direct toxicity of formic acid and how it might affect the cardiovascular system. This study aimed to understand the effect of formic acid on vascular tension in an animal model and the underlying mechanism. R...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.06.023
更新日期：2019-08-25 00:00:00
abstract：:Within the alpha/beta hydrolase fold superfamily of proteins, the COesterase group (carboxylesterase type B, block C, cholinesterases …) diverged from the other groups through simultaneous integration of an N-terminal, first disulfide bond and a significant increase in the protein mean size. This first disulfide bond ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.05.016
更新日期：2019-08-01 00:00:00
abstract：:Due to its ability to inhibit the blood platelet PGHS-1, acetylsalicylic acid (ASA, Aspirin(®)) is widely used as a preventive agent in atherothrombotic diseases. However, its beneficial effects seem to be lower in diabetic patients, suggesting that protein glycation may impair effective ASA-mediated acetylation proce...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.04.021
更新日期：2016-06-25 00:00:00
abstract：:The organ specificity of tris(2,3-dibromopropyl)phosphate(Tris-BP)-induced DNA damage was investigated in the rat 2 h after a single i.p. injection of 350 mumol/kg. Extensive DNA damage, measured with the alkaline elution method, was found in the kidney, liver and small intestine. Less, but significant DNA damage was ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(92)90110-7
更新日期：1992-04-15 00:00:00
abstract：:The effects of benzoflavones on skin tumor initiation by polycyclic hydrocarbons and epidermal aryl hydrocarbon hydroxylase were investigated. 7,8-Benzoflavone (7,8-BF) was found to be a potent inhibitor of the inhibition of skin tumors by 3-methylcholanthrene (MC) as well as 7,12-dimethylbenz(a)anthracene (DMBA). 5,6...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(77)90093-x
更新日期：1977-06-01 00:00:00
abstract：:This study investigated the spectral interactions of hepatic microsomal cytochrome p450 (CYP) enzymes with four symmetrical polychlorinated biphenyls (PCBs): 2,2',4,4'-tetrachlorobiphenyl (PCB 47); 2,2',5,5'-tetrachlorobiphenyl (PCB 52); 2,2',6,6'-tetrachlorobiphenyl (PCB 54); and 3,3',4,4'-tetrachlorobiphenyl (PCB 77...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2003.09.003
更新日期：2003-12-15 00:00:00
abstract：:4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) has been identified as one of the strongest nitrosamine carcinogens in tobacco products in all species tested. Carbonyl reduction to 4-methylnitrosamino-1-(3-pyridyl)-1-butanol (NNAL) followed by glucuronosylation is considered to be the main detoxification pathway in...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(00)00304-5
更新日期：2001-01-30 00:00:00
abstract：:There is growing interest in studying the toxicity and health risk of exposure to multi-pollutant mixtures found in ambient air, and the U.S. Environmental Protection Agency (EPA) is moving towards setting standards for these types of mixtures. Additionally, the Health Effects Institute's strategic plan aims to develo...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.06.026
更新日期：2014-09-05 00:00:00
abstract：:The degradation in alkali of normal DNA and DNA alkylated with dimethyl sulphate (DMS), N-methyl-N-nitrosourea (MNUA) and N-ethyl-N-nitrosourea (ENUA) has been investigated using analytical ultracentrifugation techniques. For control T7-DNA (w.st. denatured form 12.5 - 10(6) daltons) the rate of degradation at 37 degr...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(76)90004-1
更新日期：1976-05-01 00:00:00
abstract：:A detailed subfractionation of the non-pregnant porcine corpus luteum (CL) was performed employing differential centrifugation. Marker enzyme assays (i.e., lactate dehydrogenase for the cytosol, NADPH-cytochrome P450 reductase for the endoplasmatic reticulum, catalase (CAT) for peroxisomes, glutamate dehydrogenase for...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2003.10.002
更新日期：2004-01-15 00:00:00
abstract：:Glucocorticoids therapy is strongly limited since extended glucocorticoids can cause serious side effects, including increased susceptibility to develop the bone disease osteoporosis. Despite its side effects recognized importance to clinicians, seldom is known about how glucocorticoids directly impact bone-forming os...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2013.11.004
更新日期：2014-01-25 00:00:00
abstract：:AKR1B10 is a human-type aldo-keto reductase. The up-regulation of AKR1B10 has been associated with various cancers including non-small cell lung carcinoma, viral and bacterial infections, and skin diseases. However, the mechanisms underlying AKR1B10 gene regulation are not fully understood. We previously indicated the...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.02.008
更新日期：2017-10-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.08.020
更新日期：2016-10-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.09.009
更新日期：2014-11-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(79)90041-3
更新日期：1979-05-01 00:00:00
abstract：:Until the last decade, two unrelated aldehyde dehydrogenase (ALDH) superfamilies, i.e. the phosphorylating and non-phosphorylating superfamilies, were known to catalyze the oxidation of aldehydes to activated or non-activated acids. However, a third one was discovered by the crystal structure of a bifunctional enzyme ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.11.006
更新日期：2013-02-25 00:00:00
abstract：:Pyrrolizidine alkaloids (PAs) comprise a large group of more than 660 secondary metabolites found in more than 6000 plant species worldwide. Acute PA intoxication induces severe liver damage. Chronic exposure to sub-lethal doses may cause cumulative damage or cancer. Nuclear receptor activation often constitutes a mol...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2018.04.017
更新日期：2018-05-25 00:00:00
abstract：:The alkylation of hemoglobin is a proposed dose monitor for chemical carcinogens and mutagens. The binding of fifteen chemical carcinogens and mutagens to rat hemoglobin was determined. Direct acting carcinogens and indirect acting carcinogens including aromatic amines, halogenated hydrocarbons, nitrosamines, polycycl...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(81)90048-x
更新日期：1981-01-01 00:00:00
abstract：:The clinical use of doxorubicin is associated with dose limiting cardiotoxicity. This is a manifestation of free radical production triggered by doxorubicin. Therefore, we evaluated the efficacy of febuxostat, a xanthine oxidase inhibitor and antioxidant, in blocking cardiotoxicity associated with doxorubicin in rats....
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.05.013
更新日期：2015-07-25 00:00:00
abstract：:Women all over the world are exposed to an unavoidable contamination by organochlorine pesticides and other chemical pollutants. Many of them are considered as xenoestrogens and have been associated with the development and progression of breast cancer. We have demonstrated that the most prevalent pesticide mixtures f...
journal_title：Chemico-biological interactions
pub_type： 信件
doi：10.1016/j.cbi.2017.03.001
更新日期：2017-04-25 00:00:00
abstract：:Resveratrol, a polyphenol, found in skin of red grapes, peanuts and berries possesses anti-inflammatory, anti-carcinogenic and lipid modulation properties. Here, we demonstrate in vivo antifibrotic activity of resveratrol in a mammalian model, wherein hepatic fibrosis was induced by N'-nitrosodimethylamine (NDMA) admi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.07.007
更新日期：2014-09-25 00:00:00
abstract：:The antitumor activity of a series of diorganotin dihalide and di-pseudohalide complexes, R2SnX2, L2, where R = Methyl (Me), Ethyl (Et), n-Propyl (Pr), n-Butyl (Bu) or Phenyl (Ph); X = F, Cl, Br, I or NCS; and L = O- or N- donor organic ligand, which were modelled on the active platinum complexes, has been investigate...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(80)90075-7
更新日期：1980-10-01 00:00:00
abstract：:The metabolic activation of [14C]phenol resulting in covalent binding to proteins has been studied in rat liver microsomes. The covalent binding was dependent on microsomal enzymes and NADPH and showed saturation kinetics for phenol with a Km-value of 0.04 mM. The metabolites hydroquinone and catechol were formed at r...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(85)80140-x
更新日期：1985-11-01 00:00:00
abstract：:Sophoricoside (SOPH) is an isoflavone glycoside isolated from the fruits of Sophora japonica. Since its first isolation in 1961, there are rare findings about the effects of SOPH on reproductive system. In the present study, the pregnant mice administrated by different doses of SOPH were used to explore the effect of ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.05.009
更新日期：2014-08-05 00:00:00
