Abstract：
:Although N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methylmethanesulfonate (MMS) cause injury and malondialdehyde formation in rat hepatocytes, MNNG toxicity is much more sensitive to inhibition by antioxidants. In order to quantify the relationship between toxicity and antioxidation potential, we compared 14 antioxidants that protected against MNNG and MMS toxicity. Chemoprotection was quantified as the concentration that delayed by 1 h the decline in trypan blue exclusion to less than or equal to 50%. While chemoprotection against MNNG and antioxidant efficacy were directly related (R = 0.86), chemoprotection against MMS and antioxidant efficacy were unrelated (R = 0.37). Since we hypothesized that protection against MMS involved stabilization of membranes, the capacity of the 14 compounds to stabilize membranes in an unrelated system (i.e. prevention of erythrocyte osmotic rupture) was assayed. Chemoprotection against both MNNG and MMS correlated with reduced RBC fragility (R = 0.97 and 0.70, respectively). One of the better protecting compounds, 4b,5,9b,10-tetrahydroindeno[1,2-b]indole, was also protective against hepatocellular toxicity mediated by acetaminophen, carbon tetrachloride and tert-butyl hydroperoxide, suggesting a fundamental basis in the mechanism of chemoprotection. We propose that methylating agents and perhaps other chemical toxicants destabilize cellular membranes resulting in hepatocellular injury. For MNNG, radical mediated events may result in membrane destabilization; for MMS, membranes are destabilized without concurrent radical events. The current studies provide a basis for future work to determine structure-activity relationships of chemoprotective agents, examine protection mechanisms, and develop better protective compounds.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Shertzer HG,Sainsbury M,Graupner PR,Berger MLdoi
10.1016/0009-2797(91)90009-vsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
123-41issue
2eissn
0009-2797issn
1872-7786pii
0009-2797(91)90009-Vjournal_volume
78pub_type
杂志文章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：:Comamonas testosteroni (C. testosteroni) ATCC11996 is a gram negative bacterium which can use steroid as a carbon and energy source. 3,17β-hydroxysteroid dehydrogenase (3,17β-HSD) is a key enzyme for the degradation of steroid hormones in C. testosteroni. The LuxR regulation family is a group of regulatory proteins wh...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.03.002
更新日期：2017-10-01 00:00:00
abstract：:Treatment of rats with two different doses of CCl4 (respectively 2.5 and 0.5 ml/kg body wt. intragastrically) is followed by a rapid increase in the cAMP content of the liver. With 0.5 ml of CCl4, the increase occurs as early as 30 min after poisoning, namely about 4-5 h before the onset of triglyceride accumulation i...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(79)90089-9
更新日期：1979-06-01 00:00:00
abstract：:The present study sought to evaluate the hypoglycemic activities of free glycosylated flavonoids and flavonoid complexes with vanadium(IV), (VO(IV)), on glycemia in experimental diabetic rats. Besides free kaempferol-3,7-O-(alpha)-dirhamnoside and kaempferol-3-neohesperidoside, complexes of these flavonoids with VO(IV...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2006.07.010
更新日期：2006-11-07 00:00:00
abstract：:We have studied the effect of muscular dystrophy by merosin deficiency on mouse thymus acetyl- (AChE) and butyrylcholinesterase (BuChE). The organ contains AChE and BuChE activities. Merosin deficiency causes an important decrease (46%) in AChE specific activity. Thymus produces dimers, monomers and tetramers of AChE,...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.10.092
更新日期：2005-12-15 00:00:00
abstract：:It has been suggested that the binding of iron(III) by phosvitin involves the phosphoric radicals of phosphorylserine residues, many of which are arranged in rows of several consecutive phosphoamino acids. In this paper we present evident that, unlike free phosphorylserine which does not interact with Fe(III), polypho...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(76)90161-7
更新日期：1976-10-02 00:00:00
abstract：:11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) physiologically catalyzes the interconversion of receptor-active 11-hydroxy glucocorticoids (cortisol) to their receptor-inactive 11-oxo metabolites (cortisone), thereby acting as important pre-receptor control device in regulating access of glucocorticoid horm...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(02)00180-1
更新日期：2003-02-01 00:00:00
abstract：:Butyrylcholinesterase (BChE) constitutes the first line defense in the serum of higher organisms and is a marker for toxic exposure. Indole-3-acetic acid (IAA) is a major plant growth hormone of the auxin class, affecting cell enlargement, and differentiation. As a result of the industrial usage, this agrochemical is ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.10.061
更新日期：2005-12-15 00:00:00
abstract：:Catalytic scavengers of organophosphates (OPs) are considered very promising antidote candidates for preventing the adverse effects of OP intoxication as stand alone treatments. This study aimed at correlating the in-vivo catalytic efficiency ((kcat/KM)[Enzyme]pl), established prior to the OP challenge, with the sever...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.04.039
更新日期：2016-11-25 00:00:00
abstract：:Intracellular calcium (Ca(2+)i) overload induced by chronic hypoxia alters Ca(2+)i homeostasis, which plays an important role on mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve Ca(2+)i handling in hypoxic myocardial injury. Cardiomyocytes isolated from neonat...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.04.022
更新日期：2015-07-05 00:00:00
abstract：:Rabbit bone marrow mitochondria, stripped of their outer membrane (mitoplasts), have been shown to carry out the NADPH-dependent bioactivation of radiolabelled benzene in vitro to metabolites capable of covalently binding to mtDNA, thereby inhibiting transcription. The metabolites of benzene produced in bone marrow ce...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(84)90057-7
更新日期：1984-04-01 00:00:00
abstract：INTRODUCTION:An imbalance between oxidants and antioxidants in favour of oxidants, potentially leading to damage, is termed oxidative stress. Antioxidants (AO), either enzymatic or non-enzymatic, are the ones that can reduce diverse effects of pro-oxidants such as DNA, proteins and lipids damage. Chalcones (1,3-diaryl-...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2020.109084
更新日期：2020-06-01 00:00:00
abstract：:p-Aminobenzoic acid (p-ABA) derivatives were evaluated as acetylcholinesterase inhibitors (AChEIs). Finding a correlation between AChE activity with the partition coefficient (log P) and the highest occupied molecular orbital (HOMO) energy of the compounds. ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.10.055
更新日期：2005-12-15 00:00:00
abstract：:The atypical butyrylcholinesterase (aBuChE) from Oryzias latipes shares approximately 65% sequence similarity to both acetylcholinesterase and butyrylcholinesterase and was studied for its capacity to spontaneously reactivate following inhibition by organophosphorus nerve agents. Like other cholinesterases, aBuChE was...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.03.016
更新日期：2016-11-25 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：:A microspectrophotometric method for assaying cytochrome P-450 in fresh 24 micrometer unfixed cryostat sections of rat liver has been developed. When used to assay this cytochrome in sections of microsomal preparations it has yielded results equivalent to those obtained by the conventional spectrophotometric assay of ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(78)90108-4
更新日期：1978-03-01 00:00:00
abstract：:This study investigated the effect of inducers on the major enzymes responsible for metabolising the quinone antitumor agent mitoxantrone, and on its cytotoxicity in MCF 7 human breast cancer cells. Four inducers were used: 1,2-benzanthracene (BA), phenobarbitone (PB); rifampicin (R) and dexamethasone (DEX). Of these,...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(94)03603-6
更新日期：1995-07-14 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：:Organophosphate (OP) based pesticides are highly toxic compounds that are still widely used in agriculture around the world. According to World Health Organization (WHO) data, it is estimated that between 250,000 and 370,000 deaths occur yearly around the globe as a result of acute intoxications by pesticides. Current...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.05.034
更新日期：2016-11-25 00:00:00
abstract：:A new, direct method for determining superoxide dismutase activity is presented in this study. This method is based on measurement of one of the products of the superoxide dismutase reaction, hydrogen peroxide. Hydrogen peroxide is quantitated using a coupled reaction where horseradish peroxidase catalyzes the formati...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(93)90112-c
更新日期：1993-01-01 00:00:00
abstract：:Acetaldehyde (AA) and methylglyoxal (MG) are reactive, ubiquitous aldehydes, present in the environment and endogenously formed in animals and humans. They have both been shown to readily form DNA adducts under simulated physiological conditions. We report here on the use of cultured normal and SV40T antigen-immortali...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(97)00107-5
更新日期：1998-01-30 00:00:00
abstract：:Medium-chain dehydrogenases/reductases (MDR) alcohol dehydrogenases exhibit multiple forms through a number of gene duplications. A crucial duplication was the one leading from the glutathione-dependent formaldehyde dehydrogenase line to the liver alcohol dehydrogenase (ADH) lines of vertebrates, the first duplication...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(00)00294-5
更新日期：2001-01-30 00:00:00
abstract：:Variable temperature 1H-nuclear magnetic resonance (NMR) has been used to study the interaction of the RNA trimer, GpCpA, with the intercalators ethidium bromide and the acridine derivatives; proflavin, 9-amino-acridine, acridine orange, acridine yellow and acriflavin. The complexes formed were studied at nucleic acid...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(84)90135-2
更新日期：1984-06-01 00:00:00
abstract：:MnFe2O4 nanoparticles (NPs) are commonly produced in some occupational settings and may reach high concentration in activities such as arc-welding or ferroalloy metallurgy. Manganese is an essential cofactor in enzyme activities but it has been demonstrated that long-term exposure to excessive levels can lead to "mang...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2018.07.020
更新日期：2018-09-25 00:00:00
abstract：:V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is a member of CRK family and act as an adaptor protein participating in intra-cellular signal transduction. The role of CRKL in gastric cancer (GC) remains unclear. In this study, we show that CRKL was aberrantly highly expressed in both GC tumor specimens a...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2013.09.003
更新日期：2013-11-25 00:00:00
abstract：:Two aldehyde dehydrogenases (ALDH) were purified from the liver of black seabream (Acanthopagrus schlegeli). Chromatography of the liver homogenate on an alpha-cyanocinnamate-Sepharose affinity column results in two activity peaks using acetaldehyde as the substrate. The eluate was subjected to another affinity chroma...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(02)00200-4
更新日期：2003-02-01 00:00:00
abstract：:Methylglyoxal (2-oxopropanal) is a cytotoxic compound that can be formed endogenously as a by-product of glycolytic pathway; so its concentration is expected to increase when glycolysis activity increases such as during embryo development. In this work we study the effect of exogenous methylglyoxal on development and ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(98)00048-9
更新日期：1998-07-24 00:00:00
abstract：:Polyphenols, coumarin (1,2-benzopyrone) and chromone (1,4-benzopyrone), are naturally occurring constituent of variety of plant species. They have attracted immense interest because of their diverse pharmacological activities. Not much was known about biological activities of acetyl derivative (polyphenolic acetates) ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.02.025
更新日期：2010-05-14 00:00:00
abstract：:High content of hydroxyflavones in fruits, vegetables, cereals and herbs makes them a common component of the human diet. Because of their antioxidant, antiviral, antibacterial, anti-inflammatory, anticancer properties they still pay an attention of many scientific centers. Hydroxyflavones may form complexes with meta...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/j.cbi.2017.06.016
更新日期：2017-08-01 00:00:00
abstract：:It was aimed to identify the cytochrome(s) P450 (CYPs) involved in the N-demethylation and N-oxidation of clozapine (CLZ) by various approaches using human liver microsomes or microsomes from human B-lymphoblastoid cell lines. The maximum rates of formation were measured in the microsomal fraction of human livers and ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(99)00006-x
更新日期：1999-04-01 00:00:00
