Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Maleates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1988

Inhibition of lipid peroxidation by disulfiram and diethyldithiocarbamate does not prevent hepatotoxin-induced cell death in isolated rat hepatocytes. A study with allyl alcohol, tert-butyl hydroperoxide, diethyl maleate, bromoisovalerylurea and carbon tetrachloride.

The relationship between lipid peroxidation and cell death, induced by a number of hepatotoxins, was studied in isolated rat hepatocytes. Disulfiram (DSF) and diethyldithiocarbamate (DDC) completely prevented lipid peroxidation, induced by allyl alcohol, tert-butyl hydroperoxide (t-BHP), diethyl maleate (DEM), bromoisovalerylurea (BIU) and carbon tetrachloride (CCl4). Lipid peroxidation was measured by the formation of both thiobarbituric acid positive material and conjugated dienes. However, DSF and DDC did not protect against cell death, induced by these hepatotoxins. In the presence of DSF or DDC, cell death occurred even earlier in time. We conclude that cell death can occur in the absence of lipid peroxidation. Therefore, lipid peroxidation is not a requisite for the induction of cell death.

1-Propanol↗
PubMed1989

The inhibition of lipid peroxidation by disulfiram prevents the killing of cultured hepatocytes by allyl alcohol, tert-butyl hydroperoxide, hydrogen peroxide and diethyl maleate.

Disulfiram is a potent antioxidant that prevented the peroxidation of microsomal phospholipids induced by ADP/Fe3+ at concentrations as low as 1 microM. However, disulfiram had a biphasic action when used to assess the role of lipid peroxidation in the killing of cultured hepatocytes by an acute oxidative stress. At a relatively low concentration (10 microM), the antioxidant activity of disulfiram predominated, and there was protection against the killing of the hepatocytes by allyl alcohol, tert-butyl hydroperoxide, hydrogen peroxide, and diethyl maleate. As the concentration of disulfiram was increased above 10 microM, the extent of protection progressively decreased. Thus, with higher concentrations of disulfiram, there was a second action whose consequence is to obscure the protective effect of the lower doses. With the agents studied, this additional and as yet undefined action of disulfiram leads to the killing of the hepatocytes by a mechanism that is unrelated to the peroxidation of lipids. This biphasic action of disulfiram must be appreciated in any attempt to use this compound to assess the role of lipid peroxidation in toxic cell injury.

1-Propanol↗
PubMed1988

Effect of diethyl maleate on hepatic ornithine decarboxylase.

Diethyl maleate (DEM), a well-known glutathione (GSH) depletor, causes a dose-dependent increase in hepatic ornithine decarboxylase (ODC) activity as well as heme oxygenase activity in rats. Considering the important role ODC has in polyamine biosynthesis in response to endogenous and exogenous stimuli, further extensive studies on the effect of DEM on ODC in relation to its GSH-depleting effect were carried out. Specifically, concomitant with the profound decrease in GSH content, the higher dose of DEM (1284 mg/kg) caused a marked increase in ODC activity (about 1000 times that of the control) at 12 hr after its administration. DEM at this dose also caused a marked increase in heme oxygenase activity, but the effects on cytochrome P-450 content and aminopyrine demethylase activity were less extensive. The increases in ODC and heme oxygenase activities evoked by DEM were almost completely blocked by pretreatment of rats with either actinomycin D or cycloheximide. Parallel to the increase in ODC activity, DEM caused a profound increase in putrescine content in the liver, while the agent reduced spermine content. The administrations of alpha-difluoromethylornithine and 1,3-diaminopropane resulted in the inhibition of DEM-mediated induction of ODC, but not heme oxygenase. In contrast, methylglyoxal bis(guanylhydrazone) inhibited the induction of both ODC and heme oxygenase evoked by DEM. The DEM-induced ODC exhibited two phases of decay with the prolonged half-lives of 26 and 223 min. Additionally, the elution profile from DEAE-Sepharose CL-6B column chromatography of cytoplasmic fraction from DEM-treated rat liver exhibited two peaks of ODC activity. These findings add new insight into the biochemical effect of DEM on hepatic polyamine metabolism in addition to its GSH-depleting effect.

Aminopyrine N-Demethylase↗
PubMed1992

Induction of metallothionein by diethyl maleate.

Metallothionein (MT) is a sulfhydryl-rich protein whose levels are increased by administration of a variety of agents including metals, cytokines, and oxidative stress agents. Recent studies have suggested that MT is involved in protecting against various forms of oxidative stress, but little is known about the induction of MT by oxidative stress agents. Diethyl maleate (DEM) causes oxidative stress by depleting glutathione levels and is quite effective at increasing hepatic concentrations of MT. The purpose of the current study was to learn more about the relationship between induction of MT and oxidative stress by characterizing this increase in hepatic MT levels produced by DEM. Administration of DEM (3 to 9 mmol/kg, sc) increased hepatic MT concentration in mice as much as 37-fold to 213 micrograms MT/g liver, which is similar to the hepatic MT level seen after administration of other effective MT inducers, such as Cd. The maximal increase of hepatic MT took place 12 to 24 hr after administration of 5 mmol DEM/kg. This rise in MT was preceded by a 60% depletion of hepatic glutathione 3 hr after DEM and increases in both MT-I and MT-II mRNA, which reached a peak 6 to 9 hr after DEM. Administration of DEM (3-5 mmol/kg, sc) also increased MT levels in Sprague-Dawley rats. Pretreatment with DEM protected against Cd-induced hepatotoxicity in a fashion which suggested that a functional MT was being synthesized. In summary, DEM is a highly effective inducer of MT which increases MT at the mRNA level.

Animals↗
PubMed1992

Examination of potential mechanism(s) of metallothionein induction by diethyl maleate.

Diethyl maleate (DEM) is a glutathione-depleting agent that can increase the levels of the sulfhydryl-rich protein metallothionein (MT) in liver. The purpose of the present study was to examine the mechanism(s) by which DEM increases mouse hepatic MT levels. DEM appears to be an indirect MT inducer as suggested by the lack of increase in MT levels when cultured mouse hepatocytes were exposed to DEM. Four possible mechanisms by which indirect MT inducers may cause an elevation in MT concentrations in liver were examined. Zn levels did not increase prior to the increase in hepatic MT, thus, a Zn redistribution to the liver is not the cause of the liver MT induction by DEM. The adrenal gland products were not required for MT induction in liver, as adrenalectomy did not abolish the increase in hepatic MT caused by DEM. The elevation in liver MT does not appear to be due solely to the decrease in liver glutathione (60%) in the initial hour after DEM, because phorone, which decreases liver glutathione (80%), produced only a fourfold increase in hepatic MT. Activation of macrophages does not seem to account for the rise in liver MT levels, as there was no increase in abundance of cytokine mRNAs for TNF-alpha, IL-1 beta, or IL-6 in the liver. These data suggest that the induction of hepatic MT by DEM does not occur in response to (1) an increase in liver Zn that precedes the increase in liver MT, (2) release of adrenal gland products, (3) decrease in liver glutathione, or (4) increased cytokine gene expression.

Adrenalectomy↗
PubMed1992

Lung mitochondrial function following oxygen exposure and diethyl maleate-induced depletion of glutathione.

Diethyl maleate (DEM) pretreatment has previously been shown to result in a transient depletion of lung glutathione and an associated decrease of the time to the onset of rat mortality resulting from exposures to 100% oxygen in vivo. The effects of oxygen exposure on mitochondrial energy metabolism were assessed by measurements of ADP-stimulated rates of O2 utilization by lung homogenates prepared from untreated and DEM-treated rats following 4 and 24 hr of exposure to either air or 100% oxygen. Twenty-four hours of oxygen exposure of untreated rats resulted in significant decreases in lung homogenate ADP-stimulated rates of respiration supported by the substrates, pyruvate, isocitrate, and alpha-ketoglutarate. No changes were observed in succinate-supported respiration, indicating that oxygen exposure appears to adversely affect NAD-linked rather than FAD-linked pathways of mitochondrial energy metabolism. The decreased lung mitochondrial glutathione, observed 4 hr following DEM treatment, returned to normal levels following 24 hr of air and oxygen exposure. No effects of glutathione depletion were observed on ADP-stimulated rates of respiratory activity 4 hr following DEM treatment. The DEM-induced transient depletion of glutathione also did not result in any additional detrimental effects on mitochondrial respiratory activity following 24 hr of oxygen exposure in vivo. These results suggested that transient mitochondrial depletion of glutathione does not accelerate the oxygen-induced impairment of mitochondrial energy metabolism. The onset of mortality associated with DEM-pretreatment might therefore result from a failure of glutathione-dependent cytosolic protective mechanisms, rather than from an increased rate of oxygen-induced mitochondrial damage.

Adenosine Diphosphate↗
PubMed1994

Blockade of N-methyl-D-aspartate receptors by MK-801 (dizocilpine maleate) rescues motoneurones in developing rats.

In rats following nerve injury at birth a large proportion of motoneurones to the soleus muscle dies. Blocking of N-methyl-D-aspartate (NMDA) receptors by MK-801 (dizocilpine maleate) for 12 days after nerve injury at birth leads to rescue of a proportion of motoneurones destined to die. Retrograde labelling of soleus motoneurones shows that 6-8 weeks after crushing the sciatic nerve in one hindlimb, only 10.9 +/- 2.3% of the motoneurones have survived. In animals treated with an NMDA receptor blocker MK-801 (2 mg/kg i.p., from birth to 12 days old) 50.6 +/- 3.8% of soleus motoneurones survived. This neuroprotective effect of MK-801 was dose dependant, since after treatment with lower doses (0.5 mg/kg; 1 mg/kg) fewer motoneurones survived (13.7% and 34.5%, respectively). To assess the effect of treatment with MK-801 on survival of alpha-motoneurones only, the number of soleus motor units was established physiologically. After nerve injury alone only 4.2 +/- 1.2 of the 29-30 soleus motor units were present, while in animals treated with MK-801 (2 mg/kg) 14 +/- 1.5 motor units were identified. The neuroprotective effect of MK-801 was not confined to soleus motoneurones but was also apparent on motoneurones to the extensor digitorum longus (EDL). In untreated EDL muscles of the 40 motor units only 5.5 +/- 1.7 motor units survived neonatal nerve injury and this number increased to 18 +/- 2.6 after treatment with MK-801. The neuroprotective effect of MK-801 was apparent regardless of whether the nerve lesion was carried out close to or far from the soleus muscle.

Animals↗
PubMed1988

Inhibitory effect of salicylate on 2,4-dinitrophenol and diethyl maleate in isolated rat intestinal epithelial cells.

Studies on the mechanism of chemically induced intestinal epithelial injury were carried out using isolated, rat small intestinal epithelial cells. Compounds such as 2,4-dinitrophenol (DNP) and diethyl maleate (DEM), caused NADH loss, an increase in cytosolic Ca2+ concentration and protein thiol loss. Further, these compounds accelerated cell aggregation and decreased cell viability. Calmodulin antagonists inhibited protein thiol loss induced by either of the compound, inhibited cell aggregation and prolonged cell viability, but did not influence NADH loss. It has been reported that the calmodulin-binding protein may regulate cytoskeletal activity. Therefore, the inhibition of protein thiol loss by calmodulin antagonist may be due to a dissociation of calmodulin-binding proteins from cytoskeletal elements. Salicylate also inhibited protein thiol loss induced by DNP and DEM, and inhibited cell aggregation. However, salicylate may have a direct effect in reducing the cytosolic free Ca2+ concentration by complexation and subsequent facilitated release of Ca2+ from cells. Further, in the present study, the induction of cell aggregation may be caused by the appearance of specific sites on the cell membrane surface to which arsenazo III could adsorb, since adsorption of arsenazo III to the isolated epithelial cells seemed to correlate with increased cell aggregation.

Animals↗
PubMed1993

Anticonvulsant agents, dizocilpine maleate, enadoline and HA 966 have different effects on N-methyl-DL-aspartate-induced immediate early gene induction in mice.

Administration of N-methyl-DL-aspartate (85 mg/ml) was given by infusion (0.14 ml/min) until a clonic seizure was elicited. In situ hybridization was used to assess regional levels of four immediate early gene messenger RNA levels (c-fos, c-jun, junB, and a nerve growth factor induced gene, NGFI-A). Messenger RNA levels were highest at 25 min following infusion of N-methyl-DL-aspartate. c-jun messenger RNA levels remained elevated for over 2 h; however, c-fos, junB and, NGFI-A messenger RNA levels had returned to control levels by this time. Expression was detected in the hippocampus, hypothalamus and piriform cortex. Pre-treatment (30 min prior to N-methyl-DL-aspartate) with the anticonvulsant drugs dizocilpine maleate (1 mg/kg) and HA 966 (200 micrograms, i.c.v.) resulted in significantly reduced immediate early gene messenger RNA levels in the hypothalamus and piriform cortex, and attenuated levels in the hippocampus. Pre-treatment with the anticonvulsant agent enadoline (3 mg/kg), given at an anticonvulsant dose, did not result in reduced immediate early gene messenger RNA levels. These results suggest that monitoring immediate early gene expression may lead to advances in the understanding of the mechanism of action of many pharmacological agents, such as the kappa-opioid agonist enadoline.

Animals↗
PubMed1994

Expression and distribution of hsp71 and hsc73 messenger RNAs in rat brain following heat shock: effect of dizocilpine maleate.

Induction of hsp71 mRNA, coding for the inducible heat shock protein HSP71, and the constitutively expressed, hsc73 mRNA coding for the heat shock cognate protein HSC73 were studied after heat shock using northern blotting and in situ hybridization. Two cDNA oligonucleotides complementary to the messenger RNAs for hsp71 and hsc73 and suitable for in situ hybridization were designed and shown to hybridize selectively to their respective mRNAs. The inducible hsp71 was rapidly synthesized in brain after heat shock and disappeared in 6 h. A high level of expression was observed first in the dentate granule cell layer and then slightly later in the hippocampal pyramidal cell layer. There was also a dramatic increase in the granular layer of the cerebellar cortex. There was a more modest increase in expression of hsc73 after heat shock in forebrain and in cerebellum (granular layer). The N-methyl-D-aspartate receptor antagonist dizocilpine maleate (0.5 mg/kg, i.p.), given 15 min before heat shock, significantly reduced the expression of hsp71 but had no effect on hsc73. These results suggest that glutamate plays a role in heat shock-induced expression of hsp71 in brain.

Animals↗
PubMed1986

The radiosensitizing effects of misonidazole (MISO) in combination with diethyl maleate (DEM) in mouse mammary tumors.

Large radiosensitization of C3H/He mouse mammary tumors was obtained with the combination of a non-protein sulfhydryl (NPSH) depletor, diethyl maleate (DEM), and misonidazole (MISO), compared with MISO alone over a range of MISO dose. The difference in enhancement ratios (ER's) for these two treatments was especially prominent at small MISO doses. ER's of 2.06 and 1.44 were obtained, respectively, by combined treatment with DEM (760 mg/kg) and MISO (100 mg/kg) or treatment with MISO alone. Radiosensitization of tumors by DEM alone was observed for doses over 600 mg/kg. When DEM was combined with MISO (100 mg/kg), ER's of the combination were larger than that of MISO alone, for doses over 400 mg/kg of DEM. Similarly, in case of DEM plus MISO (300 mg/kg), the ER's became larger than MISO alone, for doses over 200 mg/kg of DEM. The NPSH content in untreated tumors was 1.08 mmole/kg on the average and no changes in NPSH content was observed after MISO treatment. DEM treatment markedly reduced the NPSH content of tumors as a function of DEM dose and this decrease in NPSH was not significantly affected by MISO treatment. Tumor NPSH was reduced to 24% or less of control by administration of 760 mg/kg of DEM with or without MISO. These results are consistent with competition theory of NPSH and electron affinic radiosensitizers.

Animals↗
PubMed1980

Effect of diethyl maleate on acrylamide induced neuropathy in rats.

Pre-administration of diethyl maleate (DEM) to rats resulted in an earlier onset and development of hind limb paralysis following acrylamide administration than in rats treated with acrylamide only. A marked depletion of brain biogenic amine content and of glutathione levels was also observed in the DEM pretreated groups. Depletion of cellular glutathione would appear to lead to an increased neurotoxicity of acrylamide.

Acrylamides↗
PubMed1982

Carbon tetrachloride-mediated expiration of pentane and chloroform by the intact rat: the effects of pretreatment with diethyl maleate, SKF-525A and phenobarbital.

Measurements were made of pentane, a produce of lipid peroxidation, and chloroform (CHCl3), a product of the reproductive metabolism of carbon tetrachloride (CCl4), expired by rats administered CCl4 plus either phenobarbital (PB), 2-diethylaminoethyl-2,2-diphenyl valerate hydrochloride (SKF-525A), or diethyl maleate (DEM). In rats fed a standard laboratory diet, treatment with PB prior to injection of CCl4 increased expiration of both CHCl3 and pentane. SKF-525A pretreatment decreased the metabolism of CCl4 and CCl4-induced lipid peroxidation. DEM, a depleter of intracellular glutathione, increased lipid peroxidation. In rats fed 10% corn oil diets that contained either 0 or 40 IU of dl-alpha-tocopherol acetate, oxidant stresses caused by glutathione depletion and CCl4-intoxication were found to be additive.

Animals↗
PubMed1984

Modification of butylated hydroxytoluene-induced pulmonary toxicity in mice by diethyl maleate, buthionine sulfoximine, and cysteine.

Treatment of mice with diethyl maleate (DEM) or buthionine sulfoximine (BSO) significantly enhanced the lung injury caused by butylated hydroxytoluene (BHT). Conversely, cysteine protected mice from the lung toxicity of BHT. BHT administration to mice produced a time-dependent reduction of glutathione (GSH) content in the lung, but not in the liver. These results support the concept that conjugation of 2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone (BHT-quinone methide), a proposed reactive metabolite of BHT, with GSH is involved in the detoxification of BHT in mice.

Animals↗
PubMed1991

The effect of glutathione monoethyl ester on the potentiation of the acute toxicity of methyl parathion, methyl paraoxon or fenitrothion by diethyl maleate in the mouse.

Depletion of hepatic glutathione in the mouse by pretreatment with diethyl maleate (DEM) is known to potentiate the acute toxicities of many dimethyl-substituted organothiophosphate insecticides. However, certain studies have raised doubts regarding the participation of glutathione in the detoxification of methyl parathion in the mouse, and hence the putative mechanism of action of DEM-induced potentiation of this insecticide. The present study evaluates the hypothesis that DEM potentiates the acute toxicities of methyl parathion, methyl paraoxon, and fenitrothion by a mechanism other than glutathione depletion. One hour following pretreatment of mice with DEM (0.75 ml/kg i.p.), glutathione was markedly depleted and the acute toxicities of methyl parathion, methyl paraoxon and fenitrothion were potentiated. Administration of glutathione monoethyl ester (20 mmol/kg p.o.) to DEM-pretreated mice attenuated DEM-depletion of hepatic glutathione, or maintained glutathione at or above control levels. However, glutathione monoethyl ester did not alter the DEM-induced potentiation of the lethality of these insecticides. Furthermore, administration of glutathione monoethyl ester to naive mice increased hepatic glutathione levels, but did not affect the percentage of animals succumbing to a challenge dose of methyl parathion, methyl paraoxon, or fenitrothion. These data indicate that DEM potentiates the toxicity of methyl parathion, methyl paraoxon or fenitrothion by a mechanism unrelated to hepatic glutathione content.

Animals↗
PubMed1991

Protein damage and lipid peroxidation: effects of diethyl maleate, bromotrichloromethane and vitamin E on ammonia, urea and enzymes involved in ammonia metabolism.

Changes in ammonia and urea were investigated as potential marker products of free radical damage to protein and subsequent metabolism of those damaged proteins in vivo. Both serum and liver lipid peroxidation products as measured by thiobarbituric-acid-reactive substances (TBARS) were increased by feeding rats a vitamin-E-deficient diet. The acute injection of diethyl maleate and bromotrichloromethane (DEM/BrCCl3) increased TBARS in liver of rats fed a vitamin-E-deficient diet. The concentrations of ammonia and urea in the serum and liver did not correlate with lipid peroxidation. The activities of liver glutaminase and arginase were decreased by DEM/BrCCl3 treatment in rats fed vitamin-E-deficient diet. Glutamate-ammonia ligase activity was decreased by vitamin-E-deficient diet but not by DEM/BrCCl3 treatment. Ornithine carbamoyltransferase, arginosuccinate synthase, argininosuccinate lyase and glutamate dehydrogenase (NAD(P)+) were not affected by dietary vitamin E or by DEM/BrCCl3. The data suggest that the concentrations of ammonia and urea, major by-products of nitrogen metabolism, are unchanged by the oxidant damage and lipid peroxidation, and that their control in vivo is a dynamic equilibrium of various metabolic pathways.

Ammonia↗
PubMed1992

Effect of diethyl maleate on glutathione, hepatic and renal cortical perfusion, and portal 6-ketoPGF1 alpha and TxB2 levels in swine.

1. Effects of diethyl maleate (DEM) mediated glutathione (GSH) depletion on hepatic and renal cortical blood flow (perfusion), plasma GSH, and portal prostacyclin (6-ketoPGF1 alpha) and thromboxane (TxB2) were determined in anaesthetized swine. 2. Although DEM depleted hepatic GSH to 25% of control, plasma GSH increased 10-fold in comparison to controls. DEM caused a drop in blood pressure and renal cortical perfusion but had no effect on hepatic perfusion or portal 6-ketoPGF1 alpha or TxB2 levels. 3. Possibly, the unexpected rise in plasma GSH may have inhibited prostanoid synthesis, preventing any alterations in tissue perfusion that may have occurred following tissue GSH depletion.

6-Ketoprostaglandin F1 alpha↗
PubMed2006

Poly(2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate, dibutyl maleate) membrane controlled clonidine zero-order release.

Poly(2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate, dibutyl maleate) membrane was synthesized by UV curing method in our laboratory for the first time. When above-mentioned monomers were in the weight ratio of 4:4:2, the membrane not only had perfect permeation property but also had excellent plasticity, so the membrane made from monomers in the ratio of 4:4:2 was chosen as an optimized membrane. The optimized membrane provided perfect linear permeation properties in clonidine transdermal drug delivery system. The permeation rate decreased in proportion to the thickness of membrane. When the concentrations of clonidine were in the range of 0.5-7.0mg/ml, the permeation rate was proportional to the square root of clonidine concentrations. The optimized membrane was characterized by FTIR, DSC and SEM.

Acrylates↗