diethyl-maleate and Body-Weight

The effects of 8-week diethylmaleate (DEM) and clofibric acid (CFA) supplemented diet on blood pressure, body and liver weights, liver antioxidant status and nitric oxide synthase (NOS) activity were investigated in 8-week DOCA-salt treated and untreated Sprague-Dawley male rats. It appeared that DEM and particularly CFA treatments were associated with a significant decrease in blood pressure in DOCA-salt treated rats, and an accentuation of the decreases in body weights in both diet supplemented groups. This was not associated with increases in NO production in the liver. In contrast, hepatic lipid peroxidation was significantly decreased in both DOCA-salt treated and untreated groups on DEM and particularly on CFA supplemented diet. The protective effects of CFA and DEM against hepatic cellular damage could be involved in the decreases in blood pressure in DOCA-salt treated rats, where CFA was more efficient than DEM. In CFA supplemented groups, there was a strong increase in hepatic superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px), and catalase (CAT) activities and in DEM supplemented groups, increases in SOD and CAT activities and in GSH levels were observed. Our data suggest that normalization of blood pressure in DOCA-salt treated rats by CFA was due to an enhancement of the half-life of NO while DEM increased its availability.

Topics: Animals; Blood Pressure; Body Weight; Catalase; Clofibric Acid; Desoxycorticosterone; Diet; Glutathione; Hypolipidemic Agents; Lipid Peroxidation; Liver; Male; Maleates; Nitric Oxide Synthase; Organ Size; Rats; Rats, Sprague-Dawley; Sodium Chloride; Superoxide Dismutase

The modifying effect of diethyl maleate (DEM) on gastric tumor development was studied in rats initially given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and hypertonic sodium chloride (H-NaCl 10% or 5%). Groups of animals were maintained with or without a 0.2% DEM dietary supplement after treatment with MNNG and H-NaCl and sacrificed at week 20. Forestomachs and livers cytosolic NAD(P)H:quinone-acceptor oxidoreductase (QR) activity was also analyzed. The incidences of forestomach severe hyperplasias in the MNNG + H-NaCl --> DEM groups were also significantly higher than in the MNNG + H-NaCl alone group (P < 0.01 and P < 0.05 for 5% and 10% groups, respectively). Similarly, in the glandular stomach, the numbers of preneoplastic pepsinogen 1 altered pyloric glands (PAPGs) in the MNNG + H-NaCl --> DEM groups were significantly increased (P < 0.01 for both concentrations). The QR activities in the groups treated with DEM showed 2- to 3-fold increases as compared with the control level. The results indicate that treatment with 0.2% DEM after MNNG initiation exerts enhancing effects on both forestomach and glandular stomach carcinogenesis. Induction of QR, a Phase II enzyme, activity in the rat stomach by DEM may be associated with promotion of stomach carcinogenesis rather than inhibition.

Topics: Animals; Body Weight; Carcinogenicity Tests; Carcinogens; Carcinoma, Squamous Cell; Gastric Mucosa; Male; Maleates; Methylnitronitrosoguanidine; NAD(P)H Dehydrogenase (Quinone); Papilloma; Pepsinogen A; Rats; Rats, Wistar; Saline Solution, Hypertonic; Stomach; Stomach Neoplasms

An experiment was performed to determine the effect of diethyl maleate (DEM), an in vivo depletor of glutathione, on the response of male and female rats to arsenic deprivation. A 2 x 2 x 2 factorially arranged experiment used groups of six weanling Sprague-Dawley rats. Dietary variables were arsenic at 0 or 0.5 microgram/g and DEM at 0 or 0.25%; the third variable was gender. Animals were fed for 10 wk a casein-ground corn based diet that contained amounts of calcium, phosphorus, and magnesium similar to the AIN-76 diet. DEM supplementation increased blood arsenic in both male and female rats; female rats had the greatest amount of arsenic in whole blood. Although female rats in general had a lower concentration of glutathione in liver, those fed no supplemental DEM, regardless of their arsenic status, had the lowest amounts. Compared to males, female rats had a lower activity of liver glutathione S-transferase (GST). Arsenic deprivation decreased, and DEM supplementation increased liver GST activity in both male and female rats. Lung GST activity was also increased by DEM supplementation in male, but not female, rats. The most striking finding of the study was that compared to males, females had extremely elevated kidney calcium concentrations, and that the elevation was exacerbated by arsenic deprivation. DEM supplementation also exacerbated the accumulation of calcium in the kidney of the female rats. The response of the rat to both DEM and arsenic was, for many variables, dependent on gender. This gender dependence may be explained by the differences in methionine metabolism between male and female rats. Thus, arsenic deprivation apparently can manifest itself differently depending on gender.

Topics: Analysis of Variance; Animals; Arsenic; Body Weight; Calcium; Diet; Female; Glutathione; Glutathione Transferase; Hematocrit; Hemoglobins; Kidney; Liver; Lung; Male; Maleates; Methionine; Organ Size; Rats; Rats, Sprague-Dawley; Sex Characteristics

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.

Topics: Animals; Body Weight; Drug Synergism; Fenitrothion; Glutathione; Liver; Male; Maleates; Methyl Parathion; Mice; Organ Size; Paraoxon

Male F344 rats were administered phenobarbital, polychlorinated biphenyl (PCB), retinol acetate, indomethacin, 6-amino-caproic acid, dexamethasone (DEX) or diethylmaleate (DEM) for one week and then were treated with these chemicals plus butylated hydroxyanisole (BHA) for a further four weeks. Histopathologically, the incidence of BHA-induced forestomach hyperplasia was significantly lower in rats treated with PCB, DEX or DEM than in those treated with BHA alone. However, the inhibition by PCB and DEX was only partial and might have been due to decreased food intake. On the other hand, DEM completely inhibited the hyperplastic response to BHA at a dose of 0.25%, and even at lower doses it demonstrated significant inhibition without any decrease in body weight or food intake. The result that DEM, a tissue glutathione depleting agent, can inhibit BHA-associated forestomach hyperplasia strongly suggests that tissue glutathione may be intimately involved in the induction of forestomach hyperplasia by the antioxidant in rats.

Topics: Aminocaproic Acid; Animals; Body Weight; Butylated Hydroxyanisole; Dexamethasone; Diet; Diterpenes; Drug Interactions; Eating; Indomethacin; Liver; Male; Maleates; Organ Size; Phenobarbital; Polychlorinated Biphenyls; Rats; Rats, Inbred F344; Retinyl Esters; Stomach; Vitamin A

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.

Topics: Animals; Body Weight; Buthionine Sulfoximine; Butylated Hydroxytoluene; Cysteine; Drug Synergism; Glutathione; Liver; Lung; Male; Maleates; Methionine Sulfoximine; Mice; Organ Size

Male New Zealand White rabbits were orally given 0.05 mg of aflatoxin B1 (AFB1)/kg of body weight daily for 10 days and were treated with glutathione-precursors and depletor, antibacterial agents, or sodium thiosulfate. The drug administered, the mortality, and the mean survival time were as follows: corn-oil controls (0), euthanatized at 25 days; AFB1-controls (2), 21 days; AFB1 and saline controls (2), 22 days; cysteine and AFB1 (5), 13 days; methionine and AFB1 (5), 12 days; sodium thiosulfate and AFB1 (2), 21 days; sulfadimethoxine and AFB1 (1), 24 days; oxytetracycline and AFB1 (0), euthanatized at 25 days; and ethyl maleate and AFB1 (3), 21 days. Clinical signs of toxicosis included decreased feed consumption during AFB1 administration, loss of body weight or failure to gain, and death. Clinicopathologic changes included increases in serum bilirubin concentration and alanine aminotransferase and aspartate aminotransferase activities. Prothrombin and activated partial thromboplastin times were lengthened. Plasma fibrinogen concentration was decreased. Changes in PCV, hemoglobin concentration, and serum alkaline phosphatase were unremarkable. Oxytetracycline had protective effects against chronic aflatoxicosis in rabbits. Cysteine and methionine enhanced chronic aflatoxicosis.

Topics: Aflatoxin B1; Aflatoxins; Animals; Blood; Blood Coagulation; Body Weight; Cysteine; Male; Maleates; Methionine; Oxytetracycline; Rabbits; Sulfadimethoxine; Thiosulfates

The LD50 of phencyclidine (PCP, 234 mumol/kg, i.p.) in male Swiss mice decreased by 62% in animals pretreated with 2-diethylamino-2,2-diphenylvalerate hydrochloride (SKF-525A, 40 mg/kg), and increased by 74% and 20% in animals pretreated with sodium phenobarbital (75 mg/kg), and 3-methylcholanthrene (70 mg/kg), respectively, No Significant change in the LD50 was observed with cysteine or diethylmaleate pretreatment. The treatment with PCP at 179 mumol/kg/day i.p. for 7 days resulted in body weight decrement in the first 2 days and gradual increment thereafter. The increase was only 33% of the control group. The food intake was also lower in the PCP treated group of animals. PCP withdrawal led to an increase in food intake as well as body weight at a normal rate. The ratio of liver weight to body weight was not significantly higher than that of control during the treatment period. The administration of PCP for 7 days did not alter the activities of liver function enzyme markers. However, within 12 h of the initial PCP treatment a 85% increase in activity of serum glutamicoxalacetic transaminase was observed. Later the enzyme activity reached close to normal levels. No liver lesions at the light microscopic level were observed. Treatment of mice for 4 days with PCP (179 mumol/kg) caused no significant change in pentobarbital sleeping time.

Topics: Animals; Body Weight; Cysteine; Eating; Lethal Dose 50; Liver; Male; Maleates; Methylcholanthrene; Mice; Microsomes, Liver; Pentobarbital; Phencyclidine; Phenobarbital; Proadifen