bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCDD causes stimulation of c‐ras expression in the hepatic plasma membranes in vivo and in vitro
Authors: Tullis Kathryn , Olsen Hugh , Bombick David W. , Matsumura F. , Jankun Jerzy 
Published: October 2006

AbstractA series of in vivo and in vitro experiments were conducted to determine the effects of 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin (TCDD) administered on the expression of c‐ras. Differences in c‐ras expression between control and TCDD treated groups were determined by immunoassay of p21ras protein, or indirectly measured by the specific binding of 3H‐GTP to hepatic plasma membrane preparations. Intraperitoneal injection of sublethal doses of TCDD significantly elevated (P < 0.05, Student t test) levels of hepatic p21ras protein in Sprague‐Dawley rats and TCDD sensitive C57BL/6J mice. Such an increase occurred at an early stage of poisoning in the C57BL/6J mice. The earliest increase was detectable 6 hr after dosing, and the differencebecame statistically significant by 12 and 24 hr after dosing. In contrast, TCDD tolerant DBA/2J mice had only a marginal increase in hepatic p21ras protein which did not become statistically significant even at 24 hr post‐dosing. TCDD evoked increases in hepatic p21ras protein of C57BL/6J mice were accompanied by the increase in the specific binding of GTP to hepatic plasma membranes. Column chromatography of solubilized rat hepatic membrane proteins on sephadex G‐50 showed TCDD administration increased levels of a 3H‐GTP binding protein with MW of approximately 21 Kd. 3H‐GTP binding in total hepatic membranes was also elevated (P<0.05, Fisher PLSD multiple comparison test) 6 hr and 24 hr after dosing of C57BL/6J mice, but as expected the effect of TCDD was not as conspicuous as that found in the plasma membrane. TCDD treatment increased levels of a 21 Kd protein found in the in vitro translation products of RNA purified from guinea pig liver. This protein was identified as a c‐ras protein based upon its ability to bind GTP, precipitation by a polyclonal antibody against the rasHa and Ki proteins and subsequent SDS‐PAGE which showed a single protein band of ≈ 21 Kd.
Autoionization reaction of phosgene (OCC12) studied by electron paramagnetic resonance/spin trapping techniques
Authors: Arroyo Carmen M. , Feliciano Felix , Kolb Dana L. , Keeler Jill R. , Millette Susan R. , Stotts Richard R. 
Published: October 2006

AbstractThe reaction of phosgene with ni‐trone spin traps was investigated using electron paramagnetic resonance (EPR)/spin trapping techniques. Evidence for the intermediacy of a carba‐moyl monochloride intermediate was obtained. Isotopic substitution of 13C‐phosgene was employed to verify the hyperfine coupling constant assignments. The implications of these observations on pulmonary damage caused by inhalation of phosgene are mentioned.
Characterization of cytochromes P450 in liver and kidney of rats treated with di‐(2‐ethylhexyl)phthalate
Authors: Okita Janice Rice , Castle Pamela J. , Okita Richard T. 
Published: October 2006

AbstractA polyclonal antibody was made to a liver cytochrome P450 purified from di‐(2‐ethyl‐hexy)Dphthalate (DEHP)‐treated Sprague‐Dawley rats and was used to identify the CYP4A forms in liver and kidney cortex microsomes of control rats and rats treated with this peroxisome proliferator. Three clearly separated major protein bands were recognized on western blots in liver microsomes of control male rats or male rats treated with a single dose of DEHP, which, based on the description of relative mobility, tissue specificity, and sex dependent expression of CYP4A forms (Sundseth and Waxman (1992). J. Biol. Chem., 267, 801–810), correspond to the migration pattern of forms 4A1, 4A2, and 4A3 in clofibrate‐treated rats. The administration of DEHP for 2 or 3 days caused a loss of resolution of two of the protein bands. The protein band corresponding to 4A2 was absent in liver or kidney cortex microsomes of DEHP‐treated or control female rats and was not always visible in the livers of control male rats. The purified P450DEHPsupported the hydroxylation of arachidonic acid at both the 19‐ and 20‐carbon atoms with turnover rates of 1.4×0.2 and 22.7×2.5 nmoles per minute per nmol P450, respectively. No measurable amounts of hydroxylated products were obtained when prostaglandin E1, leukotriene B4, or testosterone were used as substrates. Another member of the CYP4 family, 4B1 from rabbit lung microsomes, was also recognized by this antibody on western blot analysis; however, rabbit lung form 4A4 showed only minimal cross‐reactivity with this antibody.
Acute lindane intoxication: A study on lindane tissue concentration and oxidative stress‐related parameters in liver and erythrocytes
Authors: Junqueira V. B. C. , Bainy A. C. D. , Arisi A. C. M. , Azzalis L. A. , Simizu K. , Pimentel R. , Barros S. B. M. , Videla L. A. 
Published: October 2006

AbstractTreatment of rats with daily dosis of 20 mg of lindane/kg for 3 consecutive days led to the accumulation of the insecticide in several tissues, including erythrocytes and liver. Lindane did not alter the hematocrit and hemoglobin concentration but reduced methemogiobin levels by 17%. Red blood cells from controls and lindane‐treated rats, exposed to t‐butyl hydroperoxide, exhibited comparable rates of oxygen uptake and visible chemiluminescence, whereas the induction period that precedes oxygen uptake was significantly enhanced in the latter group. Lindane treatment did not modify the activity of erythrocyte glutathione peroxidase, glucose‐6‐phosphate dehydrogenase, catalase, and methemoglobin reductase, being the total content of glutathione and superoxide dismutase activity significantly increased. The liver from lindane‐treated rats showed an enhanced microsomal pro‐oxidant activity, evidenced by higher cytochrome P450 content and NADPH‐cytochrome c reductase and NADPH oxidase activities. The higher enzyme activities led to an increased superoxide anion generation (adrenochrome formation) and lipid peroxidation (measured either by the production of thiobarbituric acid reactants and spontaneous visible chemiluminescence). Concomitantly, liver glutathione content and the activity of glutathione peroxidase‐glutathione reductase couple were augmented by lindane treatment, without any change in superoxide dismutase activity, together with a reduction in that of catalase. Results suggest that lindane does not alter the prooxidant/antioxidant status of the erythrocyte in conditions of a significant cellular accumulation of the insecticide, which might exert direct action on enzymatic systems leading to enhanced superoxide dismutase activity and glutathione content. In the liver, lindane‐induced pro‐oxidant condition was not accompanied by cell injury, probably due to the adaptative increase in some antioxidant mechanisms of the hepatocyte.
Modulation of the rat hepatic cytochrome P450 composition by long‐term streptozotocin‐induced insulin‐dependent diabetes
Authors: Barnett Christopher R. , Flatt Peter R. , Ioannides Costas 
Published: October 2006

AbstractThe effects of long‐term insulin‐dependent diabetes on the enzymatic activities of hepatic cytochrome P450 isozymes were determined in rats rendered diabetic by the administration of streptozotocin and killed 4, 8, and 12 weeks following treatment. The O‐dealkylations of ethoxy‐resorufin and pentoxyresorufin were elevated in the diabetic animals throughout the study, the extent of increase being similar at all three time points. p‐Nitrophenol hydroxylase activity was induced in the diabetic animals 4 weeks following treatment with streptozotocin, but the extent of increase became less pronounced with the progress of the disease. A modest increase in ethylmorphine N‐demethylase activity was also observed but only in the diabetic animals killed 4 weeks after the induction of diabetes. Finally, lauric acid hydroxylase activity was elevated in the diabetic animals 4 weeks following streptozotocin administration but then declined rapidly with the duration of the disease. It is concluded that the duration of diabetes modulates the hepatic cytochrome P450 profile, with the effect being isoenzyme specific. Mechanisms that may account for these changes are discussed.
2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD)‐induced changes in glucose transporting activity in guinea pigs, mice, and rats in vivo and in vitro
Authors: Enan Essam , Matsumura Fumio 
Published: October 2006

AbstractThe toxic action of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) on glucose uptake was studied on different species, sexes, and strains of animals by using a nonmetabolizable glucose analog, 3‐0‐methyl D [1‐3H] glucose (3H‐Me‐glc). We have found a drastic reduction in glucose uptake in different organs from male guinea pigs in vivo as well as in vitro. Female guinea pigs were less responsive to this effect of TCDD compared to males. Highly TCDD‐responsive mice strains responded in the same way as the male guinea pigs, while less TCDD‐responsive mice strains did not. A reduction in glucose uptake was found in explant adipose tissue cultures (in vitro) of male mice (highly TCDD‐responsive) after a 4 hour incubation with 10−8 M TCDD. In less responsive mice strains, stimulation was observed using the same model (in vitro). In the case of male rats, as well as male guinea pigs, glucose uptake was highly reduced by 10−8 M TCDD using an in vitro system of explant adipose tissue. The Ah‐receptor blocker, 4,7‐phenanthroline, abolished the effect of TCDD on inhibition of glucose uptake in adipose tissue of male guinea pigs both in vivo and in vitro. Transcription and translation inhibitors (actinomycin D and cycloheximide, respectively) were tested separately or in combination with TCDD using the guinea pig adipose tissue culture model. It was found that actinomycin D could block the effect of TCDD on glucose uptake throughout the experiment time (360 min) while cycloheximide blocked TCDD action for about 60 minutes. Protein kinase inhibitors (e.g., genistein, neomycin) did not change the effect of TCDD on glucose uptake in male guinea pig adipose tissue. Based on these observations, we conclude that TCDD inhibits Me‐glc uptake in various organs in guinea pigs, mice, and rats, and this response is mediated by the Ah‐receptor.
Inhibition of S‐(1,2‐dichlorovinyl)‐L‐cysteine‐induced lipid peroxidation by antioxidants in rabbit renal cortical slices: Dissociation of lipid peroxidation and toxicity
Authors: Davis Joe W. , Petry Thomas W. 
Published: October 2006

AbstractPrecision‐cut, rabbit renal slices were used to examine the effects of three novel antioxidants (U‐74006, U‐74500, and U‐78517) on S‐(1,2‐dichlorovinyl)‐L‐cysteine (DCVC)‐induced lipid peroxidation and toxicity. Slices exposed to DCVC showed a dose‐ and time‐dependent increase in lipid peroxidation (TBARS) and a decrease in cellular viability, as evidenced by the loss of intracellular potassium, during the course of a 3 hour incubation. Subsequent studies employed DCVC concentrations of 100 μM. Microemulsion formulations of U‐78517, U‐74500, and U‐74006 (100 μM) inhibited DCVC‐induced lipid peroxidation by 100±, 50±, and <5% (not significant), respectively. However, none of these antioxidants had a significant effect on DCVC‐dependent cytotoxicity, as indicated by intracellular potassium release. The effects of U‐78517, the most potent of the three antioxidants, were similar to those observed with two model antioxidants, diphenyl‐p‐phenylenedi‐amine (DPPD) and the iron chelator, deferoxamine. Aminooxyacetic (AOAA), an inhibitor of renal cysteine conjugate β‐lyase, had only a minimal effect on DCVC‐induced lipid peroxidation, and no effect on toxicity.These data represent the first report of DCVC‐induced lipid peroxidation in rabbit renal cortical slices, a system which has been widely used to investigate mechanisms of nephrotoxicity, including that induced by DCVC. Our results demonstrate that DCVC‐induced lipid peroxidation in renal slices can be inhibited by a variety of antioxidant compounds operating by different mechanisms. Because inhibition of lipid peroxidation had minimal effect on DCVC‐dependent cytotoxicity, the data suggest that DCVC‐induced lipid peroxidation is not a major mechanism in the cytotoxicity induced by this compound.
Dioxygenase and Co‐oxidase activities of rat hepatic cytosolic lipoxygenase
Authors: Roy Sandip K. , Kulkarni Arun P. 
Published: October 2006

AbstractThe role of rat liver cytosolic lipoxygenase in the metabolism of benzidine was studied using linoleic acid as a cosubstrate. Under optimum assay conditions, cytosolic dioxygenase activity in the presence of 3.5 mM linoleic acid at pH 7.2 was 74.07 ± 1.43 nmoles/min/mg protein. Benzidine was oxidized at the rate of 3.18 ± 0.13 nmoles/min/mg cytosolic protein to benzidine diimine at pH 7.2 in the presence of 3.65 mM linoleic acid. Both dioxygenase and cooxidase reactions were inhibited by nordihydroguaiaretic acid in a concentration‐dependent manner. Partially purified preparations of rat liver lipoxygenase, free of hemoglobin, exhibited a dioxygenase activity of 223.1 ± 65.9 nmoles/min/mg protein and cooxidase activity of 6.1 ± 0.5 nmoles/min/mg protein toward benzidine. These results suggest that hepatic lipoxygenase may play an important role in the metabolism of this hepatocarcinogen.
2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD)‐induced reduction of adenosine deaminase activity in vivo and in vitro
Authors: Muralidhara  , Matsumura Fumio , Blankenship Alan 
Published: October 2006

Abstract2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) is a potent immunosuppressant in several animal species. The purpose of this study was to determine if TCDD affected the activity of adenosine deaminase (ADA), a purine metabolizing enzyme that is vital to the proper functioning of the immune system. The effect of TCDD on ADA ctivity was studied in various tissues of male Balb/c mice (a TCDD‐responsive strain) and DBA/2 mice (a less‐responsive strain). Of the tissues examined after administration of TCDD in vivo (115 μ/kg, i.p.), ADA activity was found to be significantly reduced in thymic and splenic tissues of Balb/c mice at 24 hours postadministration. The enzyme activity in these affected tissues remained consistently low through 10 days postadministration. Such an effect of TCDD was both dose and time related in the thymic tissue of Balb/c mice. In contrast, no appreciable alterations in ADA activity were evident in any of the tissues of DBA/2 mice at any of the sampling intervals, indicating that such an effect of TCDD is likely to be mediated through the Ah receptor.This in vivo effect of TCDD on thymic ADA activity was also reproducible in situ where isolated whole thymuses were directly incubated with 10 nM TCDD. In this model, TCDD's effects on ADA activity were antagonized by known protein kinase or phosphorylation inhibitors such as quercetin, genistein, tyrphostin, and neomycin. These results indicate that the effect of TCDD on ADA activity in the thymus may be related to its property to elevate protein kinase activities in this tissue. ADA activity was also reduced in 3T3 cells that were treated with 10 nM TCDD in a low (1%) serum media. In contrast, 25 ng/mL epidermal growth factor (EGF) under such conditions consistently stimulated ADA activity. Interestingly, EGF at a similar concentration failed to elicit a stimulatory effect on ADA activity when cells were pretreated with TCDD. The property of TCDD to lower ADA activity under in vivo, in situ, as well as in vitro conditions appears to be largely related to its action to modulate protein phosphorylation activities.
Urinary ascorbic acid—HPLC determination and application as a noninvasive biomarker of hepatic response
Authors: Poon R. , Chu I. , Lecavalier P. , Bergman A. , Villeneuve D. C. 
Published: October 2006

AbstractA high‐performance liquid chromatograph (HPLC) procedure has been developed for the determination of rat urinary ascorbic acid, a major metabolite cf the hepatic glucuronic acid pathway. The presence of EDTA and HC1 effectively inhibited degradation of ascorbic acid during the collection of urine specimens. The reliability of the procedure was demonstrated by its high recovery (90%), specificity (characteristic absorption maximum and discrimination from iso‐ascorbic acid), and reproducibility (2–3% coefficient of variation). The usefulness of this assay as an indicator of hepatic response was demonstrated in preliminary experiments where increases in urinary ascorbic acid excretion were detected in male rats treated with PCB 126 (3,3′,4,4′,5‐pentachloro‐biphenyl) or PCB 105 (2,3,3′,4,4′‐pentachlorobi‐phenyl). The HPLC measurement also showed that the two PCB congeners differed markedly in their potency in stimulating urinary ascorbic acid excretion. For example, 10 μ/kg bw/day of PCB 126 was sufficient to cause a fourfold increase in urinary ascorbic excretion while 5000 μ/kg bw/day of PCB 105 was required for a sevenfold increase. In response to the administration of PCB 105 or PCB 126, urinary ascorbic acid appeared to increase to the same extent as increases in hepatic ethoxyresorufin O‐deethylase (EROD) and UDP‐glucuronosyltransferase (UGT) activities, and to a much higher extent than changes in liver weight and hematological and serum clinical chemical parameters. The sensitivity and specificity, the ease in obtaining timed specimens, and the noninvasive nature make this assay a useful biomarker of hepatic response in dose‐finding and various acute and chronic studies.
Hepatic oxidative stress and related defenses during treatment of mice with acetylsalicylic acid and other peroxisome proliferators
Authors: Cai Yanong , Appelkvist Eeva‐Liisa , Depierre Joseph W. 
Published: October 2006

AbstractThe peroxisome proliferators perfluorooctanoic acid (PFOA; 0.02% w/w), perfluorodecanoic acid (PFDA; 0.02%, w/w), nafenopin (0.125%, w/w), clofibrate (0.5%, w/w), and acetylsalicylic acid (ASA; 1%, w/w) were administered to male C57 BL/6 mice in their diet for two weeks. Parameters for Fe3+ ADP, NADPH or ascorbic acid‐initiated lipid peroxidation in vitro were measured. Approximately a twofold increase in susceptibility to lipid peroxidation was obtained for all the peroxisome proliferators tested. Cotreatment of mice with the peroxisome proliferator ASA (1%, w/w) and a catalase inhibitor, 3‐amino‐1,2,4‐triazole (AT; 0.4%, w/w) for 7 days resulted in little inhibition of peroxisome proliferation, an elevated level of H2O2 in vivo, and total inhibition of the increased susceptibility to lipid peroxidation in vitro. No increase in lipid peroxidation in vivo was observed. Certain antioxidant enzymes (DT‐diaphorase, superoxide dismutase, glutathione transferase, glutathione peroxidase, and glutathione reductase) and components (ubiquinone and α‐tocopherol) were also measured. The results showed that there was some induction of these antioxidant enzymes and components by ASA or aminotriazole, except for glutathione peroxidase and superoxide dismutase, which were inhibited. The possible involvement of oxidative stress in the carcinogenicity of peroxisome proliferators is discussed.
The effects of hexachlorobenzene on circulating levels of adrenal steroids in the ovariectomized rat
Authors: Foster Warren G. , Mertineit Carmen , Yagminas Al , McMahon Avril , Lecavalier Pierre 
Published: October 2006

AbstractHexachlorobenzene (HCB), is a global pollutant that resists degradation and possesses a propensity to bioaccumulate. However, the effect of HCB on adrenal function remains largely unknown. Thus, circulating levels of adrenal steroids in HCB‐exposed (0.0, 1.0, 10.0, or 100.0 mg/kg/day—for 30 days by gavage) adult ovariectomized Sprague–Dawley rats (N = 32) were investigated. A terminal blood sample was collected for HCB residue analysis, and levels of circulating progesterone (P4), corticosterone (CS), and aldosterone (ALD) were quantified. Mean serum CS levels were significantly (P = 0.02) reduced by HCB exposure, starting with the lowest dose group (1.0 mg/kg/day for 30 days), whereas no differences in mean serum P4 and ALD levels were observed. Since it has been argued that the rodent possesses the ability to produce small amounts of cortisol and that levels of this glucocorticoid are altered in pathological states, serum cortisol (C) levels were also measured. Circulating levels of C were significantly lower (P < 0.05) in the highest dose group compared with controls. The presence of C in serum was confirmed by reverse‐phase HPLC. These data suggest that even at the lowest dose studied, HCB exposure induces alterations in steroidogenesis of cells of the adrenal cortex inner zone.
The anticarcinogen 3,3′‐diindolylmethane is an inhibitor of cytochrome P‐450
Authors: Stresser D. M. , Bailey G. S. , Williams D. E. , Bjeldanes L. F. 
Published: October 2006

AbstractDietary indole‐3‐carbinol inhibits carcinogenesis in rodents and trout. Several mechanisms of inhibition may exist. We reported previously that 3,3′‐diindolylmethane, an in vivo derivative of indole‐3‐carbinol, is a potent noncompetitive inhibitor of trout cytochrome P450 (CYP) 1A‐dependent ethoxyresorufin O‐deethylase with Ki values in the low micromolar range. We now report a similar potent inhibition by 3,3′‐diindolylmethane of rat and human CYP1A1, human CYP1A2, and rat CYP2B1 using various CYP‐specific or preferential activity assays. 3,3′‐Diindolylmethane also inhibited in vitro CYP‐mediated metabolism of the ubiquitous food contaminant and potent hepatocarcinogen, aflatoxin B1. There was no inhibition of cytochrome c reductase. In addition, we found 3,3′‐diindolylmethane to be a substrate for rat hepatic microsomal monooxygenase(s) and tentatively identified a monohydroxylated metabolite. These observations indicate that 3,3′‐diindolylmethane can inhibit the catalytic activities of a range of CYP isoforms from lower and higher vertebrates in vitro. This broadly based inhibition of CYP‐mediated activation of procarcinogens may be an indole‐3‐carbinol anticarcinogenic mechanism applicable to all species, including humans. © 1995 John Wiley & Sons, Inc.