bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of a S(trans‐1,2‐dichlorovinyl)‐L‐cysteine‐induced renal tubular toxicity by glutathione
Authors: Hassall C. D. , Brendel K. , Gandolfi A. J. 
Published: October 2006

AbstractThe nephrotoxin S‐(1,2‐dichlorovinyl)‐L‐cysteine (DCVC) is cleaved in the renal tubules to produce a reactive electrophilic intermediate. If this intermediate is responsible for the toxicity, addition of the nucleophilic scavenger glutathione (GSH) should decrease toxicity, and depletion of tubular GSH should enhance toxicity. GSH was added to isolated rabbit renal tubules simultaneously with, 15 min before, and 15 min after the addition of DCVC. The active accumulation of the organic anion para‐aminohippuric acid (PAH) and organic cation tetraethylammonium bromide (TEA) was used as an index of renal toxicity. Incubation of renal tubules with 0.01–1 mM DCVC for 15 min decreased active transport, with complete inhibition at 1 mM. This was accompanied by a 50% decrease in non‐protein sulfhydryl concentration. The addition of GSH (6 mM) simultaneously with DCVC completely prevented any decrease in active transport. The addition of GSH (6 mM) to tubules in which active transport was inhibited by DCVC reversed the inhibition to 80% of control. Similar enhancement of active transport occurred when tubules isolated 1 h after in vivo exposure to DCVC at 20‐100 mg kg−1 were incubated with GSH (6 mM). Preincubation of renal tubules with GSH (5‐15 mM) made them more refractory to the DCVC‐induced decreased PAH and TEA transport. The inhibition of active transport by DCVC is enhanced if the tubular non‐protein sulfhydryl is first lowered by diethyl maleate or glycidol. Thus, the tubular GSH concentration appears to be an integral component in regulating the alterations in active transport caused by DCVC.
Concurrent exposure of lead and manganese to iron‐deficent rats: Effect on lipid peroxidation and contents of some metals in the brain
Authors: Malhotra Kiran M. , Murthy R. C. , Srivastava R. S. , Chandra Satya V. 
Published: October 2006

AbstractIron‐deficient rats were co‐exposed to manganese and lead to study lipid peroxide formation and contents of lead, manganese, copper, iron, zinc and calcium in the brain. Concurrent exposure to lead and manganese increased the lipid peroxidation potential of brain in iron‐deficient rats. The concentration of lead, manganese and copper in the brain of iron‐deficient rats increased to a greater magnitude after concurrent exposure to manganese and lead, compared with that observed after the exposure of either of the metals alone. Since copper is a potent inhibitor of transport ATPase in the brain, its significant increase, coupled with increased lipid peroxidation in the brain of iron‐deficient rats, may be responsible for enhanced susceptibility of iron‐deficient rats to the neurotoxic effects after the combined exposure to lead and manganese.
Induction of electrophysiological and morphological changes in sprague‐dawley rats fed tributoxyethyl phosphate
Authors: Laham S. , Long G. , Schrader K. , Szabo J. 
Published: October 2006

AbstractThe effects of a widely used trialkyl phosphate (TP), tributoxyethyl phosphate (TBOP), on the peripheral nervous system of Sprague‐Dawley (SD) rats were investigated. Male and female SD rats were administered this chemical by gavage over a period of 18 weeks (low dose: 0.25 ml kg−1; high dose: 0.50 ml kg−1). Electrophysiological changes observed at 18 weeks in all test animals included a significant reduction (P<0.001) in nerve conduction velocity and an important increase (P<0.001) of both relative (RRP) and absolute refractory period (ARP). Light and electron microscopic examination of sciatic nerve from all test animals showed the presence of degenerating myelin sheaths accompanied by axonal swelling. An advanced stage of degeneration was indicated by the presence of lamellated electron dense inclusions in unmyelinated nerve fibres.
Lead in cerebrospinal fluid and its relationship to plasma lead in humans
Authors: Cavalleri A. , Minoia C. , Ceroni M. , Poloni M. 
Published: October 2006

AbstractLead levels in whole blood, plasma and cerebrospinal fluid (CSF) were determined in 18 patients suffering from Amyotrophic Lateral Sclerosis (ALS) and in 21 subjects hospitalized for neurological investigations. No significant differences were found for blood, plasma and CSF lead concentration between the ALS group and the other patient group. The plasma lead‐CSF lead mean ratio was greater than 1 in both groups, while in subjects with a slight degree of blood‐CSF barrier impairment a significant decrease of the ratio was demonstrated. A significant relationship between plasma lead and CSF lead levels (r=0.405; p<0.01), but not between whole blood lead and CSF lead levels, was established. Lead levels in CSF were also age‐related (r=0.485; p < 0.05) in the group of patients not suffering from ALS. In subjects with normal blood‐brain barrier permeability, lead in plasma is a good indicator of CSF lead concentration.
Toxicity of hexachlorocyclopentadiene: Subchronic (13‐week) administration by gavage to F344 rats and B6C3F1, mice
Authors: Abdo K. M. , Montgomery C. A. , Kluwe W. M. , Farnell D. R. , Prejean J. D. 
Published: October 2006

AbstractA 13‐week subchronic study was conducted by administering hexachlorocyclopentadiene (HCCP) in corn oil by gavage to groups of ten male and ten female F344 rats at doses of 150, 75, 38, 19, 10 or 0 mg kg−1, and to groups of ten male and ten female B6C3F1 mice at doses of 300, 150, 75, 38, 19 or 0 mg kg−1. The doses were administered once a day, five days per week for 13 weeks. Chemically induced deaths occurred at 150 and 300 mg kg−1 in rats and at 300 mg kg−1 in mice. A significant (P<0.05) depression in mean body‐weight change relative to controls was observed in male and female rats receiving ≥ 38 and ≥ 75 mg kg−1, respectively, and in male and female mice receiving 150 and 300 mg kg−1, respectively. There was a significant (P<0.05) increase in liver and kidney weight: brain weight ratios in the high‐dose female rats (75 and 150 mg kg−1) and female mice at all doses (19–300 mg kg−1). HCCP caused proliferative and inflammatory changes of the epithelia in the forestomach of male rats, and male and female mice receiving ≥ 38 mg kg−1 and in female rats receiving ≥ 19 mg kg dose level. Nephrosis characterized by proximal tubular dilation, cytoplasmic vacuolization, cytomegaly, karyomegaly and anisokaryosis occurred in male and female rats and female mice receiving ≥ 38 mg kg−1.
Pharmacodynamics and toxicity of chlorine in drinking water in the rat
Authors: Abdel‐Rahman Mohamed S. , Suh Duck H. , Bull Richard J. 
Published: October 2006

AbstractChlorine interacts with organic materials in surface water, leading to the formation of trihalomethanes, that may be carcinogenic. Studies were conducted to investigate the pharmacodynamics and toxicity of chlorine (0, 1, 10, 100 mg 1−1) in drinking water in rats. Blood glutathione (GSH) was significantly decreased after 6 months of treatment and this effect persisted after 1 year treatment in the 10 and 100 mg 1−1 groups. Treatment groups showed an increase in blood osmotic fragility. The acute study revealed that GSH was significantly decreased as early as 30 min after the administration of 30 and 120 μg chlorine. The effect was maintained up to 1 h. However, the GSH level returned to control value by 2 h. Blood osmotic fragility of the acute exposure was increased after 15 min and was without change after 30 min. Of the hematological parameters only the red blood cell count and hematocrit were significantly decreased in the 100 mg 1−1 group after 3 months of treatment. An examination of blood chloroform content in all the groups after 4, 6, 9 and 12 months showed no significant difference compared with the control. Chlorine administered chronically in drinking water for 3 months increased the incorporation of 3H‐thymidine into nuclei of rat kidney and testes in the 100 mg 1−1 group.
Mutagen formation in browning model systems
Authors: Shibamoto T. 
Published: October 2006

AbstractA browning model system, consisting of diacetyl and ammonia, produced frameshift and base‐pair substitution mutagens when the system was heated over 20 min and 120 min, respectively. The major product was 2,4,5‐trimethylimidazole, which showed no mutagenicity toward Salmonella typhimurium strains TA98 and TA100 with or without metabolic activation. When furfural was reacted with nitrate under mild conditions (for 30 min to 3 h at 0–25°C and pH 2–7), it did not produce mutagenic nitrofuran derivatives. However, the ethyl ether extract obtained from the reaction mixture of furfural and nitrate with hydrochloric acid exhibited strong mutagenic activities toward S. typhimurium strains TA98 and TA100 in the presence of metabolic activation. The major product of this reaction mixture, 4‐nitrofurfural, exhibited no mutagenicity toward tester strains TA98 and TA100 with or without metabolic activation. Pure active mutagen(s) was (were) not, however, identified in either system.
Hair mercury levels of Japanese women during the period 1881 to 1968
Authors: Suzuki Tsuguyoshi , Hongo Tetsuro , Yamamoto Reiko 
Published: October 2006

AbstractThe hair samples of Japanese females during the period from 1881 to 1968 were obtained from various localities of the central area of Japan. Inorganic mercury levels were elevated in unwashed hair samples from prewar periods, especially during 1920s, while elevation of organic mercury levels was conspicuous during 1960s. The increase of inorganic mercury levels in samples from the 1920s is suspected to be due to mercury contamination of hair cosmetics, and increased organic mercury levels in the hair from the 1960s can be explained by active fish consumption.
Application of a radioactivity detector to the analysis of 14C‐Carmoisine metabolites by ion‐pair high‐pressure liquid chromatography
Authors: Tragni E. , Costa L. G. , Marinovich M. , Galli C. L. 
Published: October 2006

Abstract14C‐Carmoisine was incubated under anaerobic conditions with a suspension of human faeces. Analyses of the incubation medium by high‐performance liquid chromatography (HPLC) attached to a radioactivity monitor (RAM) showed the same radioactivity profile as the urine and faeces of rats dosed with the same azodye (200 mg kg−1; 25 μCi). The analyses were carried out with a 5 μm RP‐C18 chromatographic column, using a linear gradient profile of different concentrations of water, methanol and an ion‐pair reagent. Five radioactive peaks were present in the radiochromatogram, in addition to unmodified Carmoisine. The major peak retained half of the specific activity of Carmoisine, and exhibited the retention time and the u.v. spectrum of authentic naphthionic acid. The results demonstrate the value and the advantage of using the in vitro preparation as a model to detect and to identify the metabolites of similar synthetic azodyes used as food additives.
The distribution of dermal tumorigens in coal liquids: Relationship of tumorigenicity and microbial mutagenicity
Authors: Holland J. M. , Larimer F. W. , Rao T. K. , Epler J. L. , Ho C.‐H. , Buchanan M. V. , Guerin M. R. 
Published: October 2006

AbstractPolycyclic aromatic hydrocarbons and/or their pyrolle derivatives were found to be the primary contributors to the skin tumorigenicity of the neutral fractions of two coal oils. Mutagenicity of the neutral fraction in Salmonella test strains was found to be due primarily to polycyclic aromatics containing polar substituents. Thus, the chemical classes responsible for skin tumorigencity differ from those responsible for mutagenicity.
Effect of intermittent carbon monoxide inhalation on erythropoiesis and organ weights in rats
Authors: Chen K. C. , Lee Eun Woo , McGrath James J. 
Published: October 2006

AbstractSprague–Dawley rats were exposed to 450 ppm carbon monoxide (CO) for 6h per day, 5 days per week for 33 days. The effect of CO on reticulocyte count, hematocrit, hemoglobin concentration, body weight and selected organ weights was measured. Exposure to CO caused a three‐fold increase in the youngest reticulocyte population, concomitant with an increase in the total reticulocyte count. Despite continued CO exposure, reticulocyte number and distribution returned to normal by day 9, suggesting that reticulocyte response of the organism to CO had changed. Both hematocrit and hemoglobin concentrations began to increase 16 days after CO exposure and remained at the increased level for the duration of the exposure period. There were no changes in kidney, liver and adrenal weights throughout the course of study. However, spleen weight was increased after 5 days of CO exposure. Left and right ventricular organ weight ratios increased equally at the same time during the study. These results indicate that the increase in the young reticulocyte population and the subsequent increase in total reticulocyte count are the earliest erythropoietic responses to intermittent CO exposure and that CO‐induced polycythemia is associated with cardiac hypertrophy in rats.
Mutagenicity and chemical characterization of two petroleum distillates
Authors: Carver June H. , Macgregor Judith A. , King R. W. 
Published: October 2006

AbstractTo investigate if the Salmonella/microsome assay could reliably screen complex petroleum samples for their carcinogenic potential, two high boiling (700–1070 °F) petroleum distillates with known activity in a dermal carcinogenesis bioassay were fully characterized with respect to their hydrocarbon composition and polynuclear aromatic hydrocarbon (PNA) content and assayed for mutagenic activity. Mutagenicity assays were also carried out on the aromatic hydrocarbon aggregates separated from these oils by adsorption chromatography. The composition of the distillates differed substantially, and reflected the fact that they were derived from crude oils that were extremely divergent in hydrocarbon character. Both the distillate and aromatic samples consistently induced a very slight increase in revertant TA98 and TA100 colonies; however, an increase of 2–4‐fold over background was observed when the S‐9 concentration was increased 5–10 times that of the standard assay. The maximal response was less than that expected from the samples' known PNA content and observed potency in the dermal carcinogenesis bioassay. In the Salmonella/microsome assay, all samples inhibited the mutagenic activity of added benzo[a]pyrene. Discordance between the magnitude of the samples' mutagenic activity and their known PNA content may be related to direct or indirect inhibition of sample PNAs by other components of the complex petroleum fractions. Observed inhibitory effects support the use of elevated S‐9 concentration in the in vitro assays assessing the carcinogenic potential of petroleum‐derived materials.
Studies on the mechanism of toxicity of the mycotoxin sporidesmin. 2—evidence for intracellular generation of superoxide radical from sporidesmin
Authors: Munday R. 
Published: October 2006

AbstractFormation of hydrogen peroxide, the dismutation product of superoxide radical, has been demonstrated in erythrocytes incubated with the mycoioxin sporidesmin. Erythrocytic thiols, both non‐protein and proteinbound, were depleted in the presence of sporidesmin, whilst haemoglobin was oxidized to methaemoglobin. Irreversible haemoglobin oxidation also occurred in these cells, shown by the formation of Heinz bodies; purified haemoglobin likewise suffered oxidative damage when incubated with sporidesmin in the presence of glutathione. Sporidesmin has previously been shown to generate superoxide radical in vitro; the erythrocytic changes induced by the mycotoxin, which are characteristically produced by compounds which generate ‘active oxygen’ species, suggest that it is also capable of generating this radical intracellularly.
Studies on the mechanism of toxicity of the mycotoxin sporidesmin 3—inhibition by metals of the generation of superoxide radical by sporidesmin
Authors: Munday R. 
Published: October 2006

AbstractThe mycotoxin sporidesmin has previously been shown to generate superoxide radical. This reaction involves autoxidation of the reduced form of the mycotoxin, a dithiol. In the present study, a number of mercaptide‐forming metals have been shown to inhibit superoxide formation from sporidesmin in vitro. Furthermore, these metals decreased the rate of sporidesmin‐induced hydrogen peroxide formation in erythrocytes and ameliorated the subsequent oxidative damage to these cells. These effects were found to be specific to sporidesmin; mercaptide‐forming metals did not inhibit the changes induced by compounds which are not dependent upon thiol groups for active oxygen generation. Zinc was one of the most potent inhibitors of superoxide generation from sporidesmin in these test systems; only mercury and cadmium were significantly more active. Salts of zinc are known to provide effective protection against the harmful effects of sporidesmin in vivo. The results of these studies provide a possible explanation for this effect.
A total hepatic induction index of metabolism for lipophilic xenobiotics
Authors: Boersma D. C. , Brownlee L. J. , Hollebone B. R. 
Published: October 2006

AbstractA model for monitoring the hepatic ability to metabolize lipophilic xenobiotics is proposed. By identifying the behaviour of the mixed‐function oxidase system as the rate determining feature of the response, an index can be devised from three independent factors: (i) the rate of the catalyzed reaction at each enzyme site, (ii) the concentration of such enzyme sites per hepatocyte and (iii) the total number of active hepatocytes available. Use of the model was tested by administering an acute oral dose of 1,2‐benzanthracene to Sprague‐Dawley rats. The above factors were measured in practical terms, these being (i) enzyme activity per time per mg protein, (ii) the concentration of enzyme per unit microsomal protein as well as the concentration of microsomal protein per unit liver weight and (iii) ratio of liver weight to body weight. After statistical analysis, it was found that each factor obeyed a different response curve characterized by a different ratio of growth to decay exponents. The product of these four measurable and physiologically discrete phenomena at any dose is the Total Hepatic Induction index. Together, the parameters that make up our model provide a means for inter‐ and intra‐species comparisons as a response to various chemicals.
Effect of temperature on the inhibition of rat brain synaptosomal ATPases by DDT and its structural analogs
Authors: Chetty Sreeramulu C. , Aldous Charles N. , Desaiah Durisala 
Published: October 2006

AbstractIn vitro effects of DDT and its isomers or metabolites were studied on Na+‐K+‐ATPase and oligomycinsensitive (OS) Mg++‐ATPase activities at 17, 27 and 37°C in rat brain synaptosomes. Dicofol and methoxychlor were found to be more effective inhibitors of Na+‐K+‐ATPase and OS Mg++‐ATPase than DDT, DDD and DDE. Inhibition of OS Mg++‐ATPase by the compounds tested (except DDE) was found to be greater at 17°C than at higher temperatures (17>27>37°C), suggesting a negative temperature correlation trend. Na+‐K+‐ATPase was less sensitive to these compounds when compared with OS Mg++‐ATPase and the inhibition was greater at higher temperatures (37>27>17°C), suggesting a positive temperature correlation trend. Other DDT isomers and metabolites showed variable effects on Na+‐K+‐ATPase and OS Mg++‐ATPases. DDD, but not DDE, inhibited both enzyme activities and the inhibition was independent of temperature. No significant differences were observed in the inhibitory potencies of the various DDT, DDD or DDE ring substitutes studied. The present data indicate that DDT, dicofol and methoxychlor were more effective inhibitors of OS Mg++‐ATPase than Na+‐K+‐ATPase and that the inhibition of the former enzyme had a negative temperature dependence, a feature which parallels toxicity results in insects.
A methylmercury toxicity model to test for possible adverse effects resulting from chelating agent therapy
Authors: Kostyniak P. J. , Soiefer A. I. 
Published: October 2006

AbstractA daily dosing model for methylmercury (MM) intoxication was developed for the purpose of testing for possible adverse effects resulting from the administration of complexing agents used in the treatment of MM poisoning. The dithiol complexing agents 2,3‐dimercaptopropanol (BAL) and meso‐2,3‐dimercaptosuccinic acid (DMSA) were chosen to test the discriminative ability of this model, since the former is contraindicated for MM poisoning and causes an increase in target organ MM burden, while the latter compound is known to be efficacious in reducing both toxicity and brain MM content. The basic design of the model called for daily observation of treated animals with identification of the following signs of MM intoxication: loss of body weight, onset of signs of toxicity, and mortality. The degree of toxicity was evaluated, and a toxicity score (0–5) was provided for each animal. A dose‐dependent decrease in body weight was found in MM‐treated mice. The latent period for development of signs of intoxication varied inversely with the dose rate. The rate of progression of severity of signs of intoxication was also dependent upon the dose. A dose rate of 14 mg Hg per kg per day was utilized to test the effects of BAL and DMSA on the onset and progression of signs of MM intoxication. Onset and progression of signs of methylmercury intoxication were similar for animals receiving methylmercury either alone or with administration of BAL at 2 mg per kg per day. Animals which received BAL at a dose rate of 20 mg per kg per day developed signs of intoxication significantly earlier. DMSA (500 mg kg−1) either alone or in combination with BAL (20 mg kg−1) protected animals against all signs of methylmercury poisoning. There was an insignificantly higher brain mercury concentration in animals receiving the 20 mg kg−1 BAL dose when compared to controls, whereas animals receiving the 500 mg kg−1 DMSA dose had brain concentrations one‐tenth that of matched control animals. The ability of DMSA to protect animals from the toxic effects of MM was confirmed, while BAL was shown to lack protective effects when given at the lower dose rate and to enhance MM toxicity when administered at the higher dose rate. This animal model of MM intoxication is useful in assessing both adverse and beneficial effects of new chelating agents on methylmercury intoxication.
Interaction of silicate dust with erythrocyte ghost membrane: In vitro studies
Authors: Singh Shivendra Vikram , Das Ballabh , Khan M. Firoze , Rahman Qamar 
Published: October 2006

AbstractComposition of the erythrocyte ghost membrane obtained from slate‐dust‐lysed and hypotonically lysed erythrocytes were compared in vitro. The protein and cholesterol contents were unaltered, whilst phospholipid and glycosamine contents decreased significantly in the slate‐dust‐lysed preparation of erythrocyte ghost membrane. Na+, K+‐ATPase activity remained unchanged, whilst acetylcholinesterase activity was decreased slightly by slate dust treatment. Further, binding of silicic acid, dissolving out of slate dust, was observed with a component of erythrocyte ghost membrane protein having molecular weight around 90 000 daltons. The significance of the findings is discussed.