bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early decreases in pulmonary, hepatic and renal glutathione levels in response to cadmium instillation into rat trachea
Authors: Iguchi Hiroshi , Ikeda Masayuki , Kojo Shosuke 
Published: October 2006

AbstractAfter instillation of cadmium (Cd) into the rat trachea, reduced and oxidized glutathione (GSH and GSSG) levels in the lung, liver and kidney were studied in relation to Cd concentrations and metallothionein (Mt) contents. Rats instilled with Cd developed haemorrhagic pneumonia, which deteriorated with a marked swelling of the lung throughout the experimental period of 48 h. The total glutathione (GSH + GSSG) level in the organs decreased after 6 h to 60–70% of the control levels. The decreased glutathione level was never restored to the control level within 48 h in the lung, and was possibly due to the pneumonia. Completely recovered glutathione was seen in other organs. The GSSG level did not decrease significantly in the lung or liver but lowered significantly after 12 h and 24 h. The GSSG fraction in the amount of total glutathione was 10% or more in the lung and 5% or less in the liver or kidney. This finding indicated that the total glutathione level was mainly changed by the decrease in the GSH fraction. Cadmium in the lung increased to 7.3 ppm 3 h after Cd instillation and decreased to 2.5 ppm within 48 h. Cadmium in the liver and kidney gradually increased with time, and after 48 h reached 1.1 and 2.3 ppm, respectively. This indicated a transportation of Cd from the lung to these organs. Moreover, the early stage of Cd accumulation coincided with the total glutathione decrease in the organs. After Cd instillation, pulmonary, hepatic and renal Mt started to increase at 3 or 6 h, and markedly increased at 24 h or later. After 48 h, the Mt concentration was similar in both the lung and liver, but was 2.5‐fold higher than in the kidney. These increases appeared to depend on the time that elapsed after Cd instillation, and not on the Cd concentration or glutathione level in each organ. It appears that Cd initially acted to decrease the glutathione level in the organs and then caused Mt synthesis, because the glutathione level was decreased at an early stage of Cd accumulation and preceded an apparent increase in Mt synthesis.
Metabolic aspects of the toxicology of mixtures of parathion, toxaphene and/or 2,4‐D in mice
Authors: Chaturvedi Arvind K. , Kuntz David J. , Rao N. G. S. 
Published: October 2006

AbstractThe effects of mixtures of parathion (PA; 5 mg kg−1), toxaphene (TOX; 50 mg kg−1) and/or 2,4‐dichlorophenoxyacetic acid (2,4‐D; 50 mg kg−1) on the hepatic mixed‐function oxygenase (MFO) system were studied in ICR male mice (21–24 g) by oral intubation daily for 7 days. In general, TOX and TOX‐containing mixtures were found to induce the metabolism of amidopyrine (21–52%), aniline (58–72%), phenacetin (239–307%), pentobarbital (104–148%) and benzo[a]pyrene (143–304%) in the 9000 g liver supernatants and to increase the hepatic cytochrome P‐450 contents (57–80%). Furthermore, the TOX pretreatemnt was effective in enhancing the biotransformation of PA or paraoxon (PO) in the supernatants. This enhancement was not altered significantly by 5 mM EDTA. Although TOX increased the aliesterase activity in the serum and liver homogenates and supernatants by 31–158%, the activity of paraoxonase was not affected in these preparations. The TOX‐induced increase in the metabolism of PA or PO was, at least in part, associated with the MFO system, and paraoxonase did not have significant involvement in the increase. These findings suggest that the toxicity of the PA + TOX mixture would be lower than that of PA, as TOX has the ability to increase the biotransformation of PA, as well as of PO, and the levels of aliesterase, thereby providing a pool of non‐critical enzymes for the binding of PO. Because of these properties of TOX, it is anticipated that the toxicity of the PA + TOX + 2,4‐D mixture also would be lower than that of PA.
Altered developmental toxicity caused by three carrier solvents
Authors: Rayburn J. R. , Deyoung D. J. , Bantle J. A. , Fort D. J. , McNew R. 
Published: October 2006

AbstractMany aquatic bioassays rely on chemical solvents to solubilize water‐insoluble test materials. Interactions between solvents and test materials can lead to false positive or negative results. For this reason, tests for interactions between solvents and test materials were performed. The Frog Embryo Teratogenesis Assay–Xenopus (FETAX) was chosen because of its capacity to assess three different endpoints; mortality, malformation and embryo growth. Three solvents–dimethylsulfoxide (DMSO), acetone and triethylene glycol (TG)–were tested with two teratogens–methylmercury chloride (MMC) and trichloroethylene (TCE). DMSO potentiated the lethal effect of both teratogens but did not alter significantly the rate of malformation. Acetone increased the mortality for both teratogens, but only increased the MMC malformation greater than the additive effects. TG only increased the mortality and malformation with TCE. There were additive effects for growth for all solvents with the teratogens. The carrier solvents caused interactions even at their no‐observable‐effect concentration (NOEC). Therefore, the choice of carrier solvent should be made with caution. This study shows that different results can occur depending on the solvent used, and that a difference in one endpoint does not necessarily change the other endpoints.
Possible involvement of 1,2‐diacetylbenzene in diethylbenzene‐induced neuropathy in rats
Authors: Gagnaire F. , Ensminger A. , Marignac B. , de Ceaurriz J. 
Published: October 2006

AbstractThe role of 1,2‐diacetylbenzene (1,2‐DAB) in the peripheral nerve toxicity of 1,2‐diethylbenzene (1,2‐DEB) was investigated in rats. Gas chromatography‐mass spectrometry identified 1,2‐DAB in the urine samples of rats given 165 mg kg−1 1,2‐DEB orally on four consecutive days. 1,2‐DAB shared not only the ability of 1,2‐DEB to cause bluish discoloration of skin, internal organs and urine, but unlike 1,2‐DEB it turned hair blue at the site of intraperitoneal injection.Intraperitoneal administration of 10 mg kg−1 and 20 mg kg−1 1,2‐DAB to groups of 12 rats, 4 days a week for 11 and 6 weeks, caused a dose‐ and time‐dependent decrease in mean sensory and motor conduction velocities. Recovery in a 5‐week post‐exposure period was gradual but consistent. The effect of 1,2‐DAB on the amplitude of the sensory action potential was ambiguous.The findings support the hypothesis that the formation of 1,2‐diacetylbenzene derivatives contributes to the neurotoxicity of 1,2‐DEB.
Influence of age and time of administration of dithiocarbamate analogues on cadmium retention in rats
Authors: Kargačin B. , Kostial K. , Arežina R. , Singh P. K. , Jones M. M. , Cikrt M. 
Published: October 2006

AbstractIn the present study the influence of age and time of chelation therapy on cadmium retention in 6‐, 11‐and 14‐day‐old rats and in 6‐week‐old rats has been investigated. Chelating agents N‐benzyl‐dithiocarboxy‐D‐glucamine (BDCG), sodium N‐(metho‐xybenzyl)‐D‐glucamine dithiocarbamate monohydrate (MeOBDCG) and N‐methyl‐N‐dithiocarboxy‐D‐glucamine (MDCG) were administered intraperitoneally to three different groups at a dose of 1 mmol kg−1 body weight on two occasions following 115mCd intraperitoneal administration; immediately and after 24 h; after 24 h and 48 h; or after 48 h and 72 h. The 115mCd retention in the whole body and organs was determined 6 days after cadmium administration. Chelation therapy very effectively reduced cadmium retention in the whole body and organs, MeOBDCG being the most effective. The effects of chelating agents were significantly more pronounced in older than younger animals and in the case of early rather than late administration. The highest fraction of cadmium administered was retained in the liver, where also the strongest effect of chelation therapy was observed. Mobilized cadmium was excreted almost exlusively by the faecal route.
Ni3S2 uptake by lung cells and its interaction with plasma membranes
Authors: Shirali P. , Decaestecker A. M. , Marez T. , Hildebrand H. F. , Bailly C. , Martinez R. 
Published: October 2006

AbstractThe uptake and biological transformation of Ni3S2 was studied on guinea pig alveolar macrophages (GPAM) in primary culture. Two different pathways are observed: (i) phagocytosis of αNi3S2 crystals and subsequent degradation to minute particles, which are recovered bound to the membranes of phagocytic vacuoles and to lysosomal membranes. These degradation products contain sulphur in very reduced quantities, as revealed by energy‐dispersive spectrometry (EDS). (ii) Extracellular degradation to regular round particles (0.1–0.2 μm) and irregular minute particles (10–30 nm). Round particles may enter the cell by pinocytosis and are characterized by the loss of sulphur. Minute particles are bound preferentially to cell membranes, to cytoplasmic organelles, such as endoplasmic reticulum, mitochondria and peroxysomes, to liposomes and to the euchromatinic part of nuclei. EDS analyses in these particles revealed the substitution of sulphur by phosphorus. This observation suggests the formation of an Ni–P complex with the phosphate groups of membranous and liposomal phospholipids and of the euchromatinic part of DNA or RNA. Steady‐state flourescence polarization analysis were carried out on GPAM and, for comparative purposes, on human embryonic pulmonary epithelial cells (L132 cell line). In both cell types they revealed a significant increase of membrane fluidity, induced either by desaturation of aliphatic chains or directly by the cleavage of fatty acid chains.
Carcinogenic effects of Bis(2,3‐dibromopropyl)‐phosphate in wistar rats
Authors: Takada Koichi , Naito Katsushi , Kobayashi Kazuo , Tobe Masuo , Kurokawa Yuji , Fukuoka Masamichi 
Published: October 2006

AbstractFour groups of 40 Wistar rats of each sex per dose level were fed diets containing 0, 80, 400 or 2000 ppm of the magnesium salt of bis(2,3‐dibromopropyl)phosphate (Bis‐BP) for 24 months. A high incidence of tumours was induced, in both sexes, in the digestive system. Tumours included papillomas and adenocarcinomas of the tongue, oesophagus and forestomach, adenocarcinomas of the intestine and hepatocellular adenomas (neoplastic nodules) and carcinomas. Pre‐terminal mortalities were associated with an increased incidence of forestomach papillomas in both sexes, adenocarcinomas of the small intestine in male rats and increased incidence of hepatocellular carcinomas in females. The data suggest that Bis‐BP is a more potent proximate carcinogen than tris‐(2,3‐dibromopropyl)phosphate (Tris‐BP).
Copper‐induced non‐selective permeability changes in intracellularly perfused snail neurons
Authors: Kiss Tibor , Györi János , Osipenko Oleg N. , Maginyan Silva B. 
Published: October 2006

AbstractThe effect of extracellularly applied Cu2+ was studied on isolated intracellularly perfused Helix pomatia neurons. It was found that the Cu2+‐activated current (ICu) is biphasic and composed of overlapping outward and inward components. The outward component of ICu is the result of a blockade by Cu2+ of the steady‐state outward Cl− current. The inward component is assumed to flow through Ca2+‐activated non‐selective cationic channels. The washing‐out procedure resulted in a large inward current (Iw), which was composed of transient and steady‐state components. It is most likely that the activation of metabolic pumps is responsible for the transient component and the steady‐state component is the result of increased neuronal membrane permeability for Cl−. Moreover, both ICu and Iw were highly Ca2+ ‐ and temperature‐dependent processes. It is concluded that Cu2+ application resulted in complex permeability changes in the Helix pomatia neurons.
Cadmium accumulation in the lung, liver and kidney of mice and rats chronically exposed to cigarette smoke
Authors: Gairola C. Gary , Wagner George J. 
Published: October 2006

AbstractCigarette smoking constitutes a major source of cadmium exposure via inhalation in man. To determine how smoke exposure affects the organ distribution and accumulation of cadmium, male C57B1 mice and Sprague‐Dawley rats were exposed daily for 52–60 consecutive weeks to mainstream smoke from the University of Kentucky reference cigarettes (2R1) in a nose‐only exposure system. Exposed mice and rats averaged blood carboxyhemoglobin values of 17.7 and 7.2%, and a daily total particulate matter (TPM) dose of 7.2 and 3.2 mg kg−1 body wt. per exposure, respectively. These results suggested effective inhalation of smoke by the animals. The tissues were acid digested and analyzed for cadmium by atomic absorption spectrometry. Cadmum levels 5–6‐ and 2–3‐fold greater than control levels were detected in the lungs and kidneys, respectively, of exposed animals of both species. In contrast, the liver did not show increased cadmium levels in exposed mice or rats. The data suggest that low‐dose chronic inhalation exposure to cigarette smoke leads to highest cadmium accumulation in the lung, followed by the kidney, with minimal effects on cadmium levels in the liver.
Application of alkaline unwinding to analysis of strand breaks induced by bleomycin in hamster lung DNA in vivo
Authors: Huff Robin A. , Bevan David R. 
Published: October 2006

AbstractStrand breaks in hamster lung DNA were analyzed following in vivo exposure to bleomycin. An alkaline unwinding procedure involving separation of single‐strand from double‐strand DNA by hydroxylapatite chromatography followed by fluorescence detection of DNA with bisbenzimide was adapted for these studies. Procedures were developed that allowed preparation of DNA from lungs of control animals with a relatively low amount of single‐strand DNA relative to double‐strand DNA. Time dependence of unwinding was demonstrated using samples that were damaged deliberately by brief probe sonication. To verify that residual bleomycin remaining in lungs at the time of sacrifice did not cause strand breaks during sample preparation, bleomycin was added to minced lung in vitro. Under these conditions, the ratio of single‐strand to double‐strand DNA was not increased significantly. Substantial strand breaks were produced in vivo at 15 min and 1 h following intratracheal instillation of bleomycin into hamsters, as evidenced by a 5–6‐fold increase in the ratio of single‐strand to double‐strand DNA relative to controls. The DNA damage appeared to be repaired within 1 day following exposure.
Diurnal exposure profile in rats from dietary administration of a chemical (doxazosin) with a short half‐life: Interplay of age and diurnal feeding pattern
Authors: Charuel C. , Comby P. , Monro A. M. 
Published: October 2006

AbstractDoxazosin, an α‐adrenergic blocking agent, has a plasma half‐life in male rats of 1–2 h after i.v. administration. Plasma concentrations of doxazosin were measured in male rats receiving the drug mixed in the diet at dose levels from 5 to 40 mg kg−1. Samples taken at 4‐h intervals during the light (0700–1900) and dark phases revealed peak concentrations at 0400 which were only about three times higher than the trough concentrations observed ca. 12 h later. The 24‐h area under the curve (AUC) values increased disproportionately with dose and with age from 2 months up to 8 months of age; thereafter they were fairly stable to 24 months of age. This age‐related effect may have been due to a reduction in clearance and/or a change in the feeding pattern of the rats. Young rats consumed ca. 84% and old rats only 45% of their daily feed during the nocturnal (active) phase. Given the known diurnal rhythms in absorption, protein binding and enzyme metabolising activity, such a change in feeding pattern with age may have wider toxicokinetic implications.
Review of chemical and uv light‐induced melanomas in experimental animals in relation to human melanoma incidence
Authors: Ingram Andrew John 
Published: October 2006

AbstractIn a few epidemiological studies on oil refinery workers, a slight excess of melanoma incidence has been reported. To see if this might be linked to exposure to polycyclic aromatic hydrocarbons (PAHs) contained in refinery streams, a review of animal data on the relationship between PAH exposure, UV light and melanoma induction has been carried out and compared with human data.This revealed that the highly carcinogenic PAH 7,12‐dimethylbenz[a]anthracene (DMBA) was capable of inducing melanomas in hamsters, mice and guinea pigs, but only under certain experimental conditions. Evidence suggested that other carcinogenic PAHs were unable to induce melanomas. As high dose levels of DMBA were generally required to produce melanomas, it was not considered that the amounts present in refinery streams would be sufficient to account for an increase in melanoma incidence in exposed workers.This conclusion was substantiated by the failure of petroleum‐derived complex hydrocarbon mixtures to produce melanomas in animals or man and by drawing attention to the absence of any association between melanoma incidence and the incidence of other skin cancers in man. If PAHs were responsible for an increase in melanoma incidence, an increase in other skin tumours would also be expected.It was concluded that animal data, taken in conjunction with other information, do not suggest that PAH exposure is likely to be the cause of any elevation in melanoma incidence in refinery workers. More detailed epidemiological findings would be required to establish whether any excess incidence of melanomas was due to sunlight, other risk factors or chance occurrences.
Inhalation exposure of rats to metal aerosol. II. Study of mutagenic effect on alveolar macrophages
Authors: Chorvatovičová Darina , Kováčiková Zuzana 
Published: October 2006

AbstractThe effects of inhalation exposure to metal aerosol derived from nickel refinery waste were studied on the frequency of chromosome aberrations in alveolar macrophages in Wistar rats. A 4‐month exposure period resulted in significant (P < 0.01) increases in chromosome aberrations. Relatively high variability without statistical significance was observed after a 4‐week exposure period. Increase in damaged alveolar macrophages with the length of exposure seems to point to the role of pulmonary metal deposits. Comparison of the results with those found after 6 months of exposure in bone marrow cells confirmed that metal particles in nickel refinery waste are genotoxic. Thus, this study indicates that alveolar macrophages are suitable for monitoring the genotoxic potential of hazardous chemicals administered by inhalation.
Use of hair analysis for evaluating mercury intoxication of the human body: A review
Authors: Katz Sidney A. , Katz Roya B. 
Published: October 2006

AbstractRelationships have been established between the concentrations of mercury in human scalp hair and environmental or dietary mercury exposures. For chronic exposures, the hair/blood ratio for mercury is in the range 200:1–300:1, and scalp hair mercury concentrations of >5 ppm are indicative of mercury intoxication. These observations, coupled with the ease by which samples may be collected, transported and stored, support the use of hair analysis for evaluating mercury intoxication of the human body.
Efficacy of hydrated sodium calcium aluminosilicate in reducing the toxicity of dietary zearalenone to mink
Authors: Bursian S. J. , Aulerich R. J. , Cameron J. K. , Ames N. K. , Steficek B. A. 
Published: October 2006

AbstractOvariectomized mink were fed diets containing zearalenone (ZEN) at concentrations of 0, 10 or 20 ppm with or without 0.5% hydrated sodium calcium aluminosilicate (HSCAS) for 24 days. Zearalenone at 10 and 20 ppm caused a significant increase in uterine weights, while 20 ppm ZEN resulted in significantly higher vulva swelling scores when compared to controls. The presence of HSCAS in the diet did not alter these hyperestrogenic effects of ZEN. In a second experiment, female mink were provided diets containing 20 ppm ZEN, 20 ppm ZEN plus 0.5% HSCAS or a control diet from 1 January 1989 through whelping (25 April to 15 May 1989). The females were given an opportunity to mate with untreated proven breeder males beginning on 1 March (day 59 of exposure). ZEN did not have an effect on the number of females whelping but there was a significant increase in gestation length, a decrease in litter size and an increase in kit mortality from birth to 3 weeks of age when compared to the control group and the group receiving the combination of ZEN and HSCAS. These results suggest that HSCAS can alleviate some of the reproductive effects of ZEN which are not related to its estrogenic action.
Effects of dibutyrylcyclic adenosine monophosphate on bleomycin‐induced lung toxicity in hamsters
Authors: O'Neill Charles A. , Giri Shri N. , Wang Qingjian , Perricone Michael A. , Hyde Dallas M. 
Published: October 2006

AbstractCyclic nucleotides play an important role in the regulation of fibroblast proliferation and collagen metabolism. In the present study, the antifibrotic potential of dibutyrylcAMP (Bt2cAMP) was evaluated in the bleomycin (BLM)‐hamster model of pulmonary fibrosis. Bt2cAMP (10 mg kg−1, s.c.) or saline (SA, s.c.) was given daily two days prior to the first intratracheal (i.t.) dose of BLM or SA and thereafter throughout the study. BLM or SA was instilled i.t. in three consecutive doses (2.5, 2.0 and 1.5 U 5ml−1 kg−1) at weekly intervals. Hamsters were killed at 7, 14 and 20 days after the third i.t. instillation. Bt2cAMP significantly reduced the contents of lung hydroxyproline and lung thiobarbituric acid reactive substance equivalents in BLM‐treated animals at 7 and 14 days. Bt2cAMP significantly elevated lung superoxide dismutase activity in BLM‐treated animals at 7 days. Lung prolyl hydroxylase activity was significantly elevated at 14 and 20 days in SABLM‐ and Bt2cAMPBLM‐treated animals. The ratio of cAMP/cGMP was significantly reduced at all tone points in SABLM‐treated animals but only at 7 and 14 days in Bt2cAMPBLM‐treated animals. Bt2cAMP caused no significant changes in lung calcium and calmodulin levels and protein content of the bronchoalveolar lavage. BLM significantly increased various inflammatory cell counts in the lavage at all three time points. The cell counts in the Bt2cAMPBLM groups were generally lower at 7 days and higher at 20 days than those of the SABLM groups. Histological evaluation showed that the lungs of Bt2cAMPBLM‐treated hamsters progressed from an inflammatory cell lesion to a fibrotic lesion at a slower rate than the SABLM groups. It was concluded that Bt2cAMP attenuated BLM‐induced pulmonary fibrosis in hamsters in part by delaying the acute phase of the inflammatory reaction.