bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beryllium‐induced biochemical alterations and their prevention following Co‐administration of Meso‐2,3‐dimercaptosuccinic acid or 2,3‐dimercaptopropane sulphonate in rats
Authors: Mathur Seema , Mathur R. , Flora S. J. S. , Kannan G. M. , Gupta S. Das 
Published: October 2006

AbstractThe effects of meso‐2,3‐dimercaptosuccinic acid (DMSA) and 2,3‐dimercaptopropane sulphonate (DMPS) on body beryllium burden, hepatic lipid peroxidation, glutathione, alkaline and acid phosphatase and some biochemical variables of porphyrin metabolism were studied in beryllium‐poisoned rats. It was observed that beryllium poisoning is associated with a slight increase in lipid peroxidation, significant depletion of alkaline phosphatase and elevation of acid phosphatase activities in the liver and increased beryllium concentration in blood and other soft organs. Evidence is presented that both DMSA and DMPS during concomitant administration prevented most of the above beryllium‐induced biochemical alterations. Tissue beryllium concentration and histopathological lesions in liver and kidneys were also significantly less marked following simultaneous administration of DMPS compared to beryllium‐exposed controls; DMSA was comparatively less effective.
Autometallographic detection of silver in hypothalamic neurons of rats exposed to silver nitrate
Authors: Stoltenberg Meredin , Juhl Søren , Poulsen Elin Hyldgaard , Ernst Erik 
Published: October 2006

AbstractThe silver amplification technique, autometallography, has been used to reveal silver accumulation in neurons in the hypothalamus of male Wistar–Kyoto rats. Silver penetrated the blood‐brain barrier after exposure to silver nitrate, and differences in staining intensity were found between the hypothalamic nuclei. When using light microscopy, the silver staining of the hypothalamic neurons was highly heterogeneous. Silver was detected exclusively in lysosomes of the loaded neurons. Aspects of this heterogeneous localization are discussed in relation to the distribution of autometallographically developed gold and mercury.
Urinary enzyme excretion as a parameter for detection of acute renal damage mediated by N‐(3,5‐dichlorophenyl)succinimide (NDPS) in fischer 344 rats
Authors: Valentovic Monica , Williams Pamela , Iii John Carl , Rankin Gary O. 
Published: October 2006

AbstractThe kidney has been identified as the specific target organ for in vivo exposure to an agricultural fungicide, N‐(3,5‐dichlorophenyl)succinimide (NDPS). The goal of this study was to determine if urinary protein and enzyme excretion were sensitive, non‐invasive markers for NDPS‐induced renal damage. The proximal tubular enzymes that were monitored were the brush‐border enzyme alkaline phosphatase (ALP) and the lysosomal enzyme N‐acetyl‐β‐D‐glucosaminidase (NAG). Male Fischer 344 (F344) rats were injected intraperitoneally (i.p.) with 0.2 or 1.0 mmol kg1 NDPS. Control animals were injected i.p. with sesame oil (2.5 ml kg−1). Urine was collected on ice 0–3, 3–6 and 6–24 h after NDPS or vehicle injection. Urinary protein and urinary NAG excretion levels were elevated (P < 0.05) above the control levels 0–3 h after treatment with 0.2 mmol kg−1 NDPS. Urinary protein and enzyme excretion was comparable between 0.2 mmol kg−1 NDPS‐treated and control groups for all other time periods. Administration of a marked nephrotoxicant dose (1.0 mmol kg−1) was associated with elevated levels of urinary protein, NAG and ALP beginning 0–3 h after treatment when compared to the control group or to respective baseline values. It was concluded from these studies that measurement of urinary protein as well as the release of ALP and NAG were sensitive markers of renal damage produced by NDPS.
Liver lipid peroxidation and glutathione‐related defence enzyme systems in mice treated with paracetamol
Authors: Özdemirler Gül , Aykaç Gülçin , Uysal Müjdat , Öz Hikmet 
Published: October 2006

AbstractGlutathione levels were found to be decreased while lipid peroxide levels were increased in total liver homogenates 6 h following paracetamol treatment (500 mg kg−1 i.p.). Furthermore, it has been determined that cytosolic glutathione S‐transferase (GST) activity was decreased and glutathione peroxidase (GSH‐Px) activity remained unchanged. On the other hand, a decrease in liver microsomal lipid peroxide levels and an increase in GST and GSH‐Px activity has been observed. We concluded that decreased lipid peroxide levels in microsomes could be a consequence of increased GSH‐Px and GST enzyme activities. In this way, these glutathione‐related defence enzyme systems may play an important role in protecting microsomes from lipid peroxidation.
Review of oximes available for treatment of nerve agent poisoning
Authors: Dawson R. M. 
Published: October 2006

AbstractA review was conducted of papers describing the use of N‐methyl‐2‐pyridinealdoxime (PAM), toxogonin or HI‐6 as antidotes to the nerve agents tabun, sarin, soman and VX. The review included use of the oxime alone, oxime plus atropine and oxime plus atropine plus diazepam, given therapeutically, i.e. after nerve agent, in all cases. Experiments with any of these compounds given prophylactically were not considered. The review also included protocols of pyridostigmine prophylaxis and oxime‐atropine therapy (with or without diazepam). It was difficult to draw conclusions as to the best oxime to use, because of lack of data in many cases. The identity of the oxime did not appear to be important when pyridostigmine prophylaxis was combined with atropine‐oxime‐diazepam therapy; in these cases, very good protection was observed in guinea pigs against all four nerve agents. The choice of oxime based on the data presently available may well depend on factors other than protection against lethality, such as cost and availability of the oxime and human toxicity of the oxime. This last factor was also reviewed, and the results showed that toxogonin is likely to cause more side‐effects than PAM or HI‐6. The efficacy of the oximes against the emerging threat agent GF was also reviewed.
Chromium‐induced micronuclei in fish
Authors: Al‐Sabti K. , Franko M. , Andrijanič B. , Knez S. , Stegnar P. 
Published: October 2006

AbstractAn investigation of the cytogenetic effects of chromium (Cr(VI) and Cr(III)) in Prussian carp (Carassius auratus gibelio) was made. For detecting cytogenetic damage, micronuclei induction in fish erythrocyte cells was employed. Fish were investigated 100 m above and 400 m below the discharge of leather waste products into the river Ljubljanica, and by exposing fish to three doses of chromium (Cr(VI) and Cr(III)) in the laboratory. The exposure of fish to various concentration levels (sub‐lethal) of chromium under laboratory and field conditions caused an increase in the frequency of micronuclei compared with the control groups.
Teratological assessment of stobadine after single and repeated administration in mice
Authors: Ujházy E. , Dubovický M. , Balonová T. , Janšák J. , Zeljenková D. 
Published: October 2006

AbstractTeratological studies were performed with stobadine, a compound with antiarrhythmic and antihypoxic activity. Single i.v. injections of stobadine in the form of dihydrochloride (DH 1011) to ICR mice on days 3, 6, 9 or 12 of gestation at doses of 1 and 3 mg kg−1 had no teratogenic effect. Slight fetal toxicity was manifested by decreased fetal weight after treatment on days 3 and 6, increased incidence of rudimentary ribs after treatment on days 9 and 12 of gestation and non‐significantly increased postimplantation loss after injection on day 6 of gestation. The effect of repeated oral administration in the form of dipalmitate salt (DP 1031) was studied in doses of 12.2, 61.0 and 122.0 mg kg−1 on days 4–16 of gestation. Oral exposure to 61.0 mg kg−1 DP 1031 resulted in significant reduction of implantations, live fetuses and litter weight, and after 122.0 mg kg−1 DP 1031 the fetal weight was significantly decreased. External and skeletal examinations of the fetuses revealed no evidence of teratogenesis. The relevance of the two routes of stobadine administration for risk involvement is discussed.
Method for preserving erythrocytic δ‐aminolevulinic acid dehydratase activity that facilitates population studies on lead intoxication
Authors: Burns C. B. , Sriprakash K. S. , Powers J. R. , Currie B. J. 
Published: October 2006

AbstractA method preserving the activity of the erythrocytic enzyme α‐aminolevulinic acid dehydratase (EC 4.2.1.24) was developed using a vehicle of 50% aqueous glycerol containing dithiothreitol (80 μM). Whole heparinized blood (0.5 ml) was added to 0.75 ml of this mixture in a cryovial tube (capacity 1.3 ml), mixed well and stored in a freezer at −20°C for 21 days. Statistical comparison of the enzyme activity when freshly assayed and after storage indicated excellent agreement for quantitation of the non‐activated enzyme (intraclass correlation coefficient = 0.99) and the activated enzyme (intraclass correlation coefficient = 0.98). This storage method will facilitate future population studies on lead intoxication, particularly those in remote locations.
Ex vivo technique for evaluating the effect of chemical vapours on mucociliary activity
Authors: Bonnet P. , Nunge H. , Gagnaire F. , Zahm J. M. 
Published: October 2006

AbstractAn experimental protocol has been developed for the use of rat tracheal explant to evaluate the effects of inhaled chemicals on the mucociliary function. Rats were exposed for 4 h or 7 days (24 h per day) to different concentrations of toluene diisocyanate (TDI). Each rat trachea was subsequently removed rapidly and placed in a humid chamber maintained at 37°C. Mucociliary function was evaluated by video measurements of the two following parameters: mucociliary beating frequency (MCBF) and number of active (A+), partially active (A−) and inactive areas (A−).In control tracheas, all areas were active and the MCBF showed hardly any variation around 15.3 Hz. In rats exposed to ca. 0.27 or 0.54 ppm of TDI for 4 h, tracheas showed a significant decrease in the number of active areas and a significant decrease in the MCBF. The same changes were observed in tracheas from rats exposed to approximately 0.05 and 0.10 ppm of TDI for 7 days. After a 7 day recovery period the number of active areas and the MCBF were similar in exposed and control rats except in the group exposed for 7 days to the highest concentration; these showed only partial recovery. The results of this study showed that this ex vivo method is useful for detecting mucociliary dysfunction.
Oxidant radical release by alveolar macrophages after cadmium chloride exposure in vitro
Authors: Leduc D. , Gressier B. , Gosset Ph. , Lheureux Ph. , De Vuyst P. , Wallaert B. , Yernault J. C. 
Published: October 2006

AbstractChronic exposure to cadmium can cause lung emphysema, the mechanism of which is unknown. Current concepts on the pathogenesis of emphysema largely emphasize the role of a protease‐antiprotease imbalance. The aim of this work was to study the effects of cadmium on the regulation of antiprotease activity and the release of oxidant radicals from alveolar macrophages.Guinea pig alveolar macrophages (AM) were exposed overnight to cadmium chloride (CdCl2) in vitro. To define the cytolytic threshold dose, cell lysis was evaluated by trypan blue exclusion and lactate dehydrogenase release. Non‐cytolytic concentrations were then used (0.1, 0.4 and 0.8 ppm) to simulate chronic exposure conditions. Overnight exposure to 0.1, 0.4 and 0.8 ppm CdCl2 decreased intracellular ATP (mean ± SD: 91 ± 8%, 72 ± 7%, 50 ± 8% of control cells, respectively), suggesting that even at non‐cytolytic doses, Cd2+ can cause cell injury. The assessment of oxygen radical release from AM after overnight exposure to CdCl2 showed a dose‐dependent decrease to 54.3 ± 8.2%, 32.2 ± 4.3% and 25 ± 3% of control after exposure to 0.1, 0.4 and 0.8 ppm Cd2+, respectively. At non‐cytolytic concentrations (0.1, 0.4 and 0.8 ppm) CdCl2 did not decrease α1‐proteinase inhibitor activity either in the absence of AM or in the presence of AM and myeloperoxidase.In conclusion, our in vitro results do not suggest that a protease‐antiprotease imbalance is involved in the pathogenesis of cadmium‐induced emphysema. However, these data should be considered in the context of an eventual increase of protease burden in the lung caused by the migration of neutrophils and macrophages into the alveolar space after CdCl2 exposure in vivo. Cadmium, by impairing the release of oxidant radicals from AM, may increase susceptibility to respiratory infections.
Time‐dependent effects of lead on rat reproductive functions
Authors: Kempinas W. G. , Favaretto A. L. V. , Melo V. R. , Carvalho T. L. Lamano , Petenusci S. O. , Oliveira‐Filho R. M. 
Published: October 2006

AbstractThe effects of exposure to lead on endocrine function and the reproductive parameters were studied in pubertal rats treated with 1.0 g l−1 lead acetate in drinking water for 20 days (subacute group) or 9 months (chronic group) in addition to i.v. injections of lead acetate (0.1 mg 100 g−1 body wt.) every 10 (subacute group) or 15 days (chronic group). Although basal levels of testosterone were higher both in plasma and in testes of acutely intoxicated animals, the circulating levels of luteinizing hormone (LH) were not affected in either group, nor was the LH‐releasing hormone content of the median eminence. The density of [125I]LH/human chorionic gonadotrophin (hCG) binding sites in testicular homogenates was reduced by saturnism in both groups, concomitant with a significantly increased apparent affinity constant of the hormone‐receptor complex. These data can be viewed as the result of a mixture of specific lead toxicity (e.g. at the enzyme level) with other more general actions (e.g. at the level of the hypothalamus‐pituitary‐testicular axis).
Pathological mechanisms of hepatic tumour formation in rats exposed chronically to dietary hexachlorobenzene
Authors: Carthew P. , Smith A. G. 
Published: October 2006

AbstractThe chronic dietary administration of hexachlorobenzene (HCB) to rats for a year or more results in the formation of liver tumours described as hepatocellular carcinomas, hepatomas or haemangiomas. The hepatotoxicity of HCB, which is greatest in hamsters and rats, gives rise to peliosis and necrosis with haemosiderosis. This pattern of hepatotoxicity indicates vascular damage, which through haemosiderosis could increase not only the toxic effect of HCB to hepatocytes but also its tumourogenic potential. The present study confirmed vascular damage by the identification of widespread fibrin deposits in the livers of rats chronically exposed to HCB, using an antibody to rat fibrin. Based on our study we suggest that the formation of hepatomas and haemangiomas with elements of peliosis (cystic blood‐filled cavities) could be explained by the compensatory hyperplastic responses to hepatocellular necrosis and by the simultaneous loss of hepatocellular cords. The accumulation of iron in the liver would strongly potentiate the development of hepatic tumours, as has been found in HCB and polychlorinated biphenyl‐treated mice with iron overload. The implications of this non‐genotoxic mechanism of hepatoma formation for the assessment of human health risk are discussed.
Analysis of feed blends containing microencapsulated 2‐ethyl‐1‐hexanol: Verification of homogeneity and stability
Authors: Arneson Dora W. , Kuhn Gustav O. , Jameson C. W. 
Published: October 2006

Abstract2‐ethyl‐1‐hexanol (2‐EH) was nominated for carcinogenicity testing by the National Toxicology Program because it is a high‐volume chemical and a major metabolite of di(2‐ethylhexyl)phthalate, a known hepatocarcinogen and a known contaminant in blood storage bags. In addition to uses as an intermediate in the manufacture of plasticizers, 2‐EH is also used as a solvent, a lubricant and as a finishing compound for paper and textiles. The preferred route of administration for the carcinogenicity studies was oral via the diet. However, feed blends containing neat 2‐EH were not sufficiently stable for feed studies. Dosed feed blends prepared with neat 2EH retained only 86% of the theoretical concentration after blending, and 46% of theoretical after storage for 2 days in a rat cage environment. Feed blends containing microencapsulated 2‐EH were sufficiently stable for toxicity studies: no losses of 2‐EH were observed after blending, feed blends stored for 7 days in a rat cage retained 99% of the theoretical concentration and blends stored in sealed containers at room temperature for 21 days retained 97% of the theoretical concentration. These studies demonstrate the potential for microencapsulation technology to eliminate dose formulation problems associated with volatile chemicals.
Preclinical safety studies with recombinant human interleukin 6 (rhil‐6) in the primate callithrix jacchus (marmoset): Comparison with studies in rats
Authors: Ryffel B. , Weber M. 
Published: October 2006

AbstractThe haemopoietic and immunostimulatory properties of recombinant human interleukin 6 (rhIL‐6) might be used clinically in cancer patients. For the preclinical assessment of the safety of such a therapy, we chose the primate marmoset (Callithrix jacchus) and Wistar rats.Recombinant hIL‐6 given to marmosets at doses of up to 1000 μg kg−1 day−1 over 4 and 9 weeks did not induce fever and was very well tolerated. Haematological alterations included a sustained two‐ to threefold increase of thrombocyte counts, peaking at 4 weeks, as well as an increase in neutrophils and basophils. The number of bone marrow megakaryocytes at 4 and 9 weeks was not increased, but the ploidy grade was augmented. An acute‐phase protein response was observed within 24 h after the first IL‐6 administration, which reached a maximum after 1 week. The acute‐phase protein response was not accompanied by functional or morphological signs of hepatocellular damage. Increased immunoglobulin and soluble IL‐2 receptor in the serum levels reflected systemic immunostimulation.Recombinant hIL‐6 was also given to rats at 500 μg kg−1 day−1 s.c. for 4 weeks, where it induced a stimulation of thrombopoiesis associated with increased platelet counts within 1 week. Furthermore, rhIL‐6‐treated rats had signs of immunostimulation and increased acute‐phase reactants in serum, as in marmosets. There was no evidence of renal glomerular or hepatic pathology.In conclusion, despite the pleiotrophic effects of IL‐6 observed in vitro, prolonged administration of rhIL‐6 induced quite a selective stimulation of thrombopoiesis and the immune system, which were not associated with any major adverse effect in the two animal species. Since neutralizing antibodies developed against rhIL‐6 in both species within 2–4 weeks, which abolished the biological effect of IL‐6, the conductance of long‐term studies with rhIL‐6—especially on possible tumour‐promoting effects—are not warranted.
Effects of ricin on the ability of rabbit arteries to contract and relax
Authors: Christiansen Victoria J. , Hsu Chia‐Hsuh , Zhang Lin , Robinson Casey P. 
Published: October 2006

AbstractRicin, a toxic lectin from castor beans, reduces blood pressure. The current studies determined the effect of ricin on contractions in response to norepinephrine (NE) of rabbit central ear artery, endothelium‐dependent relaxations to methacholine and ATP of aorta rings and endothelium‐independent relaxations to papaverine in central ear artery and aorta rings. Rabbits were given 0.11 or 0.22 μg kg−1 ricin i.v. and 18 h, 4 days, or 7 days later the arteries were removed and tested. Maximal contractions to NE were increased by 8–23% (P > 0.05) with ricin treatment. The EC50 was increased in five of six ricin‐treated groups, although only significantly so at 18 h after a minimum lethal dose of ricin. Maximum relaxations to methacholine were increased by 20–57% (P > 0.05) at 18 h following both ricin doses but returned to control values at later time points. Relaxations in response to ATP were significantly enhanced in all ricin‐treated groups (95–205%) except in the 18 h and 4‐day 0.11 μg kg−1 dose groups where the increase was 0–46%. Relaxations in response to papaverine were not altered in either artery. Thus, ricin decreases the sensitivity of the rabbit central ear artery to NE and increases endothelial‐dependent relaxations of the rabbit aorta. Therefore, decreased blood pressure following ricin administration may be due to vasodilation caused by decreased vascular contractions and increased endothelial‐dependent vascular relaxation.
Protective effect of colchicine on acute liver damage induced by CCL4. Role of cytochrome p‐450
Authors: Martínez Martín , Mourelle Marisabel , Muriel Pablo 
Published: October 2006

AbstractThe aim of this work was to study if colchicine protects against CCl4 ‐induced changes in hepatic biochemical parameters by reducing cytochrome P‐450, by comparing the effects of colchicine and SKF 525‐A, a well‐known inhibitor of cytochrome P‐450. Our results show that both drugs reduced the cytochrome P‐450 content and p‐nitroanisole o‐demethylase activity to the same extent. However, colchicine afforded a total protection from markers of liver injury, while SKF 525‐A protected only partially. The difference in the hepatoprotective activity of both drugs indicates that the beneficial effect of colchicine cannot be attributed solely to the inhibition of the activation of CCl4. Other actions, perhaps at the level of the propagation of lipid peroxidation or a ‘membrane‐stabilizing’ effect cannot be ruled out.
Epidermal carcinogenesis studies of eds liquids
Authors: McKee R. H. , Plutnick R. T. 
Published: October 2006

AbstractA series of liquids representing different potential design options or operating configurations for the EDS direct coal liquefaction process* were evaluated for skin cancer potential. All of the samples that contained substantial amounts of material boiling above 370°C were active dermal carcinogens; tumor yields were near 100% and median times to tumor development generally ranged from 30 to 40 weeks. Two liquids that boiled below ca. 200°C were tested and each produced one squamous cell tumor. These data suggested that high‐boiling‐point, coal‐derived liquids are likely to be relatively potent dermal carcinogens; whereas low‐boiling‐point liquids do not possess significant carcinogenic potential. Based on a comparison of the carcinogenic potency data, liquids produced by the EDS process apparently do not present a significantly greater dermal carcinogenic hazard than other coal‐derived materials of similar boiling range.
Mechanism of citrinin‐induced dysfunction of mitochondria iii. Effects on renal cortical and liver mitochondrial swelling
Authors: Chagas Generoso M. , Oliveira Ma. Benigna M. , Campello Annibal P. , Klüppel Ma. Lúcia W. 
Published: October 2006

AbstractThe effects of the mycotoxin citrinin on renal cortical and liver mitochondrial swelling were studied. Citrinin decreases the rate of swelling induced by the valinomycin–K+ complex, suggesting that the mycotoxin interferes with the mitochondrial membrane fluidity. Citrinin promotes reduction of the amplitude of swelling in the presence of Na+ ions. This alteration reflects interference with complex I of the respiratory chain and ATP synthase complex activity without disarranging the inner mitochondrial membrane, in view of the fact that the shrinkage was not affected. The effect increases with citrinin concentration. Renal tissue is more susceptible than hepatic tissue.