bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial effect of acetylcysteine on cisplatin nephrotoxicity in rats
Authors: Appenroth Dorothea , Winnefeld Klaus , Schröter Heinz , Rost Michael 
Published: October 2006

AbstractThe influence of acetylcysteine (ac‐cys) on cisplatin (CP) nephrotoxicity was investigated in female Wistar rats. Administration of 0.6 mg CP 100 g−1 body wt. was followed by oliguria and proteinuria, as well as a significant increase of blood urea nitrogen concentration. The i.p. administration of 0.6 mg CP 100 g−1 body wt. concomitantly with 100 mg ac‐cys 100 g−1 body wt. s.c. completely abolished the nephrotoxic effects of CP. However, following this, the Pt concentration in kidney was decreased significantly by ac‐cys treatment. This was caused by the enhanced urinary excretion of Pt. The same effect on CP nephrotoxicity appeared when CP and ac‐cys were dissolved together in solution prior to injection. It could be shown that in this solution a ligand exchange reaction of CP by ac‐cys started immediately, resulting in increased renal excretion and decreased Pt concentration in kidney.From our results we concluded that the protective effect of ac‐cys on CP nephrotoxicity is based on the formation of a complex unsuitable for tubular reabsorption.
The toxicology of chromium with respect to its chemical speciation: A review
Authors: Katz Sidney A. , Salem Harry 
Published: October 2006

AbstractThe properties of trivalent and hexavalent chromium are reviewed with respect to acute and chronic oral toxicity, dermal toxicity, systemic toxicity, toxicokinetics, cytotoxicity, genotoxicity and carcinogenicity. The hexavalent chromium compounds appear to be 10–100 times more toxic than the trivalent chromium compounds when both are administered by the oral route. Dermal irritancy and allergy are more frequently caused by contact with soluble hexavalent chromium compounds. The cytotoxicity of soluble and insoluble hexavalent chromium compounds to fibroblasts is 100‐1000 times greater than that demonstrated by trivalent chromium compounds. In short‐term tests, the hexavalent chromium compounds demonstrated genotoxic effects four times more frequently than did the trivalent chromium compounds. Carcinogenicity appears to be associated with the inhalation of the less soluble/insoluble hexavalent chromium compounds. The toxicology of chromium does not reside with the elemental form. It varies greatly among a wide variety of very different chromium compounds. Oxidation state and solubility are particularly important factors in considering the toxicity of chromium with respect to its chemical speciation.
Mutagenic potential of nitroguanidine and nitrosoguanidine in the Drosophila melanogaster sex‐linked recessive lethal assay
Authors: Gupta Raj K. , Korte Don W. , Reddy Gunda 
Published: October 2006

AbstractNitroguanidine (NG) and its degradation product nitrosoguanidine (NSG) were evaluated for their mutagenic potential by using Drosophila melanogaster sex‐linked recessive lethal (SLRL) assay. Following 72 h of feeding exposure, NG and NSG at concentrations of 4–8 μg ml−1 and 15–20 mg ml−1, respectively, were not mutagenic in the test system. The frequencies of mutations for NG and the negative control were 0.188% and 0.096%, respectively. The frequencies of mutations for NSG and the negative control experiments were 0.049% and 0.05%, respectively. The positive control mutation frequencies were 15% and 17.8% for the two assays. The differences between the mutation frequencies of NG and NSG and their negative controls were not significant.
Whole‐body autoradiographic disposition, elimination and placental transport of [14C]Tri‐o‐cresyl phosphate in mice
Authors: Ahmed Ahmed E. , Jacob Sam , Soliman Salah , Ahmed Nabila , Osman Khalid , Loh Jiann‐Ping , Romero Natasha 
Published: October 2006

AbstractTri‐o‐cresyl phosphate (TOCP) is used commercially as a plasticizer and flame retardant. The disposition, metabolism, elimination and transplacental uptake of [phenyl‐U‐14C]TOCP and/or its metabolites, in pregnant and non‐pregnant mice, were examined. Pregnant (18th‐day gestation) and non‐pregnant, ICR mice were given an i.v. dose of [14C]TOCP (557 μCi kg−1; Specified activity 4.83 μCi μmol−1). At various time intervals (1, 24, 48 and 72 h) the animals were processed for whole‐body autoradiography (WBA). Over 72 h the nonpregnant mice excreted 55% of the 14C in the urine and 9% in the feces, while excretion in the urine and feces by the pregnant mice was 50% and 9% of the total dose, respectively. The WBA and its computerassisted image analysis indicated extensive distribution of the 14C label originally dosed as [14C]TOCP in pregnant mice and their fetuses. The retention of radioactivity in organs such as lung, spleen, gall‐bladder and liver of mother and its fetuses suggest that these are the target sites of TOCP toxicity. The distribution in non‐pregnant and pregnant mice and in the fetal tissues followed a similar pattern in uptake and retention until 72 h. Brain and spinal cord had the least amount of [14C]TOCP. This finding may support reports that explain the insensitivity of the mice towards organophosphate‐induced delayed neurotoxicity (OPIDN) of TOCP.
The diacetylmonoxime assay of urea, its application to the assay of diacetylmonoxime and a comparison with other methods for the analysis of diacetylmonoxime
Authors: Dawson Raymond M. 
Published: October 2006

AbstractThe experiments reported herein were designed to identify the best assay of diacetylmonoxime (DAM) in biological fluids, with particular emphasis on detection limits. Initially, four variations of the assay of urea with excess DAM were compared. The best method, published in 1977, was one that includes thiosemicarbazide, 4‐aminoantipyrine and ceric ammonium sulphate in the acid reagent; it is fast, gives a reasonably stable chromophore and displays good linearity. However, the reaction was two or more times less sensitive when applied to the assay of DAM, with urea in excess, by interchanging the amounts of urea and DAM. Further, the calibration graphs did not pass through the origin, and one of the methods gave a mixture of two chromophores. None approached the sensitivity of a DAM‐urea reaction specifically designed to assay biacetyl (formed from DAM by acid hydrolysis) and published in 1968. This method, using antipyrine and arsenicosulphuric acid, is also fast, with good linearity and a stable chromophore, but is sensitive to interference by plasma and urine. An alternative photometric assay that does not involve urea was equally sensitive. It had the advantage of less interference by plasma and urine but was more time‐consuming. Both of these photometric methods had a limit of detection of ca. 0.2 μg DAM, similar to that of a high‐performance liquid chromatography (HPLC) assay. Sample clean‐up is necessary before application of the HPLC assay.
Evaluation of the genotoxic potential of zinc pyrithione in the Salmonella mutagenicity (Ames) assay, CHO/HGPRT gene mutation assay and mouse micronucleus assay
Authors: Skoulis N. P. , Barbee S. J. , Jacobson‐Kram D. , Putman D. L. , San R. H. C. 
Published: October 2006

AbstractThe mutagenic potential of zinc pyrithione (Znpt) was evaluated in vitro in the Salmonella/mammalian microsome plate incorporation mutagenicity (Ames) assay and the CHO/HGPRT gene mutation assay. The clastogenic potential of Znpt was evaluated in vivo using the mouse micronucleus test. Znpt was negative in the Ames test in five tester strains in the presence and absence of rat liver microsomal enzymes when assayed at concentrations ranging between 10 and 333 μg per plate and between 0.03 and 33 μg per plate, respectively. Znpt also produced negative results in the CHO/HGPRT assay. No significant increases in mutant frequencies were seen in the presence and absence of rat liver microsomal enzymes. In each case, the highest concentrations reduced cellular viability by 83% and 85%, respectively. Znpt also did not induce increased frequencies of micronuclei in mouse bone marrow cells when tested at the maximally tolerated dose (MTD) (44 mg kg−1). These data support the conclusion that Znpt lacks genotoxic activity under the conditions of these tests.
A proposed screen for evaluating low‐molecular‐weight chemicals as potential respiratory allergens
Authors: Gauggel Dorothy L. , Sarlo Katherine , Asquith Thomas N. 
Published: October 2006

AbstractAllergic asthma can result when reactive low‐molecular‐weight chemicals (LMWCs) haptenate carrier proteins to form immunogenic conjugates, which then induce specific allergic antibodies. As part of an overall assessment process for evaluating the allergenic potential of LMWCs, an in vitro test for detecting the covalent derivatization of proteins by LMWCs was developed. In the assay, globulin‐free serum albumins were incubated with increasing concentrations of a given LMWC and the mixtures separated via reversed‐phase high‐performance liquid chromatography (HPLC). Derivatization was monitored by shifts in the retention time of native versus modified protein. Retention time shifts were seen for most haptens when incubated with human serum albumin at a 50:1 (hapten:protein) starting molar ratio. Some haptens changed the retention time of the protein at a 5:1 initial ratio. Almost all chemicals that non‐covalently bind to proteins did not change the protein retention time, even when incubated at 1500:1 molar ratios. The screen correctly identified 12/14 known human allergenic haptens and 23/24 non‐allergenic LMWCs. It cannot detect sensitizers which must be metabolized into reactive haptens. This screen can be incorporated into an overall risk assessment approach for evaluating chemicals as respiratory allergens.
An attempt to improve the SOS chromotest responses
Authors: Hoflack J. C. , Férard J. F. , Vasseur P. , Blaise C. 
Published: October 2006

AbstractThe SOS Chromotest was carried out on leachates of ten industrial wastes with the standard procedure and a miniaturized version with microplates. The two methods gave identical results in nine samples (eight negative and one positive). A simple additional manipulation is described for the identification of the false positive response that is frequently observed with complex mixtures. It involves challenging the SOS Chromotest bacteria with samples (having previously shown a positive genotoxic response) just before the enzymatic activities (i.e. β‐galactosidase and alkaline phosphatase) are estimated colorimetrically. This additional step eliminates discrepancies between the results for the standard and the miniaturized procedures.
Induction of chromosomal aberrations and sister chromatid exchange in vivo and in vitro by the insecticide cypermethrin
Authors: Amer Soheir M. , Ibrahim Aziza Abd‐El Samie , El‐Sherbeny Kawser M. 
Published: October 2006

AbstractThe induction of chromosomal aberrations and sister chromatid exchange in vivo in mouse spleen and bone marrow as well as in vitro in cultured mouse spleen cells by the insecticide ‘Cypermethrin’ (cistrans 1:1) was investigated.The percentage of chromsomal aberrations in the spleen and in the bone marrow as almost the same and reached its maximum 6 h following i.p. injection. The aberrations induced were chromatid and chromosome gaps, fragments and tetraploidy. The insecticide caused a significant and dose‐dependent increase in the frequency of sister chromatid exchanges (SCEs) in mouse bone‐marrow cells: it reached 11.12 ± 0.05 per cell after treatment with Cypermethrin at 300 mg kg−1 body wt. compared with 3.7 ± 0.14 per cell and 4.4 ± 0.26 per cell in the solvent and control, respectively.The percentage of viable cells in mouse spleen cell cultures reached 87.4% and 99.9% relative to the control after treatment of the cell cultures with 10−3 and 10−7 Cypermethrin, respectively. All the tested concentrations of Cypermethrin (0.25–400 μg ml−1) induced a high percentage of metaphases with chromosomal aberrations after 4 h of treatment. The mean frequency of SCEs per cell reached 15.1 ± 0.05 after treatment with Cypermethrin at 4.00 μg ml−1 compared with 8.6 ± 0.23 and 5.9 ± 0.39 in the solvent and control, respectively.The results indicate that Cypermethrin is genotoxic in mouse spleen and bone marrow as well as in cultured mouse spleen cells.
Effects of high exposure concentrations of inhaled low‐toxicity dust on pulmonary function in guinea pigs
Authors: Wolff R. K. , Collins M. J. , Carlson K. H. , Allen D. L. , Dorato M. A. 
Published: October 2006

AbstractThe acute pulmonary function response to graded levels of a low toxicity dust was studied in guinea pigs. Four groups of five male guinea pigs each were exposed to mean concentrations of 0, 0.25, 1.01 and 5.39 mg Foundry Hill Clay I−1 air with mass median aerodynamic diameters of 2.6, 4.6 and 6.7 μm, respectively. There was a 15‐min pre‐exposure period to clean air, a 1‐h exposure to the test atmosphere and then a 1‐h recovery period with exposure to clean air. Concentration‐related changes, compared to the pre‐exposure period, occurred with a rapid onset in a number of parameters. Generally, the severity of observed effects increased with exposure time and, therefore, with inhaled dose. Statistically significant changes (P<0.05) were observed in tidal volume, dynamic compliance, dynamic resistance, flow, pressure and minute volume during the last 15 min of exposure. The observed changes were consistent with acute bronchoconstriction. These effects reversed rapidly and there were no significant changes 1 h post‐exposure. These results suggest that adverse physiological responses of short duration can occur when animals are exposed via inhalation to low‐toxicity materials in the concentration range 0.25‐5 mg I−1.
High‐performance liquid chromatography detection of sulfide in tissues from sulfide‐treated mice
Authors: Mitchell Thomas W. , Savage Joseph C. , Gould Daniel H. 
Published: October 2006

AbstractThe biological and forensic use of ion‐interaction reversed‐phase high‐performance liquid chromatography for the determination of hydrogen sulfide‐derived methylene blue is evaluated by measuring the sulfide content in tissues from sulfide‐treated mice. Various preparative conditions were examined. The determinations of background levels of sulfide from brain, liver and kidney were compared to sulfide levels from mice exposed to 60 μg g−1sodium hydrosulfide. At the time of death, significant increases above background sulfide levels were measured for all three biological tissues. To evaluate its forensic potential, we used this sulfide detection methodology to evaluate comparatively the sulfide levels from fresh and frozen samples of brain, liver and kidney. The stability of sulfide levels obtained from frozen brain makes this tissue the most reliable tissue for forensic evaluation. Samples of brain, liver and kidney obtained within 24 h of death by sulfide intoxication had demonstrable elevations in sulfide concentration.
Urinary thiodiglycolic acid and thioether excretion in male rats dosed with 1,2‐dichloroethane
Authors: Payan J. P. , Beydon D. , Fabry J. P. , Brondeau M. T. , Ban M. , de Ceaurriz J. 
Published: October 2006

Abstract1,2‐dichloroethane (DCE) is extensively metabolized and partially excreted in urine as thioether compounds, which include thiodiglycolic acid (TDGA). In this study, we have compared the urinary excretion of TDGA and thioethers in the rat after administration of increasing doses of DCE. Male Sprague Dawley rats were given a single oral dose of labelled [14C]DCE (0.125 to 8.08 mmol kg−1 body wt.) and 24‐h urine samples were collected. The TDGA and thioethers were determined in urine by a gas chromatography method and by the thioether assay after alkaline hydrolysis, respectively. The percentage of the administered radioactivity that was excreted in urine decreased with increasing dose of DCE and ranged between 63 and 7.4%. The amount of TDGA increased proportionally to the DCE dose up to 1.01 mmol DCE kg−1 body wt. and corresponded to 0.22 mmol TDGA mmol−1 DCE. Up to 0.25 mmol DCE kg−1 body wt., the amount of thioethers recovered in urine was not significantly different as compared to the vehicle control group (11.8 ± 0.6 μmol SH equiv. kg−1 body wt., n = 10). From the 0.25–4.04 mmol DCE kg−1 body wt. dose, the amount of thioethers increased linearly with the dose of DCE and corresponded to 0.028 mmol SH equiv. mmol−1 DCE. The ratio between urinary thioethers and TDGA increased with the DCE dose and reached 0.17 ± 0.01 (n = 5) at a dose of 8.08 mmol DCE kg−1 body wt. Moreover, TDGA contents determined in urine by gas chromatography before and after alkaline hydrolysis were not significantly different.These results have shown that urinary TDGA was a much better monitor of DCE exposure than total thioethers, not only in specificity but also in sensitivity. Moreover, they point out that TDGA was not hydrolysed under alkaline conditions, making the thioether assay inappropriate for determining TDGA content.
Predicted toxicities of aryl alkanols and related compounds
Authors: Schultz T. Wayne , Lin David T. , Culberson Ronnie W. 
Published: October 2006

AbstractThe relative toxicity of selected aryl and/or alkyl alcohols was evaluated in the batch culture Tetrahymena pyriformis population‐growth impairment assay. Chemicals evaluated included normal and branched primary alcohols with mono‐, bi‐ or diaromatic substituents as well as aryl‐substituted ethers. Log 1‐octanol/water partition coefficients (log Kow) along with previously developed quantitative structure‐activity relationships (QSARs) for both the non‐polar narcosis and polar narcosis mechanism of action were used to predict relative toxicity. Observed and predicted toxicities measured as log IGC50−1 were compared. All phenols and naphthylsubstituted compounds, as well as the biphenyl methanols, benzhydrols and 1,1‐diphenylethanol, model more accurately as polar narcotics. Both monoaromatic‐ and diaromatic‐substituted branched arylalkyl alcohols, as well as monoaromatic ethers, model best as non‐polar narcotics. The C1‐C6 straight‐chain aryl alkanols, as well as 3‐phenyl‐1‐butanol, model intermediately between non‐polar and polar narcosis. The triaromaticsubstituted alcohol was not toxic at saturation. These findings are consistent with the idea that narcosis, the reversible state of arrested bioactivity, is a series of mechanisms.
Testicular lesions by chronic administration of cocaine in rats
Authors: Barroso‐Moguel Rosario , Méndez‐Armenta Marisela , Villeda‐Hernández Juana 
Published: October 2006

AbstractAlthough cocaine is a common drug of abuse, its effects on the testicular structure have not been studied in depth. We report here the testicular lesions produced by chronic cocaine administration to rats. Twentyeight male Wistar rats weighing 225–250 g were used throughout. Fourteen of them (controls) were injected i.p. with saline solution and the remaining 14 received 30 mg kg−1 day−1 i.p. of aqueous cocaine hydrochloride solution. Animals from both groups were sacrificed at variable times: 7, 15, 30, 45, 60, 75 and 90 days of treatment. Histopathological examination of the testes showed initial alterations at day 15: capillary dilatation; interstitial oedema with lipoid drops due to incipient necrosis of interstitial cells; and necrosis of the cells of the seminiferous tubules. Lesions progressed until 90 days of treatment, showing atrophic and necrotic cells and terminal tubule fibrosis. At this time, the testes were found to be diminished in size. The seminiferous tubules were shrunken, of small diameter and contained necrotic spermatogenic cells and fibrosis. These lesions may produce testosterone diminution and thus sterility due to the disappearance of spermatogenesis.
Metabolite pharmacokinetics of soman, sarin and GF in rats and biological monitoring of exposure to toxic organophosphorus agents
Authors: Shih Ming L. , McMonagle Joseph D. , Dolzine Theodore W. , Gresham Vincent C. 
Published: October 2006

AbstractThis study reports on the pharmacokinetics of the elimination of the metabolites of three toxic organophosphorus compounds (soman, sarin and GF). Urine, blood and lung tissue were collected from rats dosed subcutaneously at 75 μg kg−1. Urinary excretion of the metabolite was the major elimination route for these three compounds. The major differences among them were primarily the extent and rate of excretion. The hydrolyzed form, alkylmethylphosphonic acid, was the single major metabolite formed and excreted in urine by a non‐saturable mechanism. Nearly total recoveries of the given doses for sarin and GF in metabolite form were obtained from the urine. The terminal elimination half‐lives in urine were 3.7x ± 0.1 and 9.9 ± 0.8 h for sarin and GF, respectively. Soman metabolite showed a biphasic elimination curve with terminal half‐lives of 18.5 ± 2.7 and 3.6 ± 2.2 h. Soman was excreted at a slower rate with a recovery of only 62%. Lung was the major organ of accumulation for soman. In blood the toxic agents were concentrated more in red blood cells than in plasma. The acid metabolites can serve as a better chemical marker for monitoring organophosphorus exposure in humans via their higher concentration and longer half‐life in urine than the parent compounds.
Role of extracellular glutathione and γ‐Glutamyltranspeptidase in the disposition and kidney toxicity of inorganic mercury in rats
Authors: De Ceaurriz J. , Payan J. P. , Morel G. , Brondeau M. T. 
Published: October 2006

AbstractThe role of extracellular glutathione (GSH) and membrane‐bound γ‐glutamyltranspeptidase (γ‐GT) as contributory factors in the disposition and toxicity of inorganic mercury (HgCl2, 1 mg kg−1, i.p.) was investigated in rats pretreated with acivicin (AT‐125, 10 mg kg−1), a γ‐GT inhibitor.A high degree of γ‐GT inhibition (75%) and of protection (90%) against HgCl2‐induced nephrotoxicity was obtained in γ‐GT‐inhibited rats 24 h post‐treatment. Pretreatment with acivicin affected the fractional distribution profile of 203Hg, resulting in a twofold decrease in the renal incorporation of mercury 4 h posttreatment and a threefold increase in the 24‐h urinary excretion of mercury. Plasma radioactivity remained constant over 24 h in rats dosed with 203Hg alone, whereas it decreased by 60% between 4 h and 24 h in γ‐GT‐inhibited rats. In γ‐GT‐inhibited rats treated with HgCl2 the renal and plasma reduced glutathione (GSH) content increased by 68% and 330% respectively, as compared to controls. The γ‐GT inhibition affected the distribution profile of mercury within urinary proteins, shifting the binding of mercury from the inghmolecular‐weight fraction (3% against 80%) to the low‐molecular‐weight fraction (72% against 10%). A significant but less impressive shift of mercury from the ingh‐ to the low‐molecular‐weight fraction also arose in the plasma.These results taken together support the pivotal role of extracellular GSH and membrane‐bound γ‐GT in the renal incorporation, toxicity and excretion of inorganic mercury in rats.
Mechanism of antifoaming action of simethicone
Authors: Brečević Ljerka , Bošan‐Kilibarda Ingrid , Strajnar Franjo 
Published: October 2006

AbstractThe mechanism of the foam‐inhibiting action of simethicone, mainly used against flatulence, has been studied. Its effect on foaming systems containing synthetic gastric juice and a surface‐active substance (anionic surfactant, cationic surfactant, soap solution) was quantitated by measuring the surface tension, foam stability and initial foam density. The effect of simethicone on each of the examined systems was the result of the combination of two actions: the drainage of liquid from foam films and the rupture of relatively thick liquid films. The mechanism of these actions may be described as the liquid drainage followed by bridging of the liquid film by polydimethylsiloxane droplets, helped by hydrophobic silica particles also present in the antifoaming agent, leading to the rupture of the film surface and air escape.