bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of rat β2‐microglobulin in urine and in serum. II. Application of its urinary measurement to selected nephrotoxicity models
Authors: Viau C. , Bernard A. , Ouled A. , Lauwerys R. 
Published: October 2006

Abstractβ2‐microglobulin (β2‐m) was measured in the urine of rats by a specific immunoassay based on latex particles agglutination. the excretion of this protein was compared to the excretion of the enzyme β‐N‐acetyl‐D‐glucosaminidase (NAG), albumin and amino acids in rats treated with either a single dose of sodium chromate (5 and 10 mg kg−1), repeated doses of gentamicin (5 and 20 mg kg−1), or cadmium (1 mg kg−1), and in aging rats (from 2 to 20 months). All treatments resulted in an early increased excretion of β2‐m indicative of functional alterations of the proximal tubular cells. An increased NAG excretion was observed only at the highest dose of chromate and in the cadmium model but the relative increases of β2‐m were much larger (up to 200 times the control values against four times the control values for NAG). From 2 to 20 months of age, urinary β2‐m increases by a factor of four. Aminoacids excretion showed little sensitivity in the various models. Albumin showed little variations in purely tubular or in the tubular phase of renal injury but the chronic progressive nephrosis of aging rats caused a 40‐fold increase in its excretion between 2 and 20 months of age. Therefore urinary β2‐m, albumin and albumin/β2‐m ratio provide useful tools in the assessment of nephrotoxicity and of its mechanisms in various experimental models.
Mutagenicity testing of selected analgesics in Ames Salmonella strains
Authors: Oldham James W. , Preston Robert F. , Paulson John D. 
Published: October 2006

AbstractAcetaminophen (APAP), aspirin (ASA), phenacetin (PA) and ibuprofen (IB) were tested for mutagenic activity in the Ames Salmonella plate incorporation assay using strains TA98, TA100, TA1535, TA1537 and TA1538. These analgesics were tested in four separate tests: without metabolic activation, and in the presence of a rat, hamster or mouse liver post‐mitochondrial supernatant (S‐9, Aroclor 1254‐induced). Treatment of all five strains of Salmonella with APAP, ASA or IB under all four metabolic conditions did not induce any appreciable increases in revertant colony counts, as compared to the negative controls. A dose‐related increase in revertant colony counts, reaching levels twice the negative control values, were seen with PA at doses ⩾500 μg per plate. This response was only seen in strain TA100 in the presence of hamster S‐9. Therefore, these findings constitute a positive result for PA in the Ames test. APAP, ASA and IB did not show any mutagenic potential under these conditions of testing. These findings are discussed along with previously published results concerning the genotoxicity of these analgesics.
The toxicity of brass dust to the microalgaeAnkistrodesmus falcatusandSelenastrum capricornutum
Authors: Haley Mark V. , Johnson Dennis W. , Hart Gayle S. , Muse William T. , Landis Wayne G. 
Published: October 2006

AbstractThe toxicity of brass dust was examined by conduction 96 h growth inhibition tests. Two species of algae were used,Ankistrodesmus falcatus(EC50=0.316 mg brass/I) andSelenastrum capricrnutum(EC50=0.056 mg brass/I). Brass dissociate into two components, Cu (68.5%) and Zn (27.5%). Enhanced algal growth was exhibited at concentrations of 0.01 and 0.001 mg brass/I. Available literature on the toxicity of copper toS. capricornutum(EC50=0.047 mg Cu/I), indicate that the toxicity of brass dust is due to the ionized copper. Reported toxicities of zinc are orders of magnitude lower than copper. The ionization of the brass is dependent on pH and hardness. The literature cites cases in which copper toxicity varies with pH, clay content and dissolved organics. At present little is known of the fate and distribution of brass dust upon the release into the environment. However, the presence of heavy metals has consistently been shown to impact aquatic systems.
Combined effect of ethanol and carbon disulphide on cytochrome P‐450 monooxygenase, lipid peroxidation and ultrastructure of the liver in chronically exposed rats
Authors: Wrońska‐Nofer Teresa , Klimczak Jadwiga , Wiśniewska‐Knypl Justyna M. , Jajte Jolanta , Opalska Barbara 
Published: October 2006

AbstractA 5‐month treatment of rats with ethanol (10% solution in drinking water) stimulated aniline p‐hydroxylase and the microsomal ethanol oxidizing system (MEOS) by 140 and 70%, respectively, cytochrome P‐450 by 22% and accompanied by lipid peroxidation by 40% in microsomes. It also caused smooth endoplasmic reticulum (SER) proliferation and rough endoplasmic reticulum (RER) degranulation in hepatocytes. Repeated inhalatory exposure of rats to 1.5 g/m3 of CS2, 5h daily, 5 days a week for 5 months decreased aniline p‐hydroxylase and MEOS by 70 and 55% respectively, doubled hexobarbital sleeping time and depressed cytochrome P‐450 by 30% and its conversion to cytochrome P‐420; these effects were accompanied by the appearance of cytochrome P‐420, the intensification of lipid peroxidation in microsomes and some degranulation of RER in hepatocytes. Combined exposure of rats to ethanol and CS2 resulted in a significant potentiation of the inhibitory effects of CS2 on cytochrome P‐450 mono‐oxygenase and MEOS but with enhancement of CS2 effects on the liver microsomal mono‐oxygenase, but CS2 decreased the effect of ethanol on SER proliferation. The interaction both on the biochemical and the morphological level can be explained with the ethanol‐stimulated biotransformation of CS2 to reactive electrophilic derivative(s), the subsequent destruction of cytochrome P‐450 to cytochrome P‐420 and the intensification of lipid peroxidation.
Influnce of manganese on the gastrointestinal absorption of cadmium in rats
Authors: Sarhan Mohammad J. , Roels Harry , Lauwerys Robert , Reyners Hubert , De Reyners Elva Gianfelici 
Published: October 2006

AbstractFour groups of male rats were given the following oral treatment: control group (n = 20) deionized drinking water, Mn group (n = 20) deionized drinking water containing 56 ppm Mn2+ (1 mmol/l), Cd group (n = 10) deionized drinking water containing 112 ppm Cd2+ (1 mmol/l) and Cd+Mn group (n = 10) deinonized drinking water containing 112 ppm Cd2+ and 56 ppm Mn2+. Half of each group was sacrificed after 4 weeks and the other half after 8 weeks of treatment. At each time interval, the mean levels of Mn in blood, in urine and in the various tissus did not differ between the control and Mn groups. Furthermore, comparable Mn levels were found after 4 and 8 weeks of treatment. Microscopical examination of the brain failed to reveal any overt morphological alteration in the Mn group. With respect to the control group, the Cd and Cd + Mn groups exhibited increased levels of Cd in blood, urine, liver, whole kidney, kidney cortex and in brain (cortex, cerebellum, basal ganglia), but the Cd + Mn groups showed invariably lower levels than the Cd group after 4 weeks as well as after 8 weeks. These results suggest that the rate of gastrointestinal absorption of Cd is decreased by supplementation of the drinking water with a ‘non‐toxic’ dose of Mn2+.
Urinary tract effects of phensuximide in the Sprage‐Dawley and Fischer 344 rat
Authors: Rankin Gary O. , Cressey‐Veneziano Kim , Wang Ruu‐Tong , Brown Patrick I. 
Published: October 2006

AbstractPhensuximide is a succinimide antiepileptic drug useful in the treatment of petit mal epilepsy. Phensuximide has been reported to be nephrotoxic in man but not in animals. In the present study, the effects of single and subacute administration for seven days of phensuximide on renal function and urinary tract morphology were evaluated in Sprague‐Dawley and Fischer 344 rats. Single administration of phensuximide (1.25 mmol/kg, ip) induced mild changes in renal function (trace hematuria, increased proteinuria and decreased p‐aminophippurate uptake). No morphological changes were observed at 24 hr. Subacute administration of phensuximide (0.6 mmol/kg/day, ip) produced diuresis in the Sprague‐Dawley rats, but little functional evidence of nephrotoxicity. Renal morphological changes in Sprague‐Dawley rats were seen primarily in distal segments of the nephrons. These changes were characterized by distensions of the basal infoldings, apical protrusions, and occlusion of some lumen. In the Fischer 344 rat, subacute phensuximide administration (0.3 or 0.6 mmol/kg/day, ip) resulted in transient hematuria and proteinuria, but no change in the other renal function parameters studied. Renal morphological changes observed in Fischer 344 rats occurred primarily in proximal tubular cells. Damaged cells were characterized by large vacuoles at the basal infoldings, accumulations of opaque granules, migration of nuclei to the lumenal membranes, occlusion of the lumen and/or loss or the brush border. Morphological damage was more widespread in Fischer 344 rats than in Sprague‐Dawley rats. Areas of focal hemorrhage were observed in ureters and bladders, especially in Fischer 344 rats given phensuximide 0.6 mmol/kg/day. However, morphological effects may be reversible with continued dosing. It was concluded that phensuximide produces mild, transient renal effects in Fischer 344 rats, and that the Fischer 344 rat is suitable model for studying phensuximide‐induced toxicity to the urinary tract.
Chemical and biological monitoring of chronic lead poisoning in the rat. Implications to the assessment of hazard of low‐level lead
Authors: Wigfield Donald C. , Chakrabarti Chuni L. , Wright Sandra C. , Eastwood Jennifer A. , Karkowska Regina , Johnson Pam M. 
Published: October 2006

AbstractA studyon rats of the effects of lead on δ‐aminolevulinate dehydratase (ALA‐D) activity, and its pH‐dependent maximal enzyme activity is reported. Over a 5‐week period, the lead burden and ALA‐D activity in kidney, liver and brain are documented. Lead concentrations in the organs, expressed as μg/g protein are in the sequence kidney>liver> brain and reach essentially a constant level after 3 days of exposure. This is consistent with the existence of an efficient mechanism removing lead from these organs. Lead affects the ALA‐D in all three organs by reducing the activity and shifting the pH of maximum enzyme activity to more acidic values. In common with the lead levels, the ALA‐D activity does not deteriorate beyond the levels reached after 3 days of exposure. The existence of a mechanism removing lead from the organs is further supported in a recovery study on blood and kidney, in which both lead level and ALA‐D activity return essentially to normal values after 7 days of no exposure to lead.
The preventive effect of prednisolone on the adrenal toxicity of cadmium
Authors: Selypes A. , Lorencz R. , Serényi P. 
Published: October 2006

AbstractThe effects of a single dose of 3.3 mg/kg body weight i.p. or of a single dose of 0.2 mg/kg per os of cadmium and prednisolone on the adrenal weight and the thickness of the adrenal cortex were investigated in female mice. A significant increase was detected in the mean weight of the adrenals and the thickness of the adrenal cortex was signficantly higher than the control value on days 1–3 following cadmium treatment. A. dramatic decrease was observed in both adrenal weight and adrenal cortex thickness on day 4 following cadmium administration. No significant change occurred in the adrenals when prednisolone was given orally to mice following cadmium administration. This observation indicates a protective action of prednisolone on cadmium‐induced adrenal toxicity.
Studies on the mechanism of toxicity of the mycotoxin, sporidesmin. V. Generation of hydroxyl radical by sporidesmin
Authors: Munday R. 
Published: October 2006

AbstractSporidesmin, the mycotoxin responsible for ‘facial eczema’ in ruminants, has previously been shown to generate superoxide radical and hydrogen peroxide. In the present study, the formation of the third ‘active oxygen’ species, hydroxyl radical, has been demonstrated. This species is produced both during the autoxidation of the reduced (dithiol) form of the mycotoxin and in the cyclic reduction/autoxidation reaction between sporidesmin and glutathione. In view of the exceptional reactivity of the hydroxyl radical, this substance may be the proximate agent responsible for the toxic effects of sporidesmin.
Acute toxicity of the major alkaloids of cultivatedLupinus angustifoliusseed to rats
Authors: Petterson D. S. , Ellis Z. L. , Harris D. J. , Spadek Z. E. 
Published: October 2006

AbstractThe seed of modern cultivars ofLupinus angustifoliusnormally contain less than 0.03% alkaloids. The acute oral LD50to rats of a prorata mixture of the alkaloids ofL. angustifoliusseed was found to be 2279 mg/kg. For lupanine the LD50by oral administration was 1464 mg/kg and by intraperitoneal injection 177 mg/kg. For 13‐hydroxylupanine the LD50by intraperitoneal injection was 199 mg/kg. Since these two alkaloids comprise about 85% of the total and are known to be rapidly cleared from the body it is suggested that the alkaloids in this species do not pose a health problem for man.
Oral toxicity of trichlorobenzyl chloride and its acid derivative
Authors: Johannsen Frederick R. , Levinskas George J. 
Published: October 2006

AbstractThe acute rat oral LD50 of 2,4,6‐Trichlorobenzyl chloride (TCBC) was determined to be 3075 mg/kg. When male and female rats were administered 1500 and 3000 ppm TCBC in the diet for 3 weeks, marked retardation in weight gain was observed. Reductions in food consumption were noted in both groups of treated male, but not female, rats. All blood chemistry and urinalysis parameters including those indicative of liver injury, were within the range of normal limits. Gross necropsy revealed pale livers in all high‐dose rats and the majority of low‐dose animals. Gross observations correlated with observation of degenerative hepatic changes (irregularity of cell and nuclear size, cord pattern, edema and cytoplasmic alterations) following microscopic evaluation. Rats and dogs administered up to 100 ppm trichlorobenzoic acid (TCBA) in the diet for 90 days exhibited no effects considered related to treatment.
Structure‐nephrotoxicity relationships for meta‐substituted N‐phenylsuccinimides
Authors: Yang David J. , Brown Patrick I. , Lo Herng‐Hsiang , Teets Vonda J. , Rankin Gary O. 
Published: October 2006

AbstractThe N‐phenylsuccinimides are being evaluated as experimental agricultural fungicides. The purpose of this study was to examine the relationship between the electron withdrawing or electron donating properties of phenyl ring substituents on meta‐substituted N‐phenylsuccinimide (NPS) derivatives and the nephrotoxic potential of the corresponding fungicides. Male Fischer 344 rats were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg), and renal function monitored at 24 and 48 hr. Non‐halogen‐substituted NPS derivatives produced little evidence of nephrotoxicity at the doses used in this study. Among the meta‐halogen derivatives of NPS, N‐(3‐chlorophenyl)succinimide (NCPS) was the most nephrotoxic. NCPS‐induced nephrotoxicity was characterized by diuresis, proteinuria, hematuria, elevated blood urea nitrogen (BUN) concentration, decreased organic ion accumulation and proximal tubular necrosis. However, all renal effects produced by NCPS were mild to moderate. These results suggest that the electron withdrawing or donating property of a functional group is not a good predictor of the nephrotoxic potential for the corresponding fungicide. In addition, lipophilicity did not correlate with nephrotoxic potential for the meta‐substituted NPS derivatives evaluated in this study.
Effects of the exposure profile on the inhalation toxicity of carbon tetrachloride in male rats
Authors: Bogers M. , Appelman L. M. , Feron V. J. , Beems R. B. , Notten W. R. F. 
Published: October 2006

AbstractTo examine the effect of the exposure pattern on the inhalation toxicity of carbon tetrachloride (CCI4) two 4‐week inhalation studies with this compound were carried out in male rats at basic exposure concentrations of 63 and 80 ppm and basic exposure periods of 6 hours per day, 5 days per week. The two main variables studied were interruption of the daily 6‐hour exposures by 1.5 hours (2 × 3‐hour exposures with a non‐exposure interval of 1.5 hour), and peak loads of 5–7 times the basic concentration with or without 1.5‐hour interruption of the daily 6‐hour exposures. Adverse effects of CCI4 included abnormal activities of several enzymes in serum and liver, decreased quantity of microsomal proteins in the liver, increased relative liver weight, and hydropic and fatty degeneration of hepatocytes. As compared with uninterrupted, interrupted exposures increased more the activities of glutamic oxalacetic and glutamic pyruvic transaminase in serum; peak exposures only slightly affected these enzyme activities. Uninterrupted exposures caused less severe fat accumulation in and hydropic degeneration of liver cells than interrupted exposures with or without peak loads. In addition, uninterrupted exposure to 63 ppm CCI4 with peak loads resulted in more severe hydropic liver degeneration than uninterrupted exposure to the same concentration without peak loads. It was concluded that interruption of the daily 6‐hour exposures by 1.5 hour did not result in less severe but rather in slightly more severe hepatotoxicity, and peak loads superimposed on a fixed concentration only slightly aggravated the toxic effects of CCI4 on the liver.
The effects of cardioteratogenic doses of caffeine on cardiac function in the 3‐day chick embryo
Authors: Bruyere Harold J. , Michaud Bernard J. , Gilbert Enid F. , Folts John D. 
Published: October 2006

AbstractThe effects on embryonic cardiac function of caffeine administration (two non‐cardioteratogenic and two cardioteratogenic doses) to Hamburger–Hamilton stage 19 (3–3 1/2 days of incubation) chick embryos were investigated. Using microcinephotoanalysis, we have determined that caffeine (1.0–4.7 mg/egg), within the initial three hours after treatment, produced a dose‐dependent decrease in end diastolic volume, stroke volume, cardiac output, and ejection fraction. These effects were sustained for a longer period of time following dosing at a cardioteratogenic level (3.5–4.7 mg/egg). Caffeine (1.0–4.7 mg/egg) also increased cardiac rate with a maximum increase of 30% seen 60 minutes after treatment with doses of 2.7 mg and 3.5 mg. However, the increase in cardiac rate was not related to dose. At 20 hours after treatment, caffeine increased stroke volume, ejection fraction and cardiac output relative to the controls. End‐diastolic volume and cardiac rate were not changed. These results are evidence for a biphasic effect of cardioteratogenic dosing with caffeine during the first 20 hours after treatment—initially a sustained decrease in cardiac output, suggesting decreased flow through the embryonic heart, followed by an increase in ejection fraction, suggesting increased cardiac workload.
Effects of methyl mercury and cadmium on the kinetics of substrate activation of (K+)‐paranitrophenyl phosphatase
Authors: Sahib K. I. Ahammad , Moorthy K. S. , Desaiah D. 
Published: October 2006

AbstractPrevious studies from this laboratory have indicated that methyl mercuric chloride (CH3HgCI) and cadmium chloride (CdCI2) are potent inhibitors of K+‐p‐nitrophenyl phosphatase (K+‐PNPPase). The present studies were undertaken to study the effects of CH3HgCI and CdCI2 on the substrate activation kinetics of K+‐PNPPase to understand the mechanism of inhibition of Na+ pump by these heavy metals. Uncompetitive inhibition with regard to activation by PNPP was indicated by altered Vmax and Km values by both the heavy metals. Substrate activation kinetics of heavy metal inhibited K+‐PNPPase in the presence of 25 μM dithiothreitol and glutathione indicated mixed type of activation by altering apparent Vmax and Km. Absence of competition between PNPP site and heavy metals appear to indicate absence of reactive‐SH groups in the active site. Failure of added iodoacetate, in concentrations ranging from 5 × 10−8 to 5 × 10−5M, to inhibit K+‐PNPPase further substantiate this conclusion. The results suggest that CH3HgCI and CdCI2 inhibit Na+ pump by inducing conformational changes in the enzyme and thereby decrease catalytic velocity of dephosphorylation of the enzyme‐phosphoryl complex. Hydrolysis of PNPP was linear with time with or without either heavy metal and the inhibition exerted by CH3HgCI or CdCI2 on free or heavy metal loaded enzyme indicated absence of heavy metal interaction. The results suggest that CH3HgCI and CdCI2 inhibit K+‐PNPPase possibly by binding at two different sites.
Toxicological profile of orally administered 1,6‐hexane diamine in the rat
Authors: Johannsen Frederick R. , Levinskas George J. 
Published: October 2006

AbstractThe industrial chemical 1,6‐Hexane Diamine, or hexamethylenediamine (HMD), has an acute oral LD50 of 980 mg kg−1 in rats. Dietary administration of HMD to groups of rats for 3 months at dosages of 0, 50, 150, and 500 mg kg−1 resulted in a modest retardation in weight gain at the two higher test levels. No other obvious signs of toxicity or changes in the peripheral blood picture or selected clinical pathology parameters were found at any test level throughout the study. Evaluation of absolute and relative weights of 10 selected organs, as well as complete necropsies and microscopic evaluation of over 30 selected tissues and organs, revealed no changes considered related to treatment. The administration of HMD by gavage to pregnant rats at 0, 112, 184 and 300 mg kg−1 day−1 on days 6–15 of pregnancy (day 1 = day sperm detected) did not induce any teratogenic effects. Signs of maternal toxicity were observed only at 300 mg kg−1 day−1. Embryotoxicity was observed at both the 300 and 184 mg HMD kg−1 day−1 dosage levels. No treatment‐related effects were observed at 112 mg HMD kg−1 day−1.
Role of exposure parameters in toxicity of aerosolized diesel fuel in the rat
Authors: Dalbey W. , Henry M. , Holmberg R. , Moneyhun J. , Schmoyer R. , Lock S. 
Published: October 2006

AbstractSprague–Dawley rats were exposed to aerosolized diesel fuel (ADF) to determine the potential health effects in military troops during exposure to this visual obscurrant. Acute range finding studies were performed to estimate exposure conditions at which minimal (<1%) mortality would occur. This information was used in the design of a repeated exposure study to test the relative significance of the frequency of exposures, the duration of exposure, and aerosol concentration in any toxicity which might occur. Animals were exposed once or three times per week for a total of nine times to concentrations ranging from 1.3 mg ADFI−1 to 6 mg ADFI−1 and exposure durations of 2 or 6 h. Body weight and food consumption were recorded at weekly intervals during the exposure period and in animals that were retained for 2 weeks after the last exposure. Animals were used for a variety of endpoints, including neurotoxicological tests, pulmonary function tests, hematology, clinical chemistry, organ weights, and histopathology, either within 2 days of the last exposure or after the 2‐week recovery period. Animals exposed to ADF showed an initial depression in body weight followed by a slower rate of growth than the sham exposed controls. No exposure related changes were observed in any of the neurotoxicology assays. The lung was the primary site of toxicity. Focal accumulations of pulmonary free cells were observed histologically, with thickening and hypercellularity of nearby alveolar walls. The number of lavaged pulmonary free cells increased similarly. Both pulmonary wet and dry weights increased. Lung volumes were altered by exposure, including increased FRC and decreased TLC. Carbon monoxide diffusing capacity was decreased. Histologic abnormalities were not observed in any other organs. Of the exposure parameters tested, the frequency of exposure appeared to be the most significant in relation to degree of toxicity.