bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of deferrioxamine and diethyldithiocarbamate on paracetamol‐induced hepato‐ and nephrotoxicity. The role of lipid peroxidation
Authors: Younes Maged , Sause Christiane , Siegers Claus‐Peter , Lemoine Robert 
Published: October 2006

AbstractIn mice subjected to glutathione depletion by pretreatment with phorone (diisopropylidene acetone, 200 mg/kg i.p. in 10 ml/kg olive oil) paracetamol (acetaminophen, 300 mg/kg p.o. in 10 ml/kg tylose 2 h later) led to a marked hepatotoxicity as evidenced by increased plasma activities of the liver‐specific enzymes sorbitol dehydrogenase (SDH) and glutamate‐pyruvate‐transaminase (GPT) 3 and 24 h after treatment. Nephrotoxicity was also indicated at both timepoints by an increased creatinine concentration in plasma, while neither the urine volume nor its content in γ‐glutamyl transpeptitase over 20 h were affected. Hepato‐ and nephrotoxicity were also assessed histomorphologically. In vivo lipid peroxidation (LPO), as measured by ethane exhalation over 3 h, was clearly enhanced by paracetamol. Malondialdehyde content was increased and glutathione concentration diminished in the liver, but not in the kidney. Diethyldithiocarbamate (DTC, 200 mg/kg i.p.) or deferrioxamine (DFO, 500 mg/kg i.p.) both given 30 min before PA, inhibited in vivo LPO. However, only DTC was capable of antagonizing the hepato‐ and nephrotoxic effects of paracetamol, while DFO only delayed the onset of nephrotoxicity but left the hepatotoxicity unaffected. Both agents inhibited the rise in hepatic malondialdehyde‐content, but only DTC prevented paracetamol‐induced glutathione depletion. These results indicate that LPO is not mainly responsible for paracetamol toxicity towards liver or kidney.
Do cage effects influence tumor incidence? An examination of laboratory animal carcinogenicity studies utilizing fischer 344 rats
Authors: Haseman Joseph K. 
Published: October 2006

AbstractApproximately 125 carcinogenicity studies in Fischer 344 rats conducted by the National Toxicology Program (NTP) were examined to determine the frequency with which cage effects were associated with observed carcinogenic responses. All studies involving groups of 50 rats housed five per cage and showing evidence of chemically‐related carcinogenicity were considered. For each of these experiments, two statistical analyses were carried out for each dosed and control group: (i) a test to determine whether or not the occurrence of tumors clustered within cages; and (ii) an evaluation to determine whether or not tumor incidences differed significantly between differing cage shelf levels. These analyses showed that the numbers of statistically significant (P < 0.05 or P < 0.01) effects were consistent with the number expected by chance alone. Thus, cage‐related factors appeared to have little or no impact upon tumor incidence in these particular studies. Experimental design protocols now used by the NTP (which include random assignment of animals to cages; random assignment of columns of cages to dosed and control groups; and periodic rotation of cage location) further reduce the likelihood that factors associated with the housing of the animals could influence tumor incidence in current studies.
Three‐generation reproduction study with caprolactam in rats
Authors: Serota David G. , Hoberman Alan M. , Friedman Marvin A. , Gad Shayne C. 
Published: October 2006

AbstractIn a three‐generation reproduction study, rats were given caprolactam in the diet of 0, 1000, 5000 and 10,000 ppm. No treatment‐related effects were observed in the parental animals with respect to mortality, clinical signs, reproductive performance or gross pathology findings. Consistently lower body weights were noted in the P2 and P3 mid‐ and high‐dose males and females. Consistently lower mean food consumption values were noted in the P2 and P3 mid‐ and high‐dose males and the high‐dose females. These differences were generally significant (P ≤ 0.05) in the high‐dose group of both sexes. Compound‐related histopathologic findings noted in the high‐dose P1 males consisted of a slight increase in the severity of spontaneous nephropathies, occasionally accompanied by granular casts. The offspring data revealed no treatment‐related effect with respect to gross appearance, gross pathology, survival, number of pups, percentage of male pups or kidney weight. Analysis of the offspring body weights on Days 1, 7 and 21 of lactation revealed consistently and generally significant lower mean values in the high‐dose male and female animals of all filial generations. The mean body weights of both sexes in the mid‐dose group were generally lower than those of the controls. The effects on mean body weight, mean food consumption and the group increases in the severity of nephropathy, accompanied by the presence of granular casts in some animals, are considered to be related to the administration of caprolactam.
Effectiveness of chelation therapy with time after acute vanadium intoxication
Authors: Gómez M. , Domingo J. L. , Llobet J. M. , Paternain J. L. 
Published: October 2006

AbstractThe effect of increasing the time interval between vanadium exposure and chelation therapy was studied in male Swiss mice. The following chelating or reducing agents were administered i.p. at 0, 0.5, 2 and 8 h after i.p. administration of 0.16 mmol kg−1 sodium metavanadate: ascorbic acid, deferoxamine mesylate (DFOA) and 4,5‐dihydroxy‐1,3‐benzene‐disulphonic acid (Tiron). These agents were given at doses equal to one‐quarter of their respective LD50 values. Daily elimination of vanadium into urine and faeces was determined for four days. The excretion of vanadium was especially rapid in the first 24 h. Treatment with Tiron increased significantly the urinary elimination of vanadium in all four groups during Day 1, whereas DFOA significantly increased the faecal excretion during the same period. Treatment with DFOA or Tiron resulted in a significant decrease in the concentration of vanadium in the kidney four days after sodium metavanadate administration. The magnitude of the increased elimination of vanadium, as well as the decreased tissue concentration of the metal, was remarkably attenuated by increasing the time interval between vanadium injection and administration of the chelators.
Effect of iron overload on spontaneous and xenobiotic‐induced lipid peroxidation in vivo
Authors: Younes M. , Eberhardt I. , Lemoine R. 
Published: October 2006

AbstractTo study the effect of iron‐overload on hepatic lipid peroxidation, two rat models of haemochromatosis were employed: in the first model resembling secondary haemochromatosis, repeated i.p. injections with Fe‐dextran led to an accumulation of Fe in Kupffer cells, while in the second model resembling hereditary haemochromatosis, iron was located mainly in periportal hepatocytes after feeding on a diet containing 3.5% Fe‐fumarate for 3 weeks. In both models, total hepatic iron content was elevated four‐ to fivefold over controls. In vivo lipid peroxidation (ethane exhalation) was enhanced only in the second model, indicating that the hepatocytes are the main targets of Fe‐induced lipid peroxidation. Low hepatotoxicity was observed in the second model. Additional treatment of the rats with hepatotoxic agents led to different results: with ethanol and bromobenzene, lipid peroxidation was only evident in both models of iron‐overload, while paracetamol‐induced lipid peroxidation was seen only in Fe‐fumarate‐fed rats. CCl4‐induced lipid peroxidation was strongly enhanced in both models of haemochromatosis. Hepatotoxicity was enhanced by iron overload only in the case of CCl4 treated, Fe‐fumarate‐fed rats. The activities of phase I and phase II enzymes of xenobiotic metabolism were not markedly altered in livers of iron‐overloaded rats. This implies that neither the bioactivation nor the detoxification of the agents studied were affected in experimental haemochromatosis.
Specific determination of bromobenzene metabolites by high‐performance liquid chromatography
Authors: Truchon G. , Brodeur J. , Gérin M. 
Published: October 2006

AbstractA chromatographic method for the quantitative and simultaneous determination of phenolic and mercapturic acid type metabolites of bromobenzene is presented. Acid hydrolysis (1.5 N HCI, 100°C, 10 min) yielded unconjugated bromophenols. After extraction (ethyl acetate, pH 2), evaporation to dry ness and dissolution in methanol, samples were analysed by high‐performance liquid chromatography (HPLC) with a c18 reverse‐phase column and a phosphate buffer (0.1 M,pH 9 + 5 mM tetrabutylammonium dihydrogen phosphate) — acetonitrile gradient with ultraviolet detection (225 nm). Benzylmercapturic acid and o‐chlorophenol were used as internal standards. Using this method, it was possible to determine simultaneously o, m‐ and p‐bromophenols together with o‐, m‐ and p‐bromophenylmercapturic acids. Additional validation data were obtained by analysis of urine samples from rats treated with bromobenzene. This new method was compared to existing procedures.
Effects of vinyl chloride on liver function of exposed workers, evaluated by measurements of plasma clearance of the 99Tc–N‐2,4‐dimethylacetanilido‐iminodiacetate complex
Authors: Studniarek Michał , Durski Krzysztof , Liniecki Julian , Brykalski Dariusz , Poznańska Anna , Głuszcz Maria 
Published: October 2006

AbstractIn 77 males exposed occupationally to vinyl chloride (VC), the plasma clearance (Cl) of 99Tc–N(2,4‐dimethylacetanilido)iminodiacetate (‘HEPIDA’ complex) was determined. The results were juxtaposed with a scaled assessment of liver parenchyma performance based upon clinical examination and a series of biochemical tests. Detection of the diagnosable damage of liver parenchyma by means of the reduced clearance was sensitive (90%) at the reasonable specificity of 74%. Probability of exclusion of liver damage in patients with the clearance above 240 ml min−1 1.73 m−2 amounted to 92%.There was a significant correlation between degree of exposure to VC and the frequency of low clearance values.It appears that the periodic determination of the 99Tc–HEPIDA clearance in workers exposed to VC allows the assessment of incipient liver damage and signals the need for prophylactic measures.
A rapid digestion method for analysis of nickel compounds in tissue by electrothermal atomic absorption spectrometry
Authors: Benson Janet M. , Eidson Arthur F. , Hanson Ray L. , Henderson Rogene F. , Hobbs Charles H. 
Published: October 2006

AbstractQuantification of nickel in animal soft tissue is of toxicological interest. A digestion method applying the use of microwave ovens for irradiating samples in Teflon digesters was developed. An acid mixture containing nitric acid (16 M, 1.0 ml g−1 tissue), hydrochloric acid (6 M, 0.5 ml g−1 tissue) and H2O2 (30%, 1.0 ml g−1 tissue) and irradiation at 600 W for 5 min were required for complete dissolution of tissue matrices and nickel compounds. Analyses of Ni in National Bureau of Standards Reference Material 1566 oyster tissue gave 0.87 ± 0.24 μg g−1 (mean ± SD, n = 5), which was in agreement with the NBS certified value of 1.03 ± 0.19 μg g−1. Recoveries of 1–300 μg Ni added as nickel sulfate (highly soluble), nickel subsulfide (moderately soluble in biological fluids and acid) or nickel oxide (green high‐temperature oxide, low solubility in biological fluids and acid) to lung, liver, lymph node and kidney were quantitative, except in the case of nickel sulfate added to kidney, where recovery was less than quantitative for 1–10 μg Ni. The method appears effective for digestion of a variety of tissues requiring Ni analyses.
3‐Hydroxypropylmercapturic acid: A biologic marker of exposure to allylic and related compounds
Authors: Sanduja Radhika , Ansari G. A. S. , Boor Paul J. 
Published: October 2006

Abstract3‐Hydroxypropylmercapturic acid [3‐OHPrMCA, S‐(3‐hydroxypropyl)‐N‐acetyl‐‐l‐‐cysteine] was quantitatively measured by high‐performance liquid chromatography (HPLC) in the urine of rats given allylamine‐HCl (5, 25, 50, 100 and 150 mg kg−1), acrolein (13 mg kg−1), allylalcohol (64 mg kg−1), allylchloride (76 mg kg−1), allylbromide (120 mg kg−1), allylcyanide (115 mg) and cyclophosphamide (160 mg kg−1) by gavage in water. 3‐OHPrMCA was measured by HPLC in 24‐h urine collections; the lower detection limit was 1.25 μg or 5.6 nmol ml−1. Various doses of allylamine resulted in 3‐OHPrMCA excretion at a fairly constant percentage of the dose, ca. 44–48% at 0–24 h and 3% at 24–48 h, indicating rapid metabolism through glutathione conjugation in the first 24h. Similarly, 3‐OHPrMCA was recovered in the urine of rats given acrolein (78.5%), allylalcohol (28.3%), allylchloride (21.5%), allylbromide (3.0%), allylcyanide (3.7%) and cyclophosphamide (2.6%). These data indicate that 3‐OHPrMCA can be used as a marker of exposure to allylic and other compounds that lead to the metabolic formation of acrolein.
Complex mixture effects on the dermal absorption of benzo[a]pyrene and other polycyclic aromatic hydrocarbons from mouse skin
Authors: Dankovic David A. , Wright Cherylyn W. , Zangar Richard C. , Springer David L. 
Published: October 2006

AbstractTo study the dermal penetration of benzo[a]pyrene (BAP) in relation to other polycyclic aromatic hydrocarbons (PAHs), a complex mixture of PAHs was applied to the backs of CD‐1 mice, and the dermal residence times of BAP and eleven other PAHs were determined using gas chromatography. The dermal penetration of BAP was found to be representative of the other PAHs studied, with a dermal half‐life of 6.7 h. Half‐lives of the other eleven PAHs ranged from 5.0 to 8.8 h. The dermal half‐life of BAP applied in a volatile organic solvent, rather than a PAH mixture, was 3.0 h. The effects of five complex organic mixtures, with boiling points ranging from 300–700°F to >850°F, on the dermal residence time of BAP was studied by adding radiolabeled BAP to the mixtures, and applying them to the backs of mice. All of the mixtures studied increased the dermal residence time of BAP by amounts ranging from 1.8‐fold to 6.9‐fold.
Sebaceous gland suppression as a short‐term test of the cutaneous carcinogenic activity of mineral oils
Authors: Peristianis G. C. 
Published: October 2006

AbstractForty‐seven mineral oils were tested for their ability to induce sebaceous gland suppression in female C3H/HeN or CF1 mice. Six groups of five mice were treated with zero, one, two, three, four or six epidermal applications of one or more of three volumes (0.2, 0.1 or 0.05 ml) of the test substance. The sebaceous gland suppression indices were calculated from the total numbers of sebaceous glands and hair follicles in nine sections of treated skin from each mouse. Suppression curves were drawn by plotting the mean suppression indices against the number of applications of each oil sample.The suppression curves were compared with the cutaneous carcinogenic potentials of these mineral oils, assessed by long‐term skin bioassays. All the carcinogenic oil samples induced suppression of sebaceous glands. The non‐carcinogenic samples had no significant suppressant activity. There was a correlation between cutaneous carcinogenic activity and suppressant potential for all tested samples. Results of the suppression tests considered, together with the kinematic viscosities of the test substances, enabled accurate prediction of their cutaneous carcinogenic potential.
Renal handling of 2‐methyl‐4‐chlorophenoxyacetic acid (MCPA) in rats
Authors: Bräunlich Helmut , Bernhardt Heike , Bernhardt Ingo 
Published: October 2006

AbstractFollowing i.p. administration of various doses of 2‐methyl‐4‐chlorophenoxyacetic acid (MCPA), ca. 50% is excreted during a 5‐h diuresis experiment. After i.p. administration of MCPA, virtually no distribution occurs (Vrel = 18% of the body weight). Renal excretion of MCPA can be accelerated by inhibition of its renal tubular reabsorption. The distinct inhibition of renal excretion of MCPA by simultaneous administration of probenecid or p‐aminohippurate (PAH) indicates the active tubular transport of MCPA; this transport process can be stimulated by treatment of rats with triiodothyronine. Active tubular transport of MCPA was confirmed by measurement of MCPA accumulation in renal cortical slices, both under aerobic and anaerobic conditions. Accumulation of MCPA under anaerobic conditions indicates an additional passive uptake and binding of MCPA in kidney tissue in accordance with the high degree of binding to plasma albumin (85%).
Metal inhibition of calmodulin activity in monkey brain
Authors: Vig P. J. S. , Nath R. , Desaiah D. 
Published: October 2006

AbstractStudies were conducted to investigate the effect of vanadium (V5+), cadmium (Cd2+), mercury (Hg2+), aluminium (Al3+), lead (Pb2+) and manganese (Mn2+) ions on calmodulin (CaM)‐related Ca2+‐ATPase activity in rhesus monkey (Macaca mulatta) brain (RMB). The cerebral cortex of RMB was dissected and homogenized in 10% sucrose buffer, and synaptic plasma membranes (SPM) were prepared. Ca2+‐ATPase activity was determined by the inorganic phosphate method. Different concentrations of metal ions were incubated with RMB fractions containing endogenous CaM and RMB fractions without CaM. The results show that no metal ion inhibited the basal enzyme but that they showed a profound inhibition of total Ca2+‐ATPase containing CaM. The order of potency of metals was Hg>Cd>Pb>Mn>Al>V. Exogenous addition of CaM restored the metal‐inhibited enzyme activity to near the normal level. The basal enzyme, when reconstituted with CaM, showed sensitivity to metal ions. These data, presented for the first time in non‐human primate brain, indicate that the metal ions inhibit CaM activity in RMB.
A comparison of the effects of dietary cadmium on heart and kidney antioxidant enzymes: Evidence for the greater vulnerability of the heart to cadmium toxicity
Authors: Jamall I. Siraj , Naik Malini , Sprowls J. J. , Trombetta L. D. 
Published: October 2006

AbstractThis study demonstrates the greater susceptibility of the heart as compared to the kidney to cadmium in the presence of high dietary selenium. Male weanling rats were fed an adequate‐copper low‐selenium feed supplemented with 0, 10 or 50 ppm copper with or without 50 ppm dietary cadmium for 7 weeks. All rats received 0.5 ppm selenium in their drinking water. Cadmium treatment resulted in histopathological lesions in the heart, but not in the kidney. Although cadmium treatment resulted in more extensive effects on glutathione peroxidase and superoxide dismutase in the heart as compared to the kidney, no increase in peroxidation was noted in either organ, suggesting that cadmium cardiotoxicity can be dissociated from tissue peroxidation. Mean cadmium concentrations in the heart ranged from 0.55 to 1.22 μg cadmium g−1 tissue, wet weight, and in the kidney from 11.53 to 21.04 μg cadmium g−1 tissue, wet weight, and in the kidney from 11.53 to 21.04 μg cadmium g−1 tissue, wet weight. In both tissues examined, cadmium levels were influenced by dietary copper and heart cadmium concentrations did not correlate with either the biochemical or histological lesions observed. Thus, tissue cadmium levels alone may not be adequate for predicting cadmium toxicity.
Dose and time effects of combined exposure to lead and ethanol on lead body burden and some neuronal, hepatic and haematopoietic biochemical indices in the rat
Authors: Tandon Sushil K. , Flora Swaran J. S. 
Published: October 2006

AbstractEthanol (1, 2 or 5 g kg−1) and lead (0.55 g I−1 in drinking water) were given either alone or in combination for 4 months to rats. The uptake of lead in tissues, some lead‐sensitive variables, the levels of biogenic amines in different brain regions, hepatic lipid peroxidation, glycogen and blood glucose concentrations were measured.Ethanol or lead when given alone inhibited the activity of blood δ‐aminolevulinic acid dehydratase (ALAD). The co‐administration of 5 g kg−1 but not 1 or 2 g kg−1 ethanol significantly enhanced the lead‐induced inhibition of blood δ‐ALAD activity and the elevation of δ‐aminolevulinic acid (ALA) excretion. Co‐exposure to lead and ethanol (5 g kg−1) produced a more pronounced increase in hepatic lipid peroxidation and blood glucose level than either ethanol or lead alone. This combination also caused a significant increase in the dopamine (DA) contents of striatum, midbrain and pons medulla, norepinephrine (NE) contents in midbrain and 5‐hydroxytryptamine (5‐HT) contents of hypothalamus, striatum, midbrain and pons medulla over levels produced by lead alone. However, the level of NE in hypothalamus decreased upon co‐administration. The uptake and retention of lead was significantly higher in blood, liver, kidney and brain in animals co‐exposed to lead and 5 g kg−1 ethanol. Blood and kidney lead was also increased by 2 g kg−1 ethanol. The results suggest that prolonged and heavy consumption of alcohol may increase the toxicity of lead.
Evaluation of the teratogenic potential of the rubber accelerator dibenzthiazyl disulphide in rats
Authors: Ema Makoto , Sakamoto Jun , Murai Toshimi , Kawasaki Hironoshin 
Published: October 2006

AbstractThe teratogenic potential of dibenzthiazyl disulphide (MBTS) was studied in Wistar rats. Pregnant rats were given MBTS at a dosage of 0, 0.04, 0.2 or 1% in the diet from day 0 to day 20 of pregnancy. Daily intakes of MBTS were 26 mg kg−1 for the 0.04% group, 127 mg kg−1 for the 0.2% group and 596 mg kg−1 for the 1% group. Maternal body weight gain during day 0 to day 14 of pregnancy in the 1% group was significantly lowered, but no significant changes induced by MBTS were observed in any other maternal parameters, such as food consumption and clinical sign of toxicity. There were no significant compound‐related effects on the incidences of pre‐ and postimplantation losses and the number, sex ratio and body weight of live fetuses. Morphological examinations of the fetuses revealed no evidence of teratogenesis. In the postnatal development of the offspring from the dams given MBTS, a high survival rate and good growth of the offspring were seen. It could be concluded that MBTS possesses no adverse effects on the pre‐ and postnatal development of the offspring in rats at the doses employed in the present study.
A rapid bioassay for chemicals that induce pro‐oxidant states
Authors: Knobeloch L. M. , Blondin G. A. , Lyford S. B. , Harkin J. M. 
Published: October 2006

AbstractA new bioassay has been developed that allows rapid, sensitive detection of chemicals such as paraquat and adriamycin, which manifest their acute toxicity, mutagenicity or carcinogenicity by inducing a pro‐oxidant statein vivo.Submitochondrial particles isolated from bovine myocardium are used to catalyze NADH‐dependent enzymatic reduction of these chemicals to free radicals. The highly reactive species generated in this system reduce molecular dioxygen to the superoxide anion radical, which is detected spectrophotometrically using the adrenochrome reaction. The anticancer drug adriamycin, the herbicides paraquat and diquat, the analytical dye sulfonazo III, and the experimental carcinogen 4‐nitroquinoline‐N‐oxide have been used to test the sensitivity of this new method. This assay can be used to screen fresh water samples for the presence of pollutants that can generate oxygen‐centered free radicalsin vivo, or to test newly synthesized chemicals for this activity, and may therefore be valuable for environmental monitoring and preliminary toxicity evaluation of industrial or pharmaceutical products.