bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertrophy and hyperplasia of the rat pancreas produced by short‐term dietary administration of soya‐derived protein and soybean trypsin inhibitor
Authors: Smith J. C. , Wilson F. D. , Allen P. V. , Berry D. L. 
Published: October 2006

AbstractFeeding soy protein concentrate to weanling rats over a one‐week period produced a dose‐related increase in pancreatic weight due to an increase in acinar cell size. Hyperplastic changes occur simultaneously, as evidenced by an increase in mitotic activity after two days on the test diet. Similar changes were also obtained by feeding soybean Kunitz trypsin inhibitor over the same time period. The results suggest that this approach may be useful as a model to investigate the effect of plant‐derived material on the pancreas, in particular proliferative lesions.
Peroxidative Damage and Nephrotoxicity of Dichlorovinylcysteine in Mice
Authors: Beuter W. , Cojocel C. , Müller W. , Donaubauer H. H. , Mayer D. 
Published: October 2006

AbstractMale NMRI mice were treated i.p. with dichlorovinylcysteine (DCVC) in a dosage of 2.5‐500 mg/kg−1 and renal cortical slices from naive mice were incubated with 0–125 μg/ml−1 DCVC. The effects of DCVC on blood urea nitrogen (BUN), reduced glutathione (GSH) content, malondialdehyde (MDA) production, p‐aminohippuric acid (PAH)‐ and tetraethylammoniun (TEA)‐accumulation and glucose synthesis (gluconeogenesis) were measured.DCVC depleted GSH in a time‐ and dose‐dependent manner. Depletion of renal cortical GSH by DCVC was more pronounced in the kidney cortex than in the liver. DCVC caused a dose‐dependent increase of ethane exhalation and of MDA production in the renal cortex. When animals were kept in a closed system, decrease in oxygen concentration increased the peroxidative damage. No increase of MDA concentration was observed in the liver. Treatment of mice with DCVC induced a dose‐dependent increase in BUN and decreased the accumulation of PAH and TEA in renal cortical slices. Pretreatment of mice with aminooxyacetic acid (AOAA) and (+) cyanidanol‐3 (CY) caused a significant reduction in DCVC‐induced lipid peroxidation and nephrotoxicity. In vitro incubation of renal cortical slices of naive mice with DCVC resulted in a concentration‐dependent increase in MDA and a concentration‐dependent decrease in the accumulations of PAH, TEA and of gluconeogenesis.In conclusion, the interaction of DCVC and/or its metabolites with membrane lipids may be responsible for lipid peroxidation and nephrotoxicity. The formation of lipid peroxidation products was greater under hypoxic conditions and appeared to be related to the DCVC‐induced nephrotoxicity. This data suggests lipid peroxidation as a possible mechanism of DCVC‐induced nephrotoxicity.
Evaluation of the teratogenic potential of the rubber accelerator N‐cyclohexyl‐2‐benzothiazylsulfenamide in rats
Authors: Ema Makoto , Murai Toshimi , Itami Takafumi , Kawasaki Hironoshin , Kanoh Seizaburo 
Published: October 2006

AbstractThe teratogenicity of N‐cyclohexyl‐2‐benzothiazylsulfenamide (CBS) was studied in Wistar rats. Pregnant rats were given CBS at a dosage of 0.001, 0.01, 0.1 or 0.5% in the diet from Day 0 to Day 20 of pregnancy. Daily intakes of CBS were 0.7 mg kg−1 for the 0.001% group, 7.1 mg kg−1 for the 0.01% group, 69.6 mg kg−1 for the 0.1% group and 288.8 mg kg−1 for the 0.5% group. Maternal body weight gain during pregnancy in the 0.1 and 0.5% groups was significantly lowered. Food consumption during pregnancy in the CBS‐treated groups, except for the 0.5% group, did not differ from that in the control group. Neither death nor clinical signs of toxicity were noted in the pregnant females of any group. Lowered weight in fetuses and the placentae were observed in the 0.5% group. There were no significant compound‐related effects on the incidences of pre‐ and post‐implantation losses and the number and ratio of live fetuses. Morphological examinations of the fetuses revealed no evidence of teratogenesis. It could be concluded that CBS possesses no adverse effects on the prenatal development of the offspring in rats at doses employed in the present study.
Characterization of toxicity involving haemorrhage and cardiovascular failure, caused by parenteral administration of a soluble polyacrylate in the rat
Authors: Hicks R. , Satti A. K. , Leach G. D. H. , Naylor I. L. 
Published: October 2006

AbstractAdverse effects, involving a combination of hypotension and widespread haemorrhages, as well as evidence of vascuiiar and other tissue dissociation, associated with various systemic malfunctions (cyanosis, cardiac arrhythmias, neuromuscular disorder and death) were observed in the rat, from parenteral administration of a high‐molecular‐weight soluble polymer, sodium polyacrylate (EN21). Experiments to elucidate the mechanism of this effect involved comparisons with a low‐molecular‐weight sodium polyacrylate (EN5), either drug being given to groups of 5–8 rats, male or female, in doses of 5–100 mg/kg i.v., i.p. or s.c., or up to 100 mg/kg p.o. Effects were observed visually up to the death of the animals, and these plus survivors killed after 10 h were prosected for macroscopic and histopathological examination of internal organs. Characteristic EN21 effects were only observed in animals treated by the i.p. and i.v. routes, death occurring in 4–10 h or rapidly (1 h) after i.v. dosage. No such effects were observed from ENS by any dose or route. There were no differences between effects in male and female animals.In rats anaesthetized with sodium pentobarbitone and cannulated for blood pressure recording (arterial and venous), no hypertensive effects were observed to explain haemorrhagic effects. Instead, i.v. and i.p. injections gave depressor effects, insidious in the latter case, with a precipitous fall only in the delayed terminal stage. Effects were accompanied by cardiac arrhythmias. Depressor effects were prevented by prior treatment of the animals with calcium chloride solution. These effects could not be evoked by EN5, nor by injection of methylcellulose solutions of equivalent high viscosity. It is suggested that, in the absence of pressor effects, haemorrhages must be explained by vascular fragility (angiostaxis), associated with disintegration of other tissues (e.g. intestinal villi). Other malfunctions, too rapid to be dependent on loss of blood, could be explained in terms of hypocalcaemia.It is suggested that localization of this viscous, high‐molecular‐weight material in vascularized compartments, together with its known ability to form insoluble precipitates with calcium, leads to the operation of a calcium ‘sink’. Resulting hypocalcaemia would explain neuromuscular and cardiac malfunctions, while radical loss of tissue calcium could lead to decrease in cellular adhesion. Resultant loss of tissue integrity could be consistent with observed haemorrhage and disintegrative lesions.
Adrenal‐dependent leucopenia after short‐term exposure to various airborne irritants in rats
Authors: Brondeau M. T. , Bonnet P. , Guenier J. P. , Simon P. , de Ceaurriz J. 
Published: October 2006

AbstractLeucopenia without any change in differential or red blood cell counts was observed in rats exposed for 4 h to increasing concentrations of the following airborne irritants: acetic acid, benzyl chloride, 1,2‐dichlorobenzene, ethyl acetate, ethyl acrylate, formaldehyde, isophorone, mesityl oxide, phenol, styrene, toluene diisocyanate and vinyl toluene. This effect was abolished by adrenalectomy. Vinyl toluene and 1,2‐dichlorobenzene induced leucopenia at levels as low as their current occupational standards of 50 ppm. With the exception of 1,2‐dichlorobenzene, the tested compounds caused leucopenia only when exposure reached the irritant level. It is discussed that stress associated with the irritative effect of chemicals can confound specific hacmatological effects.
Oxime‐induced reactivation of acetylcholinesterase inhibited by organophosphinates
Authors: Hanke D. W. , Beckett M. S. , Overton M. A. , Burdick C. K. , Lieske C. N. 
Published: October 2006

AbstractThe comparative potency of oximes for reactivation of inhibited eel acetylcholinesterase (AChE) in vitro is dependent on the organophosphinate inhibitor. Some of the data, dealing with a reference organophosphonate, support the conclusion of other investigators that the oxime potency order is also dependent on the inhibiting phosphonate. This work was done to identify more clearly the nature of phosphinylated AChE with regard to oxime reactivation potency and the potential of phosphinates as pretreatment drugs to protect AChE against organophosphonate poisoning. We have determined the reactivation potency of four oximes—2‐PAM, HI‐6, TMB‐4 and toxogonin—against four phosphinates—4‐nitrophenyl methyl(phenyl)phosphinate (PMP), 4‐nitrophenyl chloromethyl(phenyl)phosphinate (CPMP), 4‐nitrophenyl trifluoromethyl(phenyl) phosphinate and 4‐nitrophenyl bis(2‐thienyl)phosphinate. For comparison, the phosphonate sarin (GB, isopropyl methylphosphonofluoridate) was included. Incubation of the inhibited enzyme (I‐AChE) at 25°C was with 0.30 μM oxime for PMP, 3.0 μM oxime for sarin and CPMP and 100 μM oxime for the two remaining phosphinates. AChE activity was assayed spectrophotometrically for 3.0 min at 272.5 nm at 25°C in 0.10 M MOPS buffer (pH 7.60) using phenyl acetate as substrate. When sarin was the inhibitor (0% spontaneous recovery after a 2‐h incubation), the order of oxime reactivation was 2‐PAM (46%) ⩾ toxogonin (33%) = TMB‐4 (31%) > HI‐6 (9%) after 2‐h incubations. For PMP (12% spontaneous recovery after a 2‐h incubation) the oxime order was toxogonin (67%) > TMB‐4 (53%) > 2‐PAM (40%) after 2‐h incubations. For CPMP (8% spontaneous recovery after a 30‐min incubation) the order was toxogonin (65%) = TMB‐4 (59%) = HI‐6 (57%) > 2‐PAM (12%) after 30‐min incubations. For the trifluorophosphinate the order was toxogonin (18%) = TMB‐4 (17%) > HI‐6 (12%) ⩾ 2‐PAM (3%) after 5‐min incubations. For the bis‐thienylphosphinate the order was HI‐6 (38%) > 2‐PAM (20%) > TMB‐4 (0.4%) > toxogonin (0%) after 5‐min incubations. Despite some uncertainty in the oxime orders, these results support the conclusion that oxime potency is dependent on the organophosphinate used as the AChE inhibitor. The results also broaden the database that underpins the generally accepted conclusion, that for a given oxime its reactivation potency is dependent on the organophosphorous compound used to inhibit AChE.
Desferrioxamine‐induced alterations in hepatic iron distribution, DNA damage and lipid peroxidation in control and 2, 3, 7,8‐tetrachlorodibenzo‐p‐dioxin‐treated rats
Authors: Wahba Z. Z. , Murray W. J. , Stohs S. J. 
Published: October 2006

AbstractDesferrioxamine (DFX), an iron chelator, has been used to inhibit in vitro redox cycling of the transition iron ions that may interfere with free‐radical formation, and is used clinically to treat conditions associated with iron overload. The effect of DFX on hepatic iron distribution has not been examined. Therefore, we have examined the effect of DFX on iron content and distribution, lipid peroxidation and DNA single‐strand breaks in liver. Since 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) enhances hepatic lipid peroxidation and induces DNA damage, the ability of DFX to modulate these effects was also examined. Female Sprague‐Dawley rats received 200 mg DFX kg−1 i.p. every 12 h for 10 days and 50 μg TCDD kg−1 p.o. on Day 4 as a single dose. All animals were killed 7 days after TCDD administration. The results demonstrate that DFX alone did not decrease hepatic iron content, but enhanced the iron distribution in mitochondria, microsomes and nuclei. A 10‐day administration of DFX resulted in enhanced hepatic lipid peroxidation and DNA single‐strand breaks, consistent with the alterations in iron distribution. TCDD administration produced large increases in lipid peroxidation in microsomes, nuclei and whole‐liver homogenates, as well as enhanced DNA damage. However, the marked increases in lipid peroxidation produced by TCDD were attenuated by DFX, while the DNA damaging effects of TCDD and DFX were additive. The results clearly demonstrate that a 10‐day administration of DFX does not result in hepatic iron depletion and the DFX‐associated increases in hepatic lipid peroxidation and DNA single‐strand breaks may reflect altered iron distribution or the formation of an iron‐catalysed nitroxide free‐radical of DFX.
The design of an experiment using statistical power with a startlechamber study as an example
Authors: Bittman Richard M. , Carniello Michael L. 
Published: October 2006

AbstractUsing a startle chamber experiment as a case study, it is shown how the sensitivity of a study's design can be quantified by using the concept of statistical power and how the design can be planned to achieve the power desired.The purpose of the experiment was to compare background responses in three empty startle chambers. The study design nested groups of noise events into trials, entailing two sources of experimental error, variation within trials and between trials. For this nested design, the proper statistical analysis and calculation of power are described. It is shown how the power depends on the numbers of trials and events per trial (sampling effort), magnitudes of the sources of variability and background differences to be detected. A worked example shows the power associated with several sampling alternatives. Associated implications for cost and benefit are also discussed.
Effects of 1,4‐naphthoquinone derivatives on red blood cell metabolism
Authors: Kruger‐Zeitzer Ellen , Sullivan Stephen Gene , Stern Arnold , Munday Rex 
Published: October 2006

AbstractThe effect on red blood cell metabolism of a series of substituted 1,4‐naphthoquinones has been investigated. 2‐Methoxy‐1,4‐naphthoquinone was found to be a potent oxidative compound, generating hydrogen peroxide in erythrocytes and causing both methemoglobin formation and glutathione depletion in the absence of glucose. Flux of glucose through both glycolysis and the hexose monophosphate shunt was stimulated, 2‐Hydroxy‐ and 2,3‐dihydroxy‐1,4‐naphthoquinone were less oxidative. Both compounds caused oxidation of glutathione and formation of hydrogen peroxide with corresponding stimulation of the hexose monophosphate shunt, but did not cause methemoglobin formation, 2‐Hydroxy‐3‐alkyl‐1,4‐naphthoquinones were not oxidative but did increase the flux of glucose through glycolysis, possiMy reflecting membranal damage. The in vitro oxidative effects of these substances do not correlate with their hemolytic activity in rats, indicating that factors other than oxidative damage are important in mediating the in vivo toxicity of these substances.
Acute toxicity induced by 2‐aryl‐N‐methylsuccinimides
Authors: Rankin Gary O. , Shih Hsien‐Cheng , Teets Vonda J. , Nicoll Derek W. , Brown Patrick I. 
Published: October 2006

AbstractPhensuximide (PSX) is a 2‐arylsuccinimide useful in the treatment of absence seizures. PSX is a mild urotoxicant and is structurally related to N‐phenylsuccinimide (NPS) and its antifungal derivatives. Since substitution of the phenyl ring of NPS with chloro or tert‐butyl groups can produce compounds with enhanced nephrotoxic potential, it was felt that similar substitutions on the phenyl ring of PSX also might produce derivatives with enhanced nephrotoxic potential. Three derivatives of PSX were prepared and tested: 2‐(3‐chlorophenyl)‐N‐methylsuccinimide (CPMS); 2‐(4‐tert‐butylphenyl)‐N‐methylsuccinimide (BPMS) and 2‐(3,5‐dichlorophenyl)‐N‐methylsuccinimide (DPMS). In one set of experiments, male Fischer 344 rats were administered a single intraperitoneal (i.p.) injection of a succinimide (0.4 or 1.0 mmol kg−1) or vehicle (sesame oil, 2.5 ml kg−1) and renal function monitored at 24 and 48 h. Only minor changes in renal function were noted with the PSX derivatives. BPMS and DPMS (1.0 mmol kg−1) treatment induced mild renal tubular necrosis and thickening of the glomerular membranes. However, no significant morphological changes were noted in ureters, bladder or liver in any treatment group. In a second set of experiments, rats were pretreated with phenobarbital (75 mg kg−1 day−1, i.p., 3 days) followed by a single i.p. injection of DPMS (0.4 or 1.0 mmol kg−1) or DPMS vehicle. Renal function was monitored as before. Phenobarbital pretreatment did not markedly enhance the functional nephrotoxicity induced by DPMS (0.4 mmol), but tubular necrosis was greater than observed in non‐phenobarbital‐pretreated rats receiving DPMS (1.0 mmol kg−1). In addition, hepatotoxicity was observed as the appearance of numerous non‐staining vacuoles in hypertrophied hepatocytes. In the phenobarbital plus DPMS (1.0 mmol kg−1) treatment group, all rats died by 48 h. Prior to death, rats exhibited increased proteinuria (+3), hematuria (+3) and blood urea nitrogen concentration. At 24 h, kidneys from rats treated with phenobarbital plus DPMS (1.0 mmol kg−1) exhibited extensive proximal tubular necrosis and numerous glomeruli with thickened membranes. Hepatotoxicity was more pronounced than with phenobarbital plus DPMS (0.4 mmol kg−1) at 48 h and urinary bladders had focal areas of erythrocytes pooling below the epithelial lining. These results demonstrate that although NPS and PSX are structural analogs, chemical substitutions that enhance the nephrotoxic potential of NPS do not have a similar effect on PSX. In addition, DPMS can induce urotoxicity in a manner similar to that observed for PSX and probably induces toxicity via one or more metabolites.
Mutagenicity and genotoxicity of ethylvinyl ketone in bacterial tests
Authors: Deininger Christoph , Eder Erwin , Neudecker Tilmann , Hoffman Christian 
Published: October 2006

AbstractThe mutagenic and genotoxic effects of ethylvinyl ketone were investigated. This α, β‐unsaturated carbonyl compound is widely distributed in the environment, in particular in food. Whereas ethylvinyl ketone shows only weak genotoxicity in the SOS Chromotest with Escherichia coli PQ37, it was distinctly mutagenic per se in the Salmonella preincubation assay with TA100. Using SKF 525 (an inhibitor of microsomal monooxygenase) and trichloropropene oxide (an inhibitor of epoxide hydrolase) we found indication for additional activation via epoxidation by S9 mix. The need for further investigation of the genotoxic, mutagenic and carcinogenic effects of this compound is strongly indicated.
Effects of in ovo injection of carbamates on chick embryo hatchability, esterase enzyme activity and locomotion of chicks
Authors: Farage‐Elawar Miranda 
Published: October 2006

AbstractCarbaryl and aldicarb, two carbamate pesticides used extensively throughout the United States, are known to act as acetylcholinesterase inhibitors. We have demonstrated previously that exposure to carbaryl and aldicarb in young chicks caused persistent locomotion alterations with no correlation to esterase inhibition. In this study, we investigated the effects of these carbamates when injected in ovo to chick embryos, at two time periods (days 5 and 15) during incubation. Carbaryl dosed at 45 mg kg−1 egg weight was extremely toxic to the embryos on day 5 of incubation. Hatchability was reduced to 0% as compared to 80% when carbaryl was injected on day 15 of incubation. Aldicarb at 1.5 mg kg−1 egg weight had no major effect on hatchability when injected either on day 5 or day 15 of incubation (hatchability = 90 and 100%, respectively). Plasma, liver and brain esterases were measured in the chick at different time points during incubation and after hatching. Brain acetylcholinesterase (AChE) and liver cholinesterase (ChE) were inhibited significantly during incubation in embryos dosed on day 15 with both carbaryl and aldicarb. Liver carboxylesterase was inhibited significantly during incubation with only the carbaryl treatment. All esterase enzyme activities returned to normal after hatching. Plasma ChE and carboxylesterase levels were not affected with either carbaryl or aldicarb treatment from 8 until 47 days after hatching. Neither carbamate had any effect on brain neuropathy target esterase (NTE) activity either during incubation or after hatching. The locomotion of chicks was affected in both treatment groups until 47 days after hatching. This study indicates that carbaryl and aldicarb may cause long‐term delayed alterations in the chicks.
Acute effects of the antiepileptic succinimides on the urinary tract and potentiation of phensuximide‐induced urotoxicity by phenobarbital
Authors: Rankin Gary O. , Teets Vonda J. , Nicoll Derek W. , Brown P. I. 
Published: October 2006

AbstractPhensuximide (PSX), methsuximide (MSX) and ethosuximide (ESX) are succinimide antiepileptic agents used worldwide in the treatment of absence seizures. A previous study from our laboratory demonstrated that PSX (0.3 or 0.6 mmol kg−1 day−1, i.p.) induced urotoxicity following daily administration for 5–7 days in Fischer 344 rats, but PSX (1.25 mmol kg−1, i.p.) induced only minimal urotoxicity following acute administration. The purpose of this study was to determine the acute nephrotoxic potential of MSX and ESX in male Fischer 344 rats and if antiepileptic succinimide‐induced urotoxicity is potentiated by phenobarbital pretreatment. In one set of experiments, rats (four rats per group) were administered a single intraperitoneal (i.p.) injection of a succinimide (0.4 or 1.0 mmol kg−1) or vehicle (sesame oil, 2.5 ml kg−1), and the renal function was monitored at 24 and 48 h. Neither ESX or MSX induced substantial changes in renal function or morphology, which suggests that neither compound is acutely nephrotoxic. Similar results were obtained with PSX, which supported our earlier findings with this antiepileptic agent. In a second set of experiments, rats (four rats per group) were pretreated for 3 days with phenobarbital (75 mg kg−1 day−1, i.p.) prior to receiving a succinimide (0.4 or 1.0 mmol kg−1, i.p.) or vehicle (sesame oil, 2.5 ml kg−1, i.p.). Renal function was monitored at 24 and 48 h after the last injection. Phenobarbital pretreatment had only minor effects on ESX‐ or MSX‐induced renal effects, with no significant morphological changes detected between treated and pair‐fed control groups. However, PSX‐induced urotoxicity was potentiated by phenobarbital. Marked hematuria and proteinuria were observed following PSX (1.0 mmol kg−1) administration to phenobarbital‐pretreated rats. Bladders from these animals contained bloody urine and exhibited hemorrhagic areas among the bladder epithelial cells. Proximal tubular cells exhibited mild damage, with some swelling and blebbing at the brush border membrane. These results suggest that phenobarbital potentiates PSX‐induced urotoxicity and that the resulting hemorrhagic cystitis is mediated by one or more PSX metabolites.