bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of renal function and damage in animal species. A review of the current approach of the academic, governmental and industrial institutions represented by the animal clinical chemistry association
Authors: Stonard M. D. 
Published: October 2006

AbstractThere are a wide variety of laboratory tests available to assess damage to and functional impairment of the kidneys, although the effectiveness of these tests varies greatly depending upon the site specificity of the damage and to a lesser extent upon the animal species involved.Several traditional tests of renal dysfunction and damage, including plasma creatinine and urea, and urinalysis (dipstick and/or quantitative protein), can be used in the first instance to detect nephrotoxicity. A second tier of specific, targetted indicators (concentration test, urinary enzymes, clearance of analytes, specific proteins, etc.) may then be applied to identify further the site of the lesion and the functional status of the kidneys.The glomerular filtration rate (GFR) may be estimated from the clearance of exogenous and endogenous substances. The difficulty in obtaining accurately timed urine samples limits the value of these tests in small animals, although methods that do not involve urine collection are available.The kidney is the origin of several enzymes found in urine that can be used to monitor the toxic effects of chemicals and therapeutic substances. Selective measurement of enzyme activities in urine can be used to detect the site of the renal lesion after traditional tests have established the presence of renal injury. Separation of proteins in urine by electrophoretic techniques may also be used to discriminate damage to different parts of the nephron.Renal cell excretion in urine is a sensitive but unreliable indicator of acute damage to the proximal tubule. The rate of cell excretion is not a good predictor of the severity of tubular injury.The tests available, and their use in toxicological investigations, have been reviewed in the light of current practice in the UK.
The role of membrane composition in ATPase activities of cirrhotic rat liver: Effect of silymarin
Authors: Muriel Pablo , Mourelle Marisabel 
Published: October 2006

AbstractThe activities of Ca2+‐ and Na+, K+ ‐ATPases were studied in liver plasma membranes from CCI4‐cirrhotic rats and from livers of rats treated with silymarin in addition to CCI4. CCI4 chronic treatment produced significant decreases in Na+, K+‐ and Ca2+‐AT Pase activities; however, the animals treated with silymarin along with CCI4 showed no differences in ATPase activities as compared to controls. The lipid analysis performed in plasma membranes revealed increases in the cholesterol/phospholipid (CH/PL) and sphingomyelin/phosphatidylcholine (SM/PC) ratios in the cirrhotic group. Again, the membranes isolated from rats receiving CCI4 + silymarin showed normal CH/PL and SM/PC values. Considering that CH/PL and SM/PC ratios are related to membrane microviscosity, this study suggests that a lower fluidity of the membrane may be responsible for the observed decreases in ATPase activities in the cirrhotic group. Additionally, the role of silymarin to improve liver function in CCI4‐cirrhosis can be attributed partially to its action at membrane level by preventing the increases in CH/PL and SM/PC ratios.
Role of glutathione in vanadate reduction in young and mature rats: Evidence for direct participation of glutathione in vanadate inactivation
Authors: Kretzschmar M. , Bräunlich H. 
Published: October 2006

AbstractThe influence of renal glutathione content, modulated by the glutathione synthesis inhibitor buthionine sulphoximine or by glutathione infusion, on the polyuric and natriuretic effects of i.v. administered vanadate was investigated in 20‐ and 5‐day‐old rats. The modulation of renal glutathione content led to significant changes in urine volume and sodium excretion, independently of age.A decrease in the renal glutathione level led to intensification and prolongation of the diuretic effects of vanadate in 55‐day‐old animals. Treatment with glutathione abolished and treatment with buthionine sulphoximine increased the polyuric effect of vanadate. These observations indicate a role for renal glutathione in vanadate inactivation. Age‐dependent differences in the polyuric and natriuretic effectiveness of vanadate are caused by differences in renal glutathione content during maturation of the kidney.
The role of iron in t‐butyl hydroperoxide‐induced lipid peroxidation and hepatotoxicity in rats
Authors: Younes Maged , Wess Alexander 
Published: October 2006

AbstractTreatment of rats with 100 mg kg−1 t‐butyl hydroperoxide led to an enhanced ethane exhalation as a marker of in vivo lipid peroxidation, as well as a moderate hepatoxicity as evidenced by a rise in plasma activities of liver‐specific enzymes (glutamate‐pyruvate transaminase and sorbitol dehydrogenase) and an increase in hepatic calcium content. Furthermore, a depletion of hepatic glutathione by 17% was observed. Apart from the loss of glutathione, all these effects were antagonized by pretreatment of rats with the potent iron chelator deferrioxamine and potentiated by pretreatment with low concentrations of FeSO4 having no pro‐oxidant activity per se; this was also the case in rats under conditions of iron overload (experimental haemochromatosis). These data indicate a close relationship between t‐butyl hydroperoxide‐induced lipid peroxidation and its hepatotoxicity, and point out the importance of iron in catalysing reinitiation (propagation) reactions of lipid peroxidation in vivo.
Embryotoxicity and teratogenicity study in rats dosed epicutaneously with dimethylformamide (DMF)
Authors: Hansen Ernst , Meyer Otto 
Published: October 2006

AbstractThe reproductive effect of N,N‐dimethylformamide (DMF) administered epicutaneously to rats was examined. The rats were dosed on gestation days 6–15 or on gestation days 1–20 at dose levels of up to 2 ml DMF kg−1 body weight. Body weight, weight gain and pregnancy rate were reduced in those rats receiving 2 ml DMF kg−1 body weight per day on days 6–15. A reduction in the number of live fetuses and in fetal weight, as well as an increase in postimplantation loss, were also observed at this dose level. Similar but more pronounced effects were observed in rats dosed on days 1–20 with 2 ml DMF kg−1 body weight. The lowest effect level was 1 ml DMF kg−1 body weight. No other dose‐related effects were found in this study.
Evaluation of the teratogenic potential of the plasticizer butyl benzyl phthalate in rats
Authors: Ema Makoto , Murai Toshimi , Itami Takafumi , Kawasaki Hironoshin 
Published: October 2006

AbstractThe teratogenicity of butyl benzyl phthalate (BBP) was studied in Wistar rats. Pregnant rats were given BBP at a dosage of 0, 0.25, 0.5, 1.0 or 2.0% in the diet from day 0 to day 20 of pregnancy. Daily intakes of BBP were 185 mg kg−1 for the 0.25% group, 375 mg kg−1 for the 0.5% group, 654 mg kg−1 for the 1.0% group and 974 mg kg−1 for the 2.0% group. Adjusted maternal body weight gain (body weight gain excluding the gravid uterus) during pregnancy in the 1.0 and 2.0% groups was significantly lowered. Food consumption during pregnancy in the 0.25 and 0.5% groups did not differ from that in the control group. No death was noted in the pregnant females of any group. There was no significant compóund‐related effects on the incidence of prcimplantation loss. All dams given 2.0% BBP exhibited complete resorption of all the implanted embryos. Morphological examinations of the fetuses revealed no evidence of teratogenesis. It could be concluded that the no‐observable‐effect‐levels (NOEL) in rats were 0.5 and 1.0% BBP in the diet for maternal and embryofetal toxicity, respectively.
No evidence of toxicity or carcinogenicity of pentaerythritol tetranitrate given in the diet to F344 rats and B6C3F1 mice for up to two years
Authors: Bucher John R. , Huff James , Haseman Joseph K. , Eustis Scot L. , Lilja Herman S. , Murthy A. S. K. 
Published: October 2006

AbstractToxicology and carcinogenesis studies of pentaerythritol tetranitrate (PETN), an organic nitrate used in explosives and as a therapeutic agent for angina pectoris, were conducted by administering diets containing PETN,NF (National Formulary Grade, a 1:4 mixture of PETN and lactose) to both sexes of F344 rats and B6C3F1 mice in 14‐day, 13‐week and 2‐year studies. PETN was found to be essentially non‐toxic in 14‐day and 13‐week studies at dietary concentrations as high as 10 000 ppm; the weight gain of female rats was lower than that of controls at 5000 and 10 000 ppm in the 13‐week study. In the 13‐week studies, one in ten high‐dose female rats had an adenoma of the Zymbal gland and one in ten high‐dose female mice had a hepatocellular adenoma. Dietary concentrations chosen forthe 2‐year studies were 5000 and 10 000 ppm for male rats and male and female mice, and 1240 and 2500 ppm for female rats. Inthe 2‐year studies, there were no adverse effects on survival or body weight gains in either sex of rats or mice. No neoplastic or non‐neoplastic lesions were considered to be related clearly to PETN administration. Neoplasms of the Zymbal gland occurred at low incidences in PETN‐exposed groups of both sexes of rats inthe 2‐year study.
Effect of calcium channel blocking agents on the reductive metabolism of halothane
Authors: Kawahara Michio , Akita Susumu , Fujii Kohyu , Morio Michio 
Published: October 2006

AbstractThe effect of calcium channel blocking agents on the reductive metabolism of halothane in liver microsomes of guinea pigs was investigated. The reaction mixture for the measurement of the end products consisted of microsomal suspension, 5 mM NADPH, calcium channel blocking agents (verapamil, diltiazem, nicardipine and nifedipine) and halothane in 0.1 M phosphate buffer (pH 7.4). The reductive metabolism of halothane was inhibited competitively by verapamil, diltiazem and nicardipine. The binding spectra for the interaction of these three drugs with cytochrome P‐450 in microsomes were investigated. Verapamil caused the reverse type I difference spectrum and diltiazem caused the type I difference spectrum. However, the change caused by nicardipine was not observed by the presence of its specific spectra. NADPH–cytochrome P‐450 reductase activity in microsomes did not change by the addition of these three drugs. These results suggest that these three calcium channel blocking agents inhibit the production of radical intermediates during the reductive metabolism of halothane.
A comparison between the isovolume and the end‐inflation occlusion methods for measurement of lung mechanics in rats
Authors: Cardoso Wellington Veras , Saldiva Paulo Hilário Nascimento , Martins Patricia , Criado Pereira , Sakae Regina Silvia , Böhm György Miklós , Zin Walter Araújo 
Published: October 2006

AbstractThe isovolume method is one of the most used techniques to assess the mechanical properties of the lungs in ordinary challenge tests and in toxicological studies. It has been considered that isovolume lung resistance (RL) could assess central airway calibre in such tests, whereas dynamic elastance (EL,dyn) would reflect the elastic properties of lung parenchyma. However, peripheral phenomena, such as Pendelluft and stress relaxation, can interfere with RL measurements, especially in disease. In order to investigate the contribution of such phenomena to isovolume RL and EL,dyn, we compared the results provided by isovolume technique with those given by the end‐inflation occlusion method (EIOM) in 12 normal Wistar rats. We found similar values for total lung resistance (RL,max) and isovolume RL. Homogeneous resistance (RL,min), which describes airway calibre, comprised about 30% of RL in the tidal volume range. Values of EL,dyn calculated by the EIOM were approximately 20% greater than the corresponding value measured during spontaneous breathing. Our data indicate that isovolume RL is significantly affected by tissue forces and cannot be interpreted as a pure index of airway size.
Haemolytic activity and nephrotoxicity of 2‐hydroxy‐1,4‐naphthoquinone in rats
Authors: Munday R. , Smith B. L. , Fowke E. A. 
Published: October 2006

AbstractThe short‐term toxicity of 2‐hydroxy‐1,4‐naphthoquinone (lawsone) and 2‐methyl‐1,4‐naphthoquinone (menadione) has been compared in rats.2‐Methyl‐1,4‐naphthoquinone has been shown previously to cause haemolytic anaemia in animals, and this was confirmed in the present experiment. 2‐Hydroxy‐1,4‐naphthoquinone was found also to cause haemolysis, in a dose‐dependent manner, as reflected by decreased blood packed cell volumes and haemoglobin levels and by histopathological changes in spleen, liver and kidney. With both naphthoquinones, the haemolysis was of the oxidative type, characterized by the presence of Heinz bodies within erythrocytes.Haemolysis was the only toxic change identified in rats dosed with 2‐methyl‐1,4‐naphthoquinone. In contrast, 2‐hydroxy‐1,4‐naphthoquinone was not only a haemolytic agent but also a nephrotoxin, causing renal enlargement, elevated plasma levels of urea and creatinine and histologically‐identified tubular necrosis, largely confined to the distal segment of the proximal convoluted tubules.The relationship between the in vivo toxic effects of these naphthoquinones and previously‐reported data on their in vitro cytotoxic action is discussed.
Gene mutation assay of acrolein in the CHO/HGPRT test system
Authors: Parent Richard A. , Caravello Halina E. , Harbell John W. 
Published: October 2006

AbstractThe mutagenic potential of acrolein has been studied with a wide range of in vitro and in vivo genetic toxicity assays. The data often have been conflicting, especially with the Ames assay. This study was undertaken to assess the mutagenic potential of acrolein using the CHO/HGPRT assay, both with and without metabolic activation. This assay system was chosen because it provides eukaryotic DNA as the target and is capable of detecting a range of mutational events. Because of its considerable toxicity, acrolein was tested over a very narrow dose range of 0.2–2 nl ml−1 without exogenous activation and 0.5–8 nl ml−1 with rat S‐9 activation. Multiple assays were performed under both conditions. The results indicated that while acrolein was clearly very cytotoxic, it did not induce a significant mutagenic response in the presence or absence of metabolic activation.
Globin adducts of benzo[a]pyrene: Markers of inhalation exposure as measured in F344/N rats
Authors: Bechtold W. E. , Sun J. D. , Wolff R. K. , Griffith W. C. , Kilmer J. W. , Bond J. A. 
Published: October 2006

AbstractWe have explored methods for determing benzo[a]pyrene (BaP) dosimetry by measuring adduction levels to F344/N rat blood hemoglobin, and have refined and validated an assay that measures the in vivo binding of the 7, 8‐diol 9, 10‐epoxide metabolite of BaP to globin. The assay for BaP‐globin adducts was based on the release of tetrahydroxy‐BaP (BaP‐tetrols) from globin by mild acid hydrolysis. After extensive isolation, BaP‐tetrols were quantitated by high‐pressure liquid chromatography using fluorescence detection. BaP‐tetrol levels were measured in rats dosed intraperitoneally with 242, 71 and 24 μmol BaP kg−1 body weight in corn oil. The formation of BaP‐tetrols was not linear with dose. The lowest dose yielded adduct levels that represented the limits of sensitivity for the method, as performed in this laboratory. Once this limit of sensitivity was established, the potential use of the assay was assessed by measuring the radiochemical binding of inhaled [14C]BaP or its metabolites to the globin of F344/N rats. Rats were exposed for 4 h per day, 1 day per week, for 12 weeks to pure aerosols of [14C]BaP at a level of 2 mg m−3. At the conclusion of exposure, rats were sacrificed and globin was isolated. The extent of [14C]BaP binding to the globin was determined by liquid scintillation spectrometry. Rats exposed to aerosols of [14C]BaP had statistically increased levels of binding to globin, and the levels were comparable to those observed previously after intragastric administration. Based on the spectroscopic assay data, the sensitivity of the proposed analytical method was projected to be insufficient to measure BaP‐tetrol levels after inhalation exposures similar to those described above. The use of the globin‐BaP adduct approach may be limited by the small fraction of BaP‐tetrols that can be released by acid hydrolysis.
A CCl4/CHCl3 interaction study in isolated hepatocytes: Non‐induced and phenobarbitalpretreated cells
Authors: O'Hara Todd M. , Sheppard Melissa A. , Clarke Elizabeth C. , Borzelleca Joseph F. , Gennings Chris , Condie Lyman W. 
Published: October 2006

AbstractThe purpose of this study was to evaluate an isolated hepatocyte model for predicting the in vivo hepatotoxicity of carbon tetrachloride (CCl4) and chloroform (CHCl3), alone and in combination. Response surface methodology (RSM) was used to analyze and describe the data. The interaction was evaluated for % initial K+ (cell injury) and % LDH leakage (cell death) in non‐induced (untreated) and phenobarbital‐pretreated suspended hepatocytes. CCl4 and CHCl3 were delivered alone and in combination in dimethyl sulfoxide (DMSO) to suspended hepatocytes. The maximum observed no‐effect level (MONEL) for CCl4 in non‐induced cells was 1.0 mM (LDH and K+). In induced cells, the MONEL was 0.25 mM (K+) and 0.5 mM (LDH). The MONEL for CHCl3 in non‐induced cells was 5.0 mM (LDH and K+) and in induced cells was 0.5 mM (K+) and 1.0 mM (LDH). Phenobarbital pretreatment enhanced the toxicity of both CCl4 and CHCl3, alone and in combination. RSM analysis of the % initial K+ and % LDH for CCl4 and CHCl3 in combination in non‐induced and induced cells showed a greater than additive interaction. The isolated hepatocyte model appears to be a promising system for evaluating the toxicity of chemical mixtures and predicting their in vivo effects.
Chinese hamster ovary cell assays for mutation and chromosome damage: Data from non‐carcinogens
Authors: Oshiro Y. , Piper C. E. , Balwierz P. S. , Soelter S. G. 
Published: October 2006

AbstractIn vitro genotoxicity tests are employed to screen chemicals for their capability to cause various DNA and chromosomal alterations, and the results are often used to predict their potential for carcinogenicity. However, there is controversy regarding the apparent low specificity of some in vitro genotoxicity assays, which result in a high false positive rate. Since we use and rely upon in vitro assays for risk assessment and prediction of carcinogenicity, this specificity issue is of serious concern to us. Hence, we selected ten compounds deemed non‐carcinogens in the literature to test for the induction of gene mutation and chromosomal damage using the Chinese hamster ovary cell/hypoxanthine–guanine phosphoribosyl transferase (CHO/HGPRT) mutation assay performed concurrently with a CHO micronucleus assay. The chemical exposures for the two end‐points were done simultaneously. The protocol for the two end‐points was developed using the carcinogens N‐methyl‐N'‐nitro‐N‐nitrosoguanidine, 3‐methylcholanthrene, cyclophosphamide and 7, 12‐dimethylbenzanthracene. The non‐carcinogens chosen were 4‐nitro‐o‐phenylenediamine, p‐phenylenediamine dihydrochloride, 3‐nitropropionic acid, dichlorvos, 2‐(chloromethyl)pyridine, N‐(1‐naphthyl)ethylenediamine 2HCl, O‐anthranilic acid, 4‐nitroanthraniic acid, anilazine and triphenyltin hydroxide. Each of these chemicals had been reported positive in the Ames test and/or the mouse lymphoma TK+/‐ mutation assay. In addition, eight of them were also reported positive in in vitro assays for chromosome aberrations and/or sister chromatid exchange (SCE). We found four of the ten chemicals negative for gene mutation and micronucleus induction without and with activation in the CHO/HGPRT mutation and CHO micronucleus assays. However, one of these four chemicals may be a potential carcinogen according to other carcinogenicity reviewers. Four other chemicals that induced only micronuclei were negative for gene mutation. Dichlorvos was positive for gene mutation and micronucleus induction without and with activation. This chemical has been shown recently to cause various tumors in rodents. One of the non‐carcinogens was positive in the micronucleus test and equivocally positive in the mutation test. These results indicate that the CHO/HGPRT mutation assay may provide more relevant results than the CHO micronucleus assay, the mouse lymphoma mutation assay, or in vitro SCE and chromosome aberration assays when screening chemicals for potential carcinogenicity.
Site of action of grayanotoxins in mad honey in rats
Authors: Onat Filiz , Yegen Berrak C. , Lawrence Roger , Oktay Ahmet , Oktay Sule 
Published: October 2006

AbstractGrayanotoxins are known to occur in honey produced from the nectar of Rhododendrons of the family Ericaceae. Grayanotoxins extracted from honey sample obtained from a patient who experienced severe bradycardia and hypotension after ingesting two tablespoonfuls corresponded to Rhododendron ponticum tetrades. Anaesthetized albino rats were injected with honey extract intracerebroventricularly or intraperitoneally. The intracerebroventricular dose was equivalent to 50 mg honey and i.p. doses were equivalent to 50 mg, 1 mg kg−1 and 5 g kg−1 honey. Marked bradycardia and respiratory rate depression were observed in rats injected with extract equivalent to 1 and 5 g kg−1 honey i.p. and in rats injected with 50 mg i.c.v., but not in rats given 50 mg i.p. In bilaterally vagotomized animals, grayanotoxin‐contaminated honey extract was not bradycardic. These results suggest that the sites of cardiac and respiratory actions are within the central nervous system, and that the bradycardic effect of grayanotoxin is mediated by vagal stimulation at the periphery.
Biochemical toxicology of argemone oil. I. effect on hepatic cytochrome P‐450 and xenobiotic metabolizing enzymes
Authors: Upreti Kaushal K. , Das Mukul , Khanna Subhash K. 
Published: October 2006

AbstractThe in vivo effect of argemone oil on hepatic xenobiotic metabolizing enzymes was investigated in albino rats following either a single (10 ml kg−1 body wt.) or multiple intraparenteral doses (5 ml kg−1 body wt.) for three days. Animals sacrificed 72 h after a single intraparenteral dose of argemone oil exhibited a significant loss of hepatic cytochrome P‐450 (35%) and cytochrome bs (34%) contents and inhibition of aminopyrine‐N‐demethylase (APD), aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin‐O‐deethylase (ECD) activities (21–39%). Three successive 24‐hourly intraparenteral injections of argemone oil followed by sacrificing the animals after 24 h of the last injection, showed a greater degree of inhibition of the content of cytochrome P‐450 (58%) and its dependent mixed‐function oxidases (35–63%). Also, multiple treatment of argemone oil caused a depletion of endogenous hepatic glutathione (GSH) content (72%) with a concomitant increase in lipid peroxidation (177%) and decrease in glutathione‐S‐transferase (GST) activity (30%). A significant decrease in relative liver weight (39%) was observed in animals treated with multiple treatment of argemone oil. These results suggest that argemone oil can alter both membrane and cytosolic defences and destabilizes the hepatic cytochrome P‐450 dependent mixed‐function oxidase system, so that it tips in the direction of autooxidative peroxidation of lipids.