摘要:

AbstractThe effect of acute exposure to lead acetate (LA)/lead nitrate (LN) on onset and severity of convulsions induced by a low dose of picrotoxin was examined in rats. Both LA and LN reduced the time of onset and exacerbated the severity of convulsions, with a resultant high lethality. On comparison, it was noted that in the LA‐pretreated group, convulsion scores and incidence of tonus and mortality were much higher; the appearance of tonus was more delayed than in the LN‐pretreated group. In lead‐pretreated animals, the potentiation of picrotoxin‐induced convulsions was accompanied by higher lead levels in blood (p<0.001). However, the whole‐brain lead levels were not significantly different in these animals compared to the controls. The difference in the degree of potentiation by the two forms of lead could possibly be attributed either to the role of a combination of anions and cations or to the variable cerebral uptake and regional distribution of lead or due partly to the extent of competitive interaction involvingd‐aminolaevulinic acid—whose level is known to be elevated consequent to lead‐induced disruption of haem biosynthesis–

ISSN:0260-437X    

DOI:10.1002/jat.2550130303

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractEarly cytotoxic events were studied on B77 fibroblasts. Cells were treated with sulphur mustard (SM) in short‐term experiments in which cell viability was unchanged, as evaluated by the neutral red cytotoxicity test. This treatment was correlated to two early signs of cytotoxicity. The intracellular Ca2+concentration [Ca2+]ilevel in SM‐treated Fura‐2‐loaded fibroblasts showed a significant dose‐dependent increase. This observed rise was sustained, in contrast to the Ca2+signal induced by serum, and was already visible 5–10 min after the addition of SM to cell suspensionsin vitro. Modification of the extracellular Ca2+concentration in the medium had no effect on the cytosolic calcium rise caused by SM, suggesting release from intracellular Ca2+pools. Furthermore, a time‐dependent inhibition of the [Ca2+]itransient increase induced by growthfactors (as evaluated by the fetal calf serum (FCS) response) was observed within the first hour of exposure. These latter results suggest that early alterations of calcium distribution induced by SM could be one of the earliest markers of SM

ISSN:0260-437X    

DOI:10.1002/jat.2550130304

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractA re‐examination of data presented by Dastonet al.provided an opportunity to assess the occurrence of chemical hormesis due to the wide dosage range tested and to the large number of treatments within the dosage range. The data revealed numerous examples of possible chemical hormesis for a variety of end‐points measu

ISSN:0260-437X    

DOI:10.1002/jat.2550130305

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractA review of the literature was conducted to provide an overview of organophosphorus (OP)‐induced morphological changes in the non‐human primate. Most studies have evaluated effects of the OP nerve agent soman (pinacolyl methylphosphonofluoridate), an irreversible inhibitor of acetylcholinesterase. Soman‐induced acute and chronic morphological changes have been examined. The effects of nerve agent therapy (i.e. pyridostigmine, praloxidime chloride and atropine), with and without an anticonvulsant (i.e. diazepam, midazolam), on soman‐induced lesions have also been studied. Acute changes in the central nervous system of rhesus and cynomolgus monkeys exposed to soman alone or soman and therapy, without an anticonvulsant, were characterized by neuronal degeneration and necrosis and neuropil edema. The lesions were usually present in the frontal cortex, entorhinal cortex, amygdaloid complex, caudate nucleus, thalamus and hippocampus. Morphologically, these lesions resemble lesions produced by hypoxic‐ischemic injury or by seizures and are similar to soman‐induced changes in other laboratory animals. Nerve agent therapy supplemented with an anticonvulsant reduced or prevented soman‐induced acute neural lesions. Acute changes in non‐neural tissues were limited to the heart (e.g. hemorrhage, myofiber necrosis, myocarditis) and skeletal muscle (e.g. myofiber necrosis). Heart lesions in the non‐human primate are similar to OP‐induced heart lesions in man. The pathogenesis of the acute lesions in both the central nervous system and heart is discussed. Consistent soman‐induced chronic morphological changes have not been produced in the rh

ISSN:0260-437X    

DOI:10.1002/jat.2550130306

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractTransmethylation is an important means of altering the biological activity of a wide variety of compounds. In human and experimental CCI4‐liver cirrhosis the intrahepatic content ofS‐adenosyl‐L‐methionine (SAM), an active methyl donor, and the SAM‐transmethylase activity are markedly reduced. Previously, it has been reported that SAM administration preserves hepatocyte plasma membrane Na+/K+‐ATPase and Ca2+‐ATPase activities in cirrhotic rats. Therefore, the aim of this work was to study the effect of SAM administration on the membrane lipid composition and the ATPase activity on erythrocytes derived from CCI4‐cirrhotic rats. Male Wistar rats were used in these experiments. In group 1, cirrhosis was induced by i.p. administration of CCI4. Animals of group 2 received, in addition to CCI4, three daily doses of SAM (20 mg kg−1, i.m.). Group 3 consisted of cirrhotic animals that, after 8 weeks of CCI4treatment, received SAM (20 mg kg−1, i.m., three times daily) for 4 weeks without discontinuation of CCI4. Group 4 included animals treated with SAM alone. Seventy‐two hours after the end of treatment the rats were anaesthetized, blood was collected by heart puncture and the erythrocyte plasma membranes were isolated. The Na+/K+‐and (Ca2++ Mg2+)‐ATPase activities and the cholesterol (CH) and phospholipid (PL) contents were determined in the plasma membranes. The Na+/K+‐ and Ca2+‐ATPase activities were both significantly decreased (twofold) in the CCI4‐treated group as compared to controls. Administration of SAM completely prevented this fall in both ATPases. In group 4, the Na+/K+‐ATPase activity was partially restored but the Ca2+‐ATPase activity was completely restored. CCI4increased the CH/PL ratio; however, this alteration was not observed in the group treated with CCI4+SAM simultaneously and was completely reversed in group 4. Since the increase in the membrane CH/PL ratio decreases the membrane fluidity and thus changes the enzyme activity, two mechanisms by which SAM preserves the ATPase activity in cirrhotic rats could be by preventing the increase in the CH/PL ratio

ISSN:0260-437X    

DOI:10.1002/jat.2550130307

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractToxicities of pesticidal mixtures in biological systems have not been explored adequately. Therefore, mixtures of ten widely used pesticides were evaluated for their toxicity in ICR male mice (21–24 g). Mice were given four mixtures of alachlor, aldrin, atrazine, 2,4‐dichlorophenoxyacetic acid, DDT, dieldrin, endosulfan, lindane, parathion and toxaphene, at 0.01, 0.1, 1.0 and 10 ppm of each of these pesticides, in drinking water for 90 daysad libitum.Also, two mixtures at 2.5 and 5 mg kg−1of each pesticide in 7.5% Tween‐80 in water were administered to additional groups of mice by oral intubation daily for up to 14 days. In relation to the control, the 90‐day exposure caused a dose‐dependent increase in the liver/body weight ratio (3–44%), a decrease in the pentobarbital (60 mg kg−1, i.p.)‐induced sleep time (11–79%) and an increase in the metabolism of aniline (233–399%), amidopyrine (79–231%), phenacetin (127–318%) and benzo[aIpyrene (286–1633%)] in the 9000ghepatic supernatants from the mixture‐treated mice. Proliferation, dilatation and fragmentation of the endoplasmic reticulum and scattering of ribosomes were noticed with mixture livers. In the 5 mg kg−1group, 90% of the animals died by Day 8; incidence of death was considerably less in the 2.5 mg kg−1group. The serum cholinesterase activity was inhibited by ca. 50% in the 2.5 and 5 mg kg−1groups on either one or both of Days 8 and 15; the liver/body weight ratio increased by 24–79% and the pentobarbital‐induced sleep time decreased by 80–96%. On Days 8 and 15, thein vitrohepatic metabolism of amidopyrine, phenacetin and benzo[a]pyrene in the 2.5 or 5 mg kg−1group was considerably increased (100–1478%). Findings from this study suggest that these mixtures have the potential to induce the xenobiotic‐metabolizing enzymes in liver; thus, exposures to the pesticidal mixtures might cause deleterious effects in other species, including hum

ISSN:0260-437X    

DOI:10.1002/jat.2550130308

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

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

ISSN:0260-437X    

DOI:10.1002/jat.2550130309

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractEight pregnant rats were exposed, on the 17th day of gestation, for 95 min to a microcondensation aerosol of benzo[a]pyrene at five different atmospheric concentrations between 200 and 800 mg m−3in a ‘head‐only’ inhalation chamber. Five rats were killed immediately following the exposure and three were killed at 6 h post‐dosing. Concentrations of the radiolabel and ‘free’ benzo[a]pyrene were measured in the individual fetuses and in the maternal blood, fat, kidney, liver and lung.Distribution to the fetus did not appear to be related to its position on the uterine horn and the uptake of benzo[a]pyrene was non‐linear with increasing exposure concentrations, which was similar to the observations previously reported for pyrene. The levels of benzo[a]pyrene were much higher in the fetus and, especially, the lung than those observed in the pyrene study; so also were the levels of total metabolites in these tissues, which might, in part, account for the carcinogenic potency of

ISSN:0260-437X    

DOI:10.1002/jat.2550130310

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractCadmium was given to female rats in the drinking water (50 ppm Cd) from 4 weeks before mating until weaning (a total of 10 weeks). Four weeks after the discontinuation of exposure, mothers and offspring were then given two i.p. doses of 1 mmol kg−1sodiumN‐(4‐methoxybenzyl)‐D‐glucamine‐N‐carbodithioate monohydrate (MeOBDCG) on subsequent days. Cadmium in kidneys and liver was determined in groups of mothers before mating and in mothers and pups after parturition, at the end of lactation and 4 and 5 weeks after the discontinuation of exposure. An additional measurement was made in pups in the middle of the lactation. period. Cadmium deposition rapidly increased in the two organs between the 11th and 21st day of lactation. At all times, Cd concentrations in the liver and kidneys of mothers were several orders higher than in the offspring. After the discontinuation of exposure, maternal hepatic and renal Cd contents showed a significant decrease. Treatment with the chelator depleted the hepatic Cd stores in mothers by 90% and in pups by 80%, while the corresponding renal depletions were only 23% and 12%, respectively. The liver and kidney contents of Cd (but not the concentration) increased by a higher factor during lactation than during pregnancy and exposure during lactation was also more important for pups than prenatal exposure.The lower efficiency of the chelator in the offspring indicates that Cd accumulated during the neonatal period was less accessible to treatment with chelating agents than Cd accumulated in later life. It is more likely that with increasing Cd concentration a smaller proportion of Cd is bound to strong

ISSN:0260-437X    

DOI:10.1002/jat.2550130311

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractOwing to the lack of sufficient theoretical and empirical information, the initial guidelines regarding animal carcinogenicity testing of chemicals adopted the most conservative approach possible. One of the recommendations was that non‐toxic chemicals be tested at a level as high as 5% of the diet. Since then, a wealth of information has been accumulated, which indicates that such highly exaggerated dosage levels are not only unnecessary but produce scientifically misleading and regulatorily detrimental results that impede the development and evaluation of useful chemicals, including human drugs. This paper presents the rationale supporting the necessity of revision of the outdated maximum level of dietary exposure from 5% to 1% or 1000 mg kg−1day−1when the test chemical is administered in drinking water or by g

ISSN:0260-437X    

DOI:10.1002/jat.2550130312

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY