摘要:

The accumulation and handling of mercury in the blood, kidneys, and liver were evaluated and compared in rats 5 min, 1 h, and 24 h after the intravenous administration of either a 0.25 μmol/kg dose of inorganic mercury or a 0.25 μmol/kg dose of inorganic mercury plus a 0.5 μmol/kg dose of glutathione (GSH) to determine the possible role of extracellular GSH and complexes of GSH and inorganic mercury in the renal uptake and transport of inorganic mercury. Significantly more of the injected dose of inorganic mercury was present in the blood of the rats injected with inorganic mercury alone than in the blood of the rats injected simultaneously with both inorganic mercury and GSH at all times evaluated after injection. Of the mercury remaining in the blood, however, significantly more mercury was in plasma fraction of blood in the rats injected with both inorganic mercury and GSH than in the plasma fraction of blood in the rats injected with inorganic mercury alone. The blood and plasma findings indicate that much of the mercury injected with GSH was in some complex that allowed the mercury to be cleared from the blood more readily and prevented the mercury from entering readily into red blood cells. The renal concentration of mercury was significantly greater in the rats injected with both inorganic mercury and GSH than in the rats injected with inorganic mercury alone at 5 min and 1 h, but not 24 h, after injection. This increased renal accumulation of mercury during the initial hours after injection was due mainly to enhanced uptake and/or retention of mercury in the renal cortex. Urinary excretion of mercury, over 24 h, was also slightly, but significantly, greater in the rats injected with both inorganic mercury and GSH simultaneously. These data indicate that coadministration of a nontoxic dose of inorganic mercury with a twofold higher amount (in moles) of GSH increases significantly the clearance of mercury from the blood and increases the renal cortical accumulation of inorganic mercury during the initial 1 h after injection. Moreover, the data in this study are consistent with the hypothesis that extracellular GSH is an important ligand to which mercuric ions bind, and that complexes of inorganic mercury and GSH in the blood and/or ultrafiltrate probably play a role in the renal uptake of some of the mercury in blood after exposure to mercuric compounds.

ISSN:0098-4108    

DOI:10.1080/15287399509531968

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The disposition of mercury in the blood, kidneys and liver was evaluated and compared in rats 5 min, 1 h, and 24 h after the intravenous administration of a 0.25 μmol/kg dose of inorganic mercury or a 0.25 μmol/kg dose of inorganic mercury plus a 0.5 μmol/kg dose of cysteine to determine the possible role of extracellular cysteine and complexes of cysteine and inorganic mercury in the renal uptake and transport of inorganic mercury. More inorganic mercury was present in the blood of the rats injected with inorganic mercury alone than in the blood of the rats injected simultaneously with both the inorganic mercury and cysteine during the first hour after injection. In addition, significantly more mercury was in the plasma fraction of blood in the rats injected with both inorganic mercury and cysteine than in the rats injected with inorganic mercury alone. These findings indicate that much of the mercury injected with cysteine was in some form of a complex that allowed the mercury to be cleared from the blood more readily and prevented the mercury from entering readily into the cellular components of blood. The renal concentration of mercury was significantly greater in the rats injected with both inorganic mercury and cysteine than in the rats injected with inorganic mercury alone 1 h, but not 24 h, after injection. This increased renal accumulation of mercury during the initial hour after injection was due mainly to enhanced uptake and/or retention of mercury in the renal cortex, although some of the enhanced accumulation of mercury also occurred in the outer stripe of the outer medulla during the first hour after injection. These data indicate that coadmin‐istration of a nontoxic dose of inorganic mercury with a twofold higher amount (in moles) of cysteine increases significantly the clearance of mercury from the blood and increases the accumulation of inorganic mercury in the renal cortex and outer stripe of the outer medulla during the initial 1 h after injection. In conclusion, the data in this study are consistent with the hypothesis that complexes of inorganic mercury and cysteine in the blood and/or ultrafiltrate probably play a role in the renal uptake of some of the mercury in blood after exposure to mercuric compounds.

ISSN:0098-4108    

DOI:10.1080/15287399509531969

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

In order to understand the splenic toxicity of aniline in rats, early interaction of aniline with erythrocytes and its subsequent deposition and covalent binding to macromolecules in target (spleen) and nontarget (liver) organs have been studied. Male Sprague‐Dawley (SD) rats were given 1 or 3 doses of 1 mmol/kg [14CJaniline hydrochloride (1 dose/d) by gavage and euthanized 24 h after the treatment. Among blood components, maximum radioactivity was found to be associated with red blood cells (RBCs). After 3 doses, there was 112, 79, and 67% increase in the radioactivity in the whole blood, RBCs, and hemolysate, respectively, in comparison to 1 dose. In comparison to RBCs, plasma had only 40 and 16% radioactivity after the administration of 1 and 3 doses, respectively. Spleen homogenate at 1 dose had one‐third of the radioactivity in the TCA precipitate, which increased to 40% at 3 doses, while the total radioactivity increased 256% over 1 dose. Liver, which had almost double the radioactivity on a per gram tissue basis compared to the spleen at one dose, did not show any appreciable increase in the radioactivity at three doses. However, radioactivity in the TCA precipitate of liver homogenate increased by 92 % after 3 doses. The iron content of the spleen in rats given 3 doses of [14C]aniline increased by 85% compared to the rats given just 1 dose. The iron content of liver did not show any change at three doses. These data thus demonstrate a dose‐dependent binding and accumulation of radioactivity in erythrocytes and spleen. These interactions, along with parallel increases in the iron content of the spleen, could be critical in the splenic toxicity of anilines.

ISSN:0098-4108    

DOI:10.1080/15287399509531970

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The chemopreventive properties of allyl sulfides on carcinogenesis may be related to the modulation of drug‐metabolizing enzymes involved in carcinogen activation or detoxica‐tion. In order to investigate the effects of diallyl sulfide (DAS) and diallyl disulfide (DADS) on intestinal and hepatic drug‐metabolizing enzymes, rats were fed a diet containing 0.2% of either allyl sulfide. The DADS enhanced intestinal epoxide hydrolase (EH) and cytochrome P‐450 (P‐450) 2B1/2 protein levels and the activities of pentoxy‐ and benzyl‐oxyresorufin O‐dealkylases, arylhydrocarbon hydroxylase, microsomal epoxide hydrolase, p‐nitrophenol UDP‐glucuronyl transferase and glutathione S‐transferase, and decreased nitrosodimethylamine demethylase activity. In liver, DADS produced similar effects and, in addition, increased P‐450 1A1/2 protein level and phenoxazone metabolizing activities (ethoxy‐ and methoxyresorufin O‐dealkylases), p‐hydroxybiphenyl UDP‐glucuronyl transferase, and decreased P‐450 2E1 level. The DAS enhanced only EH activity in the small intestine and induced P‐450 2B1/2 and epoxide hydrolase protein levels. In liver, DAS produced similar effects as DADS. The different effects of DAS on intestinal drug‐metabolizing enzymes, compared to liver, could be ascribed to less metabolism of this compound in small intestine. It is also suggested that DAS and DADS may not yield the same metabolites and therefore would have different effects on intestinal drug‐metabolizing enzymes.

ISSN:0098-4108    

DOI:10.1080/15287399509531971

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The hepatocarrtnogen'icity of trichloroethylene (TRI) in mice has been attributed to a metabolite, trichloroacetate (TCA). Rats of various strains appear to be resistant to TRI‐induced hepatocarcinogenesis and produce lower peak concentrations of TCA. Mice, however, also form significant amounts of another carcinogenic metabolite, dlchloroacetate (DCA). The present study was conducted to investigate the interspecies differences in the metabolism of TRI between the mouse, rat, and dog and to gain further insight into the role metabolic factors may play in the apparent species specificity of liver tumor induction by TRI. Fischer 344 rats and beagle dogs were dosed orally with TRI and blood was analyzed for TRI, DCA, TCA, and trichloroethanol (TCE). Data on the metabolism of TRI in mice have been previously published. Limited data are available on the metabolism of TRI In humans. Dogs produce higher peak concentrations and have a larger area under the concentration‐time curve (AUC) for TCA as compared to rats given similar doses of TRI. Dichloroacetate was not found in measurable concentrations, that is, above 4 nmol/ml, the minimal quantifiable concentration, in the blood of either rats or dogs. Appreciable concentrations of DCA were found in the blood of mice administered TRI In previous studies. Trichloroethanol was found to be present in the blood, urine, and bile, primarily as the glucuronide conjugate. In all species, peak TCA concentrations were observed beyond the disappearance of TRI. The AUC for TCE glucuronide is consistent with its acting as a precursor for TCA and probably contributes to the continued increase in TCA concentration after TRI disappears from the system. Investigations into the binding of TCA to plasma constituents in the rat, dog, mouse, and human suggest that binding also plays a role in species differences in the distribution and elimination of TCA.

ISSN:0098-4108    

DOI:10.1080/15287399509531972

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

We demonstrate for the first time that diethylstilbestrol (DES), a synthetic estrogen, is converted by nuclei to histone‐binding metabolite(s). Reaction of [3H]DES with nuclei in the presence of cumene hydroperoxide or NADPH revealed binding of [3H]DES to histone nuclear proteins. Cel electrophoresis experiments revealed that all five histones, 1, 2A, 2B, 3, and 4, were irreversibly bound to [3H]DES. Histones 1 and 3 were more susceptible to the attack by [3H]DES quinone, a metabolite of DES, than histones 2A, 2B, or 4. The kinetic constants,KmandVmax, of this binding reaction in the presence of cumene hydroperoxide were 10 μM and 750 pmol/mg protein/30 min, respectively. This binding was significantly inhibited by cytochromes P‐450 inhibitors. Low‐molecular‐weight thiols, such as glu‐tathione and cysteine, or thiol modifiers, such as n‐ethylmaleimide, dithionitrobenzoic acid, and hydroxymercuric benzoate, drastically inhibited binding of [3H]DES quinone to histone 3. The binding of [3H]DES metabolites to both transcriptionally active and inactive chromatin histone proteins was observed. We conclude that DES is metabolized to histone‐binding metabolites, presumably by nuclear cytochromes P‐450. DES quinone may be one of the histone‐binding DES metabolites. These data suggest that an analogous in vivo modification in the transcriptionally active chromatin histones by DES metabolites may influence gene function.

ISSN:0098-4108    

DOI:10.1080/15287399509531973

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Triphenyl phosphite (TPP) is a weak acetylcholinesterase inhibitor and a type II organophosphorus compound‐induced delayed neurotoxic agent. The current study examined the cognitive effects of a single 250 mg/kg ip dose of TPP administered to either 3‐mo‐ or 1‐yr‐old male Sprague‐Dawley rats. Starting 4 d after TPP administration, the rats began training on a T‐maze spatial alternation task for food reinforcement. Over five sessions of acquisition training, the TPP‐treated rats showed significantly lower alternation scores than controls. There was no difference in spatial alternation performance in the first session, when both groups were performing at near‐chance levels. In sessions 2–5, the controls improved dramatically to an average of 853 ± 3.2% correct, while the TPP‐treated rats did not significantly change, with 69.7 ± 3.1 percent correct. During sessions 2 and 3 there was a significant TPP treatment‐related deficit. This TPP‐induced choice accuracy deficit was persistent in that it was seen well after the acute exposure. With continued training the TPP‐exposed rats were able to learn the task as well as controls. There were no significant TPP effects on response latency. These data show that acute TPP administration has persistent effects of impairing T‐maze learning that do not appear to result from effects on motor function.

ISSN:0098-4108    

DOI:10.1080/15287399509531974

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Short‐term (96‐h) tests on Xenopus laevis embryos are advocated for rapid screening of teratogens, as an alternative to the use of mammals. The objective of the present investigation was to determine whether extending the short‐term tests beyond 96 h would detect the teratogenicity of chemicals that would otherwise be missed by the short‐term tests. Lead teratogenicity was examined in Xenopus, using lead concentrations of 0.02, 0.05, 0.1, 0.5, 1.0, and 3.0 mg/L, which bracket the U.S. Environmental Protection Agency (EPA) maximum allowable concentration of 0.05 mg/L in water. Short‐term exposure times were 72 or 96 h, starting on d 1, 2, or 3 postfertilization, while long‐term exposure covered d 1 through metamorphosis. Short‐term exposure resulted in neural tube defects (when exposure included d 1 and/or d 2) and tail curvatures, but only at the higher lead concentrations (1 and 3 mg/L). Lower lead concentrations produced no malformations upon short‐term exposure, and this corresponded with the absence of tissue lead uptake. On the other hand, long‐term exposure to lead (>3 wk) resulted in the delayed appearance of lordoscoliosis at low lead concentrations (0.02–0.1 mg/L). The delayed appearance of lordoscoliosis corresponded roughly with the attainment of stable lead tissue levels, and this malformation persisted after metamorphosis. Thus, short‐term observation tests alone may fail to detect the teratogenicity of low concentrations of environmental chemicals, and may result in the setting of inappropriately liberal exposure standards.

ISSN:0098-4108    

DOI:10.1080/15287399509531975

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The chronic effects of secondary‐treated effluent from a thermomechanical pulp (TMP) mill were assessed by means of long‐term and short‐term laboratory toxicity tests. The effluent used for the tests was sampled at a western Canadian mill using mostly softwoods and <10% recycled fiber as furnish. In the long‐term test, the effects of the effluent on the life cycle of fathead minnows (Pimephales promelas.) were studied. In this experiment, which began with the egg stage and continued through to sexual maturity and reproduction, the fish were exposed in the laboratory to well water (control) and five concentrations (1.25%, 2.5%, 5%, 10%, or 20%) of effluent for 202 d. None of the effluent concentrations significantly affected the hatching of the eggs, the mortality, weight, length, gonad size, gender balance, and reproduction of the hatched fish, the prevalence of gross morphological and histopathological changes, and the hatchability of the first generation eggs. Two short‐term tests, each lasting 7 d, were also performed. In these tests, 100% effluent caused no change in the survival/growth of minnow larvae or in the survival/reproduction of Ceriodaphnia.

ISSN:0098-4108    

DOI:10.1080/15287399509531976

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399509531967

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor