摘要:

The aim of the present study is twofold: to establish the response of hepatic machinery of plasma protein biosynthesis to cholera intoxication, and to examine the same response of alloxan‐diabetic hepatocytes with minimal capacity of synthesis of plasma proteins. Direct lesion of hepatic plasma membranes via ip administration of cholera toxin to male rats resulted in a typical acute‐phase response (APR) of plasma proteins, which had regressed to levels similar to those of healthy controls approximately at 240 h postintoxication. The d 2 response to a single 0.16 mg/kg body weight dose was typified by a 23% reduction in the level of albumin, but a 6‐ and 24‐fold increase in the levels of fibrinogen and alpha‐1‐acid glycoproteins, respectively. This response was similar (in direction but not in magnitude) to the acute‐phase reaction to a simple subcutaneous administration of cartageenan. The intoxication was accompanied by a massive leakage, into the peritoneal cavity, of plasma fluid, which embraced the complete profile of acute‐phase reactants. A three‐step mechanism is proposed to account for the observations as follows: (1) There is a rapid formation of a stable complex between subunit B of the toxin and ganglioside GM1 of hepatic plasma membrane. An APR is induced in response to the alteration(s) of hepatic plasma membranes. (2) The release, from the choleragen‐membrane complex, of polypeptide A1 and its subsequent penetration of the hepatic membrane result in both activation of adenylate cyclase and increased vascular permeability of hepatic membranes. This leads, in turn, to exudation of components of plasma fluid in the peritoneal cavity of intoxicated rats. An alternate rationale for this exudation is the slow leakage of plasma proteins out of the blood vascular system (possibly through microvesicles) into the peritoneal cavity of cholera intoxicated rats. The spectrum of acute‐phase hepatic secretory components was mirrored in the corresponding peritoneal exudate. (3) The increased hepatic membrane flow provides the continued renewal of plasma membrane proteins required for its eventual repair by either endocytosis or sloughing off the toxin‐bound membrane segments into the circulatory system, thus producing regression of APR.

ISSN:0098-4108    

DOI:10.1080/15287399309531696

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399309531695

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The disposition of dichloroacetic acid (DCA) was investigated in Fischer 344 rats over the 48 h after oral gavage of 282 mg/kg of 1‐ or 2‐[14C]‐DCA (1‐DCA or 2‐DCA) and 28.2 mg/kg of 2‐DCA. DCA was absorbed quickly, and the major route of disposition was through exhalation of carbon dioxide and elimination in the urine. The dispositions of 1‐ and 2‐DCA at 282 mg/kg were similar. With 2‐DCA, the disposition differed with dose in that the percentage of the dose expired as carbon dioxide decreased from 34.4% (28.2 mg/kg) to 25.0% (282 mg/kg), while the percentage of the radioactivity excreted in the urine increased from 12.7 to 35.2%. This percentage increase in the urinary excretion was mostly attributable to the presence of unmetabolized DCA, which comprised more than 20% at the higher dose and less than 7% at the lower dose. The major urinary metabolites were glycolic acid, glyoxylic acid, and oxalic acid. DCA and its metabolites accumulated in the tissues and were eliminated slowly. After 48 h, 36.4%, 26.2%, and 20.8% of the dose was retained in the tissues of rats administered 28.2 and 282 mg/kg of 2‐DCA and 282 mg/kg of 1‐DCA, respectively. Of the organs examined, the liver (4.9–7.9% of dose) and muscle (4.5–9.9%) contained the most radioactivity, followed by skin (3.3–4.5%), blood (1.4–2.6%), and intestines (1.0–1.7%). One metabolite, glyoxylic acid, which is mutagenic, might be responsible for or contribute to the carcinogenicity of DCA.

ISSN:0098-4108    

DOI:10.1080/15287399309531697

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The interaction of ethanol (EtOH) and cyclohexanone (CHN) metabolism was studied to demonstrate the influence of alcohol beverage in cyclohexanone poisoning. Rabbits were administered CHN and EtOH separately or together, and the plasma concentration of CHN and cyclohexanol (CHL), a metabolite of CHN, and blood concentrations of EtOH were measured at various times. When CHN alone was administered orally, the time to maximum plasma concentration (Tmax) of CHN was as short as 15 min, but that of CHL was 120 min. The short Tmaxof CHN was considered to be due to the first‐pass effect. The plasma concentration of CHL was much greater than that of CHN. On the other hand, when the same amount of molar CHL was administered in rabbits for sake of comparison, only small amounts of CHN were detected in plasma. The interconversion between CHN and CHL at the time of equilibration tended to shift predominantly toward the formation of CHL, whose plasma concentration ratio was about 1:6 to 1:8.

ISSN:0098-4108    

DOI:10.1080/15287399309531698

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Neonatal exposure to certain xenobiotics has been shown to alter hepatic metabolism in adult rats in a manner that indicates long‐term changes in enzyme regulation. Previously, we have observed changes in adult testosterone metabolism and in cytochrome P‐450 (P‐450) mRNA levels in animals neonatally exposed to phenobarbital (PR) or diethylstilbestrol (DES). In order to test for other enzyme alterations, we used Western blot procedures for specific P‐450s to analyze hepatic microsomes from adult rats (24 wk old) that had been exposed neonatally to DES, PB, 7,12‐dimethylbenz[a]anthracene (DMBA), or pregnenolone 16α‐carbonitrile (PCN). The most striking effects were observed in the DES‐treated males: P‐4502C6 and an immunologically similar protein were increased 60 and 90%, respectively, relative to control values, but P‐4503A2 was decreased by 44%. No changes were observed in the DES‐treated males in levels of P‐4502E1, P‐4502B, or the male‐specific P‐4502C13. Adult males neonatally treated with PB had 150% increase in levels of anti‐P4502B‐reactive protein without significant changes in the other enzymes. The DES‐ and DMBA‐treated females had increased levels of the female‐specific P‐4502C12 of 38 and 48%, respectively, but no other observed alterations. The results confirm that neonatal exposure to DES or PB can cause alterations in adult hepatic cytochrome P‐450 levels but show that these chemicals act on different enzymes. Neonatal DMBA resulted in changes in adult females similar to those produced by the synthetic estrogen DES, but did so at about two‐thirds lower dose.

ISSN:0098-4108    

DOI:10.1080/15287399309531699

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

A crude extract of the ichthyotoxic phytoflagellate Prymnesium patelliferum strongly inhibited the uptake of neurotransmitters into isolated nerve endings (synaptosomes) and synaptic vesicles. These systems were about 100 and 10 times more sensitive toward the algal toxin, respectively, than a standard hemolysis assay often used for testing the toxicity of Prymnesium spp. and other ichthyotoxic algae. Prymnesium patelliferum grown in phosphorus‐deficient (‐P) medium was about five times more active than when grown in phosphorus sufficient (+ P) medium. The inhibition ratio between the high‐affinity synaptosomal uptake of L‐glutamate and γ‐aminobyturic acid (CABA) was 1/2.7 for the ‐ P culture and 1/1.9 for the + P culture. The inhibition ratios for the low‐affinity vesicular uptake of L‐glutamate, GABA, and dopamine (DA) were 1/5.8/0.3 and 1/1.7/0.2, respectively. The synaptosomal transport of L‐glutamate is a rapid, simple, and sensitive test method for toxicity determination of Prymnesium spp. and will be a useful tool in the further isolation and purification of the toxic principles of this and other related algae. It is suggested that the toxin interferes with ion channels or acts as an ionopore.

ISSN:0098-4108    

DOI:10.1080/15287399309531700

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The effects of subchronic administration of captafol were studied in B6C3F1mice given dose levels of 0, 0.3, 0.625, and 1.25% in the diet for 12 wk. There was a dose‐related decrease in body weight gain during the 12‐wk experiment and a loss of body weight in the 1.25% group of both sexes. Whiles the mice given captafol consumed less diet than the control mice, this was not directly dose‐related. The relative weights of liver demonstrated a tendency for dose‐dependent increase. Light‐microscopic examination revealed cytoplasmic vacuolar degeneration, depending in severity on the dosage, in the livers of both sexes given captafol. In conclusion, the findings obtained from the present subchronic toxicity study indicated the liver to be a primary target organ.

ISSN:0098-4108    

DOI:10.1080/15287399309531701

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The toxicokinetics of d‐limonene were studied in human volunteers exposed by inhalation (2 h, work load 50 W) in an exposure chamber on three different occasions. The exposure concentrations were approximately 10, 225, and 450 mg/m3d‐limonene. The relative pulmonary uptake was high, approximately 70% of the amount supplied. The blood clearance of d‐limonene observed in this study, 1.1 l kg−1h−1, indicates that d‐limonene is metabolized readily. About 1% of the total uptake was eliminated unchanged in the expired air after the end of exposure, while approximately 0.003% was eliminated in the urine. A long half‐time in blood was observed in the slow elimination phase, which indicates accumulation in adipose tissues. A decrease in vital capacity was observed after exposure to d‐limonene at a high exposure level. The subjects did not experience any irritative symptoms or symptoms related to the central nervous system (CNS).

ISSN:0098-4108    

DOI:10.1080/15287399309531702

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The toxicity test of onion coat colorant (OC), a food colorant extracted from onion (Allium cepa L.), was undertaken using (C57BL/6 × C3H)F1mice of both sexes for the safety assessment of this product. The acute toxicity test was performed by administration of OC suspended in corn oil by gavage at doses of 2500, 5000, 7500, and 10,000 mg/kg body weight to groups of 5 or 6 males and 6 or 7 females, maintained for 14 d. Six of 12 females dosed at 10,000 mg/kg body weight and 3 of 11 females dosed at 7500 mg/kg body weight were dead before the end of the study, indicating that the tolerated dose of OC was between 7500 and 5000 mg/kg body weight. The subacute toxicity test of OC was examined using 123 mice of both sexes (62 males and 61 females) by feeding a diet mixed with OC at concentrations of 5, 2.5, 1.25, 0.6, and 0.3% for 90 d. All mice tolerated these doses of OC well. The body weight gains of male and female mice were not affected by the treatment. Histopathological examinations showed that hyperplastic changes in the esophagus, forestomach, pancreas, cervix, and endometrium of mice were found in treated and control mice. However, their incidences were not related to the dose of OC. Moreover, only a spontaneous ovarian teratoma was found in an OC‐treated mouse. These results suggest that OC has no acute and subacute toxic effects in mice.

ISSN:0098-4108    

DOI:10.1080/15287399309531703

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399309531694

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor