摘要:

Caffeine, when administered in moderate (30 mglkg ? d) or high (60 mg/kg ? d) doses during pregnancy, was shown to cause significant fetal growth retardation of both sexes. Mortality rate at or soon after birth was significantly higher and litter size significantly lower in the litters treated with 60 mg. The subsequent growth rates were also affected. The experimental pups grew more slowly, with growth plateauing at the same age resulting in smaller adults. The male offspring when subjected to short‐term stress (one session) in adulthood showed an intact emergency response, demonstrating an adequate ability to react to a sudden environmental change. A significant decrease in 3ß‐hydroxysteroid dehydrogenase (3ß‐HSD) activity, and consequent reduction in testosterone biosynthesis, in the fetal testes at d 18 and 20 of gestation was also found for both doses of caffeine. Low 3ß‐HSD activity persisted to adulthood in the group receiving 60 mg.

ISSN:0098-4108    

DOI:10.1080/15287398709531046

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Propylene glycol dinitrate (PGDN), a major constituent of a liquid torpedo propellant, produces incoordination and impairment of balance in humans. This study was conducted to evaluate the rat as a model for PGDN‐induced motor performance decrement, and to determine if direct application of PGDN onto neural tissue is a useful alternative to other routes of exposure. PGDN was injected onto the cisterna magna (ic) of adult Sprague‐Dawley rats trained on the accelerod, a test of motor performance. Three groups of 13–14 male rats each received a single dose of either 5 or 10 μl PGDN or 25 μlsterile saline (control) while anesthetized with halothane. Accelerod performance was measured 12 min after ic injection, then hourly for 6 h, and at 24 h. Injections were evaluated using a five‐stage screening criterion to eliminate grossly traumatized subjects, to verify the accuracy of the injection, and to determine the extent of mechanical damage. Eighteen out of 41 subjects passed the five‐stage screen. A significant decrease in periormance occurred during the first 2 h following injection of 10 μl PGDN compared to the control and the 5‐μl groups. No significant differences were seen between the 5‐μland control groups. These data confirm previous findings of PGDN‐induced changes in human motor performance, suggesting that the rat may be a useful model for further PGDN neurobehavioral assessment. The data also indicate that ic injection may be an effective alternative to other routes of exposure for materials with appropriate chemical and biological properties if an evaluation screen is used.

ISSN:0098-4108    

DOI:10.1080/15287398709531047

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Cyclophosphamide is an alkylating antineoplastic drug and has been shown to impair spermatogenesis after chronic exposures. The purpose of this investigation was to determine the effect of cyclophosphamide on sperm production in hamsters following subacute intraperitoneal (ip) exposures. The Syrian hamster, Mesocricetus auratus, aged 10–11 wk, received single daily ip doses for 4 d ranging from 10 to 250 mg cyclophosphamide/kg body weight. Control hamsters received an equivalent volume of phosphate‐buffered saline solution. Testis weight, caudal sperm number, and sperm morphology were monitored for 12 wk. Cyclophosphamide failed to induce sperm abnormalities. Testis weight and sperm count were slightly suppressed at wk 1 and 4 before returning to normal at wk 12. This study showed that subacute doses of cyclophosphamide in hamsters did not significantly affect the sperm production as previously reported in other animals.

ISSN:0098-4108    

DOI:10.1080/15287398709531048

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Previous investigations have demonstrated that the cytosolic protein metallothionein (MT) is induced not only by exposure to certain heavy metals but also by a variety of other factors, including environmental stress. While MT synthesis has been observed with exposure to cold temperatures, there is a paucity of data concerning the influence of cold on heavy‐metal toxicity. The present investigation focused on the influence of metal and cold pretreatments on the acute toxicity of cadmium. Mortalities of 80% and 100% were observed for mice orally administered challenge doses of 100 mg Cd/kg and 150 mg Cd/kg, respectively. To determine a protective cadmium pretreatment dose, animals were administered 2.5, 5, 10, 20, 25, and 50 mg Cd/kg 24 h prior to cadmium challenge. In animals pretreated with 10 mg Cd/kg, mortalities of 20% and 70% were observed with the respective challenge doses. Immediately following cold stress (4°C, 12 h), mortalities of 30% and 90% were observed with cadmium challenge doses of 100 and 150 mg Cd/kg, respectively. Significant correlations were demonstrated between induced hepatic MT concentrations and cadmium pretreatment (r = 0.99), as well as cold pretreatment (r = 0.87). Results of this investigation indicate that Stressors, such as cold, influence the acute toxicity of cadmium to the same magnitude as metal pretreatment. This induced tolerance to cadmium was attributed, in part, to the induction of MT synthesis. Furthermore, the induced levels of MT resulting from cold stress may confound the simplistic approach of using MT as a biological monitor of occupational exposure to cadmium.

ISSN:0098-4108    

DOI:10.1080/15287398709531049

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The influence of Aroclor 1254 (ARO) treatment or pair‐feeding (PF) on gluconeogen‐esis and urea synthesis and on isolated hepatic mitochondria was studied in rats of different ages. ARO (300 mg/kg, po on 4 consecutive days) induced variable weight loss in young (153 ± 10 g (initial wt), ‐10.9%), intermediate‐age (195 ± 10 g, ‐17.0%), and old (232 ± 23 g, ‐4.9%) rats. Isolated mitochondria contained equal amounts of cytochromes aa3,b,c1and c with exception that c1and c were lower in the young ARO rats than in the PF controls. Mitochondria from ARO rats, which lost more weight than ad libitum‐fed (AF) rats, showed suppression of ADP‐stimulated H+and oxygen uptake and succinate plus valinomycin maximal swelling in a potassium acetate and sucrose medium. Mitochondria from young ARO rats absorbed less incident light than mitochondria from PF or AF rats. Maximally swollen mitochondria from intermediate‐age ARO rats, contracted more rapidly with antimycin addition than those from PF or AF controls. These findings showed greater permeability of ARO mitochondria to impermeable and accumulated ions. In contrast, mitochondria from ARO rats without significant weight loss showed activation of ADP‐stimulated H+and oxygen uptake and maximal swelling in comparison to mitochondria from AF and PF rats, but contracted like these controls after the antimycin addition.

ISSN:0098-4108    

DOI:10.1080/15287398709531050

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The in vivo‐in vitro DNA repair and DNA replication assay in mouse hepatocytes has promise as a short‐term test for detecting potential mouse liver carcinogens. In addition, this assay may provide information on the mode of action of known hepatic carcinogens. The induction of DNA repair is clearly a response to hepatic DNA damage. However, it is unclear whether induction of replicative DNA synthesis (S phase) represents regenerative hyperplasia in response to hepatotoxicity or is a result of direct mitogenic stimulation of the hepatocytes by the test compound. The objective of the present study was to examine the relationship between hepatotoxicity, which was assessed by measuring serum concentrations of glutamic‐oxalacetic transaminase (SCOT), glutamic‐pyruvic transaminase (SCPT), alkaline phosphatase (AP), and gammaglutamyl transferase (CGT), and induction of S phase following either single or multiple doses of the model mouse hepatocarcinogen carbon tetrachloride (CCI4).

ISSN:0098-4108    

DOI:10.1080/15287398709531051

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

5‐Hydroxymethyl‐2‐furaldehyde (HMF), is a major product of sugar degradation found in food and solutions used in parenteral nutrition. Labeled [14C]HMF was synthesized by dehydration of [14C]fructose on ion‐exchange resin and administered per os (po) and intravenously (iv) to rats. Metabolic balance of radioactivity demonstrated that HMF or its metabolites are rapidly eliminated in the urine with a recovery of 95–100% after 24 h. Literature reported, in some cases, 50% retention in the body. HMF was completely converted to two metabolites, which have been identified by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) as 5‐hydroxymethyl‐2‐furoic acid and N‐(5‐hydroxymethyl‐2‐furoyl)glycine. Administration of high doses of HMF showed a similar rapid elimination, but a proportional reduction of the amount of the glycine conjugate produced. Whole‐animal‐body autoradiography confirm that shortly after administration radioactive material was present in the liver but was mostly in the kidney and the bladder. The only significant difference between po and iv administration was the presence of a higher level of radioactive material in the brain of iv‐treated rats.

ISSN:0098-4108    

DOI:10.1080/15287398709531052

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Immunological effects of manganese chloride (MnCl2) were determined in male CD‐1 mice injected (ip) daily with MnCl2(0, 1, 3, or 10 mg/kg) for 4 wk. Liver and spleen weights increased in the 10‐mg/kg MnCl2treatment group. The weights of thymus, kidney, and adrenal glands were not affected by MnCl2treatment. No significant differences in peripheral erythrocyte or leukocyte counts were observed; however, packed cell volumes decreased in the medium‐ and high‐dose groups. Manganese treatment significantly increased the uptake of [3H]thymidine (3H‐TdR) by cultured splenic cells. The lymphoproliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A) increased at all levels of MnCl2exposure. No differences in the responses to lipopolysaccharide (LPS) were observed. Mixed lymphocyte responses increased significantly with exposure to 10 mg MnCl2/kg. Another immunological alteration induced by MnCl2was a dose‐dependent immunosuppressive effect on the development of antibody‐forming cells. The production of anti‐sheep red blood cell antibody (α‐SRBC) nearly ceased following exposure to 10 mg MnCl2/kg. This effect was apparently reversible, as the number of plaque‐forming cells in the 10‐mg/kg treatment group increased after MnCl2treatment had been halted for 2 wk. The a‐SRBC titer also decreased significantly in the 10‐mg/kg treatment group, corresponding to the reduction of antibody‐producing cells. MnCl2treatment was immunomodulatory in male CD‐1 mice,asindicated by the increase in mitogen and mixed lymphocyte responses and decrease in antibody production.

ISSN:0098-4108    

DOI:10.1080/15287398709531053

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine > cefazolin > cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively des‐acetylated in rabbits to a less microbiologically active metabolite, desacetylcepha‐lothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine > cefazolin > cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetyl‐cephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.

ISSN:0098-4108    

DOI:10.1080/15287398709531054

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287398709531045

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor