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PubMed1989

Micronucleus induction in mouse bone marrow by phenacetin administered intraperitoneally or orally.

The extent and time course of induction of micronucleated polychromatic erythrocytes (MNPCEs) in mouse bone marrow were examined after administration of phenacetin as an insoluble suspension in olive oil by intraperitoneal injection (i.p.) or gastric intubation (p.o.) to 2 strains of mice, MS/Ae and CD-1, at doses up to 1200 mg/kg. The toxicity of phenacetin and the sensitivity of micronucleus induction differed in the 2 strains, but there was little difference in the extent of MNPCEs induced by the 2 administration routes.

Animals↗

PubMed1989

Effect of route of administration in the micronucleus test with potassium bromate.

The effect of intraperitoneal injection (i.p.) versus oral gavage administration (p.o.) of potassium bromate was examined using the micronucleus test in 2 strains of male mice (MS/Ae and CD-1). First, a small acute toxicity test and a pilot micronucleus experiment were performed to determine the appropriate dose range and sampling time for the full-scale micronucleus test. The full-scale test was carried out using doses of 18.8, 37.5, 75, and 150 mg/kg in the i.p. test and of 37.5, 75, 150, and 300 mg/kg in the p.o. test. The sampling time was 24 h for both mouse strains. Potassium bromate induced micronucleated polychromatic erythrocytes (MNPCEs) dose-dependently by both routes of administration in both mouse strains. No distinct difference in route of administration was observed in the test with MS/Ae mice. In CD-1 mice more MNPCEs were induced by the i.p. route than by the p.o. route.

Administration, Oral↗

PubMed1990

Influence of treatment to sacrifice time and the presence of BrdUrd on chemically-induced aberration rates in mouse marrow cells.

4 chemicals, with various modes of clastogenic action were used to evaluate induced chromosomal aberrations in mouse bone marrow at different times after intraperitoneal injection. Aberration frequencies induced by mitomycin C, cyclophosphamide and dimethylbenz[a]anthracene increased with increasing time between treatment and sampling until those time points (approximately 18 h) when significant proportions of second-division metaphases were among the cells being scored; this increase was not obvious following treatment with 4-nitroquinoline 1-oxide. When BrdUrd tablets were implanted prior to treatment and scoring was restricted to first-division metaphases, aberration rates continued to increase for as long as 24 h post-treatment. The presence of BrdUrd did not affect significantly the rate of aberration induction by the chemicals. Our data indicate that the sensitivity of the in vivo mouse marrow assay for clastogenic chemicals can be greatly increased by utilizing BrdUrd to insure the scoring of only first-division metaphases at post-treatment times of approx. 18 h.

4-Nitroquinoline-1-oxide↗

PubMed1991

The effect of exposure to nicotine, carbon monoxide, cigarette smoke or cigarette smoke condensate on the mutagenicity of rat urine.

Cigarette smokers have been reported to void urine which is more mutagenic than that voided by non-smokers, but the specific urinary mutagen(s) have not been identified. Since mechanistic studies are best performed in animal models, the objective of this study was to determine if a model to study the role of cigarette smoke and its components in urinary mutagenicity could be developed in rats. XAD-2 resin was used to concentrate the urine and the microsuspension modification of the Ames test used to quantify mutagenicity. Nicotine administered by intraperitoneal injection at 0.8 mg/kg (the maximum tolerated dose) or inhalation of carbon monoxide for 14 days at the maximum tolerated dose (1800 ppm, resulting in 68% carboxyhemoglobin) did not increase urinary mutagenicity. Cigarette smoke condensate (CSC) prepared by electrostatic precipitation of mainstream smoke increased urinary mutagenicity at doses of 100 and 200 mg/kg when administered acutely by either i.p. injection or gavage, verifying that the assay system was capable of detecting cigarette smoke-related mutagens in the urine. However, cigarette smoke administered by the appropriate route of exposure, nose-only inhalation, for 1, 7, 14 or 90 days (1 h per day) did not increase urinary mutagenicity. The smoke concentration administered was at or near the maximum tolerated dose as evidenced by carboxyhemoglobin concentrations of approximately 50%, and of 10% or more weight loss in exposed animals. Thus, although cigarette smoke condensate is mutagenic in vitro and mutagenic urine was observed when rats were given high doses of CSC by inappropriate routes of administration, acute or subchronic inhalation exposure to the maximum tolerated dose of whole cigarette smoke did not increase urinary mutagenicity in rats. These results indicate that the rat may be an inappropriate model to study urinary mutagenicity following the inhalation of tobacco smoke.

Administration, Inhalation↗

PubMed1986

Fish and antibiotics: pharmacokinetics of sulphadimidine in carp (Cyprinus carpio).

Pharmacokinetics, metabolism and clearance of sulphadimidine (SDM) were studied after a single intraperitoneal injection of SDM in carp at 20 degrees C. SDM was acetylated and hydroxylated to a small extent. The main metabolite was N4-acetyl derivative amounting only 2% of the total drug dose excreted; hydroxylation was less important (0.41% of the dose). The elimination half-life for SDM in carp was 17.5 h. The clearance values for SDM and its metabolites were equivalent. The importance of pharmacokinetic studies in different fish species is discussed.

Animals↗

PubMed1991

Testosterone induces lymphopenia in turtles.

Owing to the possible role of sex steroids in the immune-neuroendocrine interactions found in lower vertebrates, we attempted to delineate the effect of testosterone propionate on peripheral blood (PB) and the lymphoid organs of the turtle Mauremys caspica. A single intraperitoneal injection of 200 micrograms/g body weight produced thymic involution and intense lymphopenia in the spleen and, less severely, in the PB compartment. It is suggested that lymphocyte redistribution may occur among the various compartments of the body as the main effect of hormone-induced lymphocyte redistribution, although the mechanism in reptiles and mammals is not yet understood.

Animals↗

PubMed1992

Neutrophil, glass-adherent, nitroblue tetrazolium assay gives early indication of immunization effectiveness in rainbow trout.

Neutrophil activity in rainbow trout (Oncorhynchus mykiss) is increased upon antigenic stimulation with the Yersinia ruckeri O-antigen bacterin. The characteristics of neutrophil attachment to glass and nitroblue tetrazolium (NBT) staining were used to determine the effectiveness of immunization programs with fingerling rainbow trout. Fish immunized by intraperitoneal injection with doses of 100, 10, or 1 microgram of the bacterin showed the highest responses in that order in numbers of glass adherent, NBT-positive neutrophils. Studies on the kinetics of the occurrence of numbers of glass-adherent, NBT-positive staining cells from the fish injected with the 10 micrograms dose showed the numbers of positive cells were largest on Day 2 after injection. The specific immune response was confirmed by demonstrating the presence of plaque-forming cells by the passive hemolytic plaque assay and the rise in humoral antibody titers by passive hemagglutination 12 days after injection. The effects of immunization in trout could be detected earlier by using the neutrophil glass adherence and NBT reduction assays than by using assays based on observations of the specific immune response.

Animals↗

PubMed1992

N-methyl-D-aspartate antagonists suppress the development of frog symmetric monocular optokynetic nystagmus observed after unilateral visual deprivation.

In monocular vision, frogs display a unidirectional optokinetic nystagmus (OKN), reacting only to temporal-nasal (T-N) stimulation. The OKN N-T component is almost absent. However, prolonged monocular visual deprivation by unilateral eyelid suture provoked the appearance of the N-T component. The analysis of search coil recordings showed that the slow phase velocity gain of both T-N and N-T components became similar. Chronic administration of N-methyl-D-aspartate (NMDA) antagonists for the duration of deprivation prevented the appearance of a symmetrical monocular OKN in frogs: following repeated intraperitoneal injections of either MK 801, CGS 19755 or intrapretectal microinjections of 2-amino-5-phosphonovalerate (APV), the N-T component did not appear, and OKN remained asymmetrical. Thus NMDA receptors appear to be involved in the control of the plasticity process which allows monocular OKN of adult lower vertebrates to become symmetrical.

2-Amino-5-phosphonovalerate↗

PubMed1982

Protection against experimental allergic neuritis with silica quartz dust.

Lewis rats sensitized against peripheral nervous system antigens can be protected against experimental allergic neuritis (EAN) by the intraperitoneal injection of silica quartz dust. Two doses of 200 mg silica given 8 and 11 days post-inoculation (dpi) protected against the development of both clinical and pathological disease. A single dose of 200 mg silica 8 dpi gave significant protection against clinical disease but all animals developed pathological signs. A single injection of 200 mg silica 11 dpi, after the onset of early signs, protected against further progression of disease. The protection was long lasting. Given the known toxic effects of silica for macrophages, these results would support the conclusion that macrophages function during the effector stage in the clinical and pathological expression of EAN in the Lewis rat.

Animals↗

PubMed1990

Activity of urethane and N,N-dimethylurethane in the mouse bone-marrow micronucleus assay: equivalence of oral and intraperitoneal routes of exposure.

Urethane is shown to be active in the mouse bone-marrow micronucleus assay when administered as a single dose by either gavage or intraperitoneal injection. The magnitude of the response using the two routes was not statistically significantly different. N,N-Dimethylurethane (DMU) is shown to be mutagenic to Salmonella and active in the bone-marrow micronucleus assay by both routes of administration. The activity of DMU in the bone marrow precludes elimination of ethanol, yielding cyanate ion, as an explanation for the micronucleus-inducing activity of urethane.

Administration, Oral↗

PubMed1991

Activity of aniline in the mouse bone marrow micronucleus assay.

Aniline gave a positive response in the mouse bone marrow micronucleus assay 24 h after the second of two intraperitoneal injections of 80% of the median lethal dose (MLD). Negative results were observed at lower dose levels and at earlier and later sampling times. The significance of this unique activity profile is discussed within the context of the non-carcinogenicity of aniline to the mouse.

Aniline Compounds↗

PubMed1994

The neurotropic activity of a structural analog of ACTH(5-7).

The tripeptide glutamyl-arginyl-proline (ERP) mimicking some structural features of the N-terminal fragment of adrenocorticotropic hormone, ACTH(5-7), has been synthesized. In contrast with ACTH fragments, ERP (0.015-0.15 mg/kg; intraperitoneal injection) hindered the formation of food-reinforced task in adult albino male rats. Besides, ERP caused a rapid inhibition of the previously formed conditioned task. Similar doses of ERP changed orientative-trying reaction and emotional behavior in rats in the 'open field' test. ERP at a dose of 0.15 mg/kg administered prior to the injection of 0.5 mg/kg ACTH(1-39) prevented increases in locomotor activity normally induced by this hormone. Thus, ERP disrupts learning, impairs performance of acquired task and blocks behavioral effects of ACTH and its fragments.

Adrenocorticotropic Hormone↗

PubMed1995

Effect of intra-peritoneal fludarabine on rat spinal cord tolerance to fractionated irradiation.

The effect of fludarabine (9-beta-D-arabinosyl-2-fluoroadenine-5'- monophosphate), an adenine nucleoside analogue, on the tolerance of the spinal cord to fractionated irradiation was studied in a rat model. Anesthetized female Fisher 344 rats received irradiation to 2 cm of the cervical spine with a telecobalt unit (dose rate 1.14 Gy/min). Radiation was administered in two, four or eight fractions spread over a 48-h period with or without fludarabine. Animals assigned to combined therapy received two daily intraperitoneal injections of fludarabine (150 mg/kg) given 3 h prior to the first daily radiation fraction. It was found that fludarabine reduced the iso-effect dose required to induce leg paresis at 9 months after irradiation for all fractionation schedules. Dose modification factors of 1.23, 1.29 and greater than 1.27 were obtained for two, four and eight fractions, respectively. Fitting the data with the direct analysis method of Thames et al. with an incomplete repair model [18] showed that the potentiating effect of fludarabine may be mediated through reduction in the number of 'tissue-rescuing units' (InK). Alpha and beta values were slightly but not significantly decreased, whereas the alpha/beta ratio was unchanged. These features suggest that fludarabine did not significantly inhibit cellular repair processes but rather reduced the spinal cord tolerance by a fixed additive toxic effect on the same target cells. In rodent models, the combination of fludarabine and fractionated radiation has previously been found to yield a therapeutic gain, i.e., the drug enhanced tumor response to a greater extent than it reduced normal tissue tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Differing responses of hamsters to infection by vesicular stomatitis virus Indiana and New Jersey serotypes.

Intraperitoneal injection of vesicular stomatitis virus, New Jersey serotype (VSV-NJ), into inbred LSH hamsters resulted in an inapparent infection and survival of the majority of the animals. Infectivity titrations of tissues from VSV-NJ-infected hamsters showed that little or no virus was present following infection. The few animals that died from VSV-NJ succumbed to neurological disease. This is in contrast to our previous work where we found that LSH hamsters are exquisitely sensitive to i.p. infection by VSV, Indiana serotype (VSV-IND), and that large amounts of VSV-IND could be detected in tissues. The 50% lethal doses of VSV-NJ and VSV-IND for LSH hamsters are approximately 10(7) pfu and 1 pfu, respectively. When peritoneal cells from LSH hamsters were infected in vitro with both VSV serotypes, the yields of VSV-NJ consistently were lower than yields of VSV-IND. The growth of the two serotypes in fibroblast and epithelial cell lines of hamster origin was similar. VSV-NJ was not more efficient than VSV-IND in inducing interferon in vitro or in vivo, and there appeared to be no difference in the sensitivities of the two serotypes to the antiviral activity of hamster interferon. Thus, i.p. infection with less than 10(7) pfu of VSV-NJ is avirulent for LSH hamsters and this avirulence may be due, in part, to partial intrinsic resistance of peritoneal macrophages to infection by VSV-NJ. When four LSH hamsters that had been immunized with VSV-NJ were challenged with 10(6) LD50 of VSV-IND, three of the four animals survived. Despite the fact that neutralizing antibodies to VSV-NJ did not cross-neutralize VSV-IND, five out of five LSH hamsters were protected by passive transfer of 1 ml of immune hamster anti-VSV-NJ antiserum prior to challenge with VSV-IND. This suggests an important role for non-neutralizing antibodies.

Animals↗

PubMed1992

Quantitation of preproenkephalin mRNA levels in brain regions from male Fischer rats following chronic cocaine treatment using a recently developed solution hybridization assay.

Quantitative solution hybridization assays were used to determine the picogram amounts of preproenkephalin mRNA (PPenk mRNA) and the microgram quanities of total rat RNA in extracts of eight brain regions from rats which had received three daily intraperitoneal injections of cocaine (10 or 30 mg/kg/day) or saline for 14 days. The young adult male Fischer rats were sacrificed 30 min after the final injection. The highest density of PPenk mRNA (pg PPenk mRNA/micrograms total cellular RNA) was found in extracts of striatum (34.08 +/- 1.79 pg/micrograms for 11 saline-treated rats), followed by extracts of nucleus accumbens (10.08 +/- 0.81 pg/micrograms), and extracts of hypothalamus (2.99 +/- 0.31 pg/micrograms). Extracts of frontal cortex (1.78 +/- 0.24 pg/micrograms), pituitary (1.39 +/- 0.08 pg/micrograms), central grey (1.31 +/- 0.16 pg/micrograms), and cerebellum (1.24 +/- 0.09 pg/micrograms) had intermediate values. Extracts of hippocampus (0.53 +/- 0.03 pg/micrograms) had the lowest density. No significant differences were found among the treatment groups in any brain area investigated. Therefore, chronic cocaine treatment as administered in this protocol did not alter expression of the gene encoding proenkephalin.

Animals↗

PubMed1995

Expression of interleukin 1 alpha, interleukin 1 beta and interleukin 1 receptor antagonist mRNA in mouse brain: regulation by bacterial lipopolysaccharide (LPS) treatment.

Lipopolysaccharide (LPS) stimulation is known to induce interleukin-1 (IL-1) mRNA expression in various immune cell types. Since IL-1 synthesis has been suggested to occur locally in brain tissue, we investigated the expression of IL-1 (alpha and beta) and IL-1 receptor antagonist (IL-1ra) mRNAs in various structures of the central nervous system, as well as in the spleen, following intraperitoneal injection of LPS (100 micrograms/mouse). After RNA extraction and amplification by the reverse transcription-polymerase chain reaction (RT-PCR), the PCR products were separated on an agarose gel, transferred and hybridized with digoxigenin-labeled probes synthetized by nested PCR. Glyceraldehyde phosphate deshydrogenase mRNA was used as an internal control. Under basal conditions the expression of IL-1 alpha, IL-1 beta and IL-1ra mRNAs in the brain was extremely low for the three cytokines; in the spleen these mRNAs were clearly detectable. Following LPS stimulation, mRNAs were strongly increased in all the tested tissues (cortex, hippocampus, hypothalamus, cerebellum, pituitary and spleen). The kinetics of mRNAs expressions in the brain were similar for all the tested regions, with a maximum at 6 h and a decrease up to 24 h after LPS administration. In the spleen the maximum was observed as soon as 1 h following stimulation. In conclusion, peripheral LPS stimulation induces a strong and transient expression of IL-1 alpha and IL-1 beta mRNAs in the brain. IL-1ra mRNA is also stimulated by LPS in various regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Acute plasma calcium regulation in rats: effect of vitamin D deficiency.

Vitamin D-replete (+D) and vitamin D-deficient (-D) rats received large doses of calcium (2-18 mg) by intraperitoneal injection and their responses to the calcium load was analysed in terms of the instantaneous and time-dependent responses of the plasma calcium concentration, [Cas]. Following an initial expansion, [Cas] returned to the preinjection value in a strictly exponential manner, with t1/2 = 22.5 +/- 2.0 (SE) min in +D and 51 +/- 5.2 min in -D animals. In both groups of animals, these rates were independent of the calcium load. Extraprolation of [Cas] to t = 0, i.e., the time just after administration of the calcium, revealed that the amount of calcium circulating at that moment was only about one-fifth of the amount that would have been found if all of the injected calcium had remained in the plasma. Calculations suggest that in all animals about four-fifths of the injected calcium load became distributed virtually instantaneously in the extracellular water. In both +D and -D groups the fraction of the injected load that left the plasma instantaneously was independent of the calcium load, of [Cas] at t = 0 or of the animals' plasma volume. The ability of rats to disperse some 80% of the load to outside the plasma would seem to constitute a major mechanism of acute plasma calcium regulation. Dilution was insufficient, however, totally to reduce [Cas] to the preinjection level. That occurred exponentially, with most of the calcium presumed to enter the skeleton. This exponential rate was markedly and significantly slower in the vitamin D-deficient animals than in their controls.

Animals↗

PubMed1987

Anorexia elicited by different catecholamines in rats.

Adrenaline (A) produces a strong anorexic effect, possibly by acting on hepatic receptors (nerve endings on hepatocytes). To study whether this is mediated by alpha- or beta-adrenergic mechanisms, or both, the anorexigenic effects of intraperitoneal injections of A, noradrenaline (NA) and isoproterenol (I) were studied under four different experimental conditions: (I) at the beginning of the dark period in rats fed ad libitum, or (II) on a 24 h-feeding/24 h-fasting schedule; (III) during the light period, under the same feeding schedule; (IV) after an acute 24 h fast. In condition I, the three catecholamines produced a marked decrease in feeding, slightly larger for A. In condition II (dark), they elicited a decrease in food intake about double that in condition III (light), their relative potencies also differed: A greater than I greater than NA in II and A greater than I = NA in III. In IV, the same relative potencies were obtained as in III. A mixture of half-doses of NA and I had the same effect in III and IV as either NA or I alone, suggesting that the alpha and beta effects are additive. However, even a mixture of the full doses of NA and I was not as effective as A in condition IV. This suggests that A is more potent than NA or I at stimulating hepatic adrenergic receptors that cannot be classified as either alpha or beta.

Animals↗