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Micronucleus test with vincristine administered by intraperitoneal injection and oral gavage.

The effects of vincristine sulfate (VINC) on micronucleus induction were studied in 2 strains of mice (MS/Ae: CD-1) following intraperitoneal (i.p.) or oral administration (p.o.) of the chemical. On the basis of a small-scale acute toxicity study and a pilot micronucleus experiment, the full-scale micronucleus test was performed with a sampling time of 24 h at doses of 0.063, 0.125, 0.25 and 0.5 mg/kg (i.p.) and 1.25, 2.5, 5.0 and 10 mg/kg (p.o.). The maximum frequency of micronucleated polychromatic erythrocytes was 7.15% in MS/Ae mice and 4.98% in CD-1 mice at 5.0 mg/kg p.o. in both cases. The maximum frequencies by the i.p. route (9.93% in MS/Ae mice; 11.68% in CD-1 mice) occurred at 0.25 mg/kg and 0.125 mg/kg, respectively. Although the doses showing a positive response were different between the 2 routes, VINC induced micronuclei very efficiently at all doses tested by both administration routes in both strains.

Administration, Oral↗

Distribution of 2-ethylhexanoic acid in mice and rats after an intraperitoneal injection.

The distribution of 2-ethylhexanoic acid (2-EHA), a new wood preservative agent was studied in mice and rats. 2-14C-EHA in rat blood, brain, liver and kidney was quantitated by liquid scintillation analysis and by wholebody autoradiography in mice. A single intraperitoneal dose of 2-14C-EHA was injected in both species. Animals were sacrificed 30 min., 2 and 6 hr after the administration of 2-14C-EHA in autoradiography experiments. The highest uptake of 2-14C-EHA was observed in the liver, kidney and blood of mice. In contrast, low uptake of 2-14C-EHA was seen in the brain. 2-14C-EHA was well detectable in the olfactory bulb and in the salivary gland. In rats, at 2 hr after administration the highest concentration of 2-14C-EHA occurred in blood (0.3% of the total dose/g tissue). The radioactivity in the liver (0.2%) and kidney (0.1%) was also relatively high. The concentration of 2-14C-EHA was low in the brain (0.02%). By 6 hr. the radioactivity had decreased rapidly and was hardly measurable at 24 hr after the administration. The results suggest that 2-EHA is rapidly cleared from the tissues.

Animals↗

An antinociceptive effect of the intraperitoneal injection of nifedipine in rats, measured by tail-flick test.

The tail-flick (TF) technique was used to assess the antinociceptive properties of nifedipine (NIF) given intraperitoneally (i.p.). First, the most suitable intensity of the noxious stimulus (temperature of the bulb) has been ascertained and used in the main study. Male Sprague-Dawley rats received NIF, dissolved in dimethyl sulfoxide (DMSO) at the doses of 0.0, 0.5, 2, 5, 10 and 15 mg/kg, or control with no injection. For the main study, the noxious stimulus was limited to 15 sec (cut-off time) and TF latencies were recorded up to 120 min. The antinociceptive response was expressed as the area under the curve for each rat and analyzed by one-way ANOVA. The antinociceptive response to the lower doses of NIF (0.5 and 2 mg/kg) did not differ from control (no injection) and DMSO alone. Significance was found at 5, 10 and 15 mg NIF with no difference among the doses. However, there was an increasing tendency of the mean values from 0.5 to 15 mg NIF resulting in a positive correlation. The correlation coefficient was 0.32483 (p = 0.015) and regression equation Y = (19.37) x dose + 1320. Our data suggest that spinal mechanisms are involved in NIF-induced antinociception.

Analgesics↗

The effect of naloxone on sexual behavior in female rats depends on the site of injection.

Intraperitoneal injections of the opiate receptor antagonist naloxone (0.1, 1, 5 or 10 mg) had no effects on sexual behavior in ovariectomized female rats made either partially or fully receptive by injections of ovarian hormones. Intracerebroventricular (i.c.v.) injections of naloxone (10, 50 or 100 micrograms) had no effects on the behavior of partially receptive rats and in fully receptive rats an i.c.v. injection of a high dose of naloxone (100 micrograms) inhibited the behavior. Intrathecal (i.t.) injections of naloxone (50 or 100 micrograms) facilitated sexual behavior in partially receptive rats while i.t. injections of even very high doses of naloxone (500 micrograms) had no behavioral effects in fully receptive rats. Thus, the effects of naloxone on female sexual behavior depend on the site of injection.

Animals↗

Transport of Eimeria necatrix sporozoites in the chicken: effects of irritants injected intraperitoneally.

Light and electron microscopic observations confirmed that Eimeria necatrix sporozoites first enter villous epithelial cells of the chicken small intestine and are transported to the crypts by mononuclear cells. Ultrastructurally, these cells resemble granulated intraepithelial lymphocytes (IEL) rather than macrophages, as suggested previously. The injection of chickens intraperitoneally (i.p.) with a variety of irritants, including proteose peptone, at the time of oocyst inoculation or up to 12 hr postinoculation (PI) resulted in a delay in the arrival of sporozoites at the crypt. Significantly fewer sporozoites had arrived at the crypt by 24 hr PI in i.p.-injected birds as compared to controls. This delay in the arrival of sporozoites at the crypts was reflected by a delay in the development of intestinal lesions and in peak oocyst production. However, there was no significant decrease in the total numbers of oocysts produced by these birds as compared to controls, indicating that no significant loss of sporozoites occurs during the possible rerouting of the parasites. The presence of infective stages in extraintestinal sites was detected by transferring various tissues to coccidia-free recipients. Infection was transferable by gut, liver, and spleen from irritant-injected and control birds at all time intervals studied (12, 24, 36, and 48 hr PI). Infection was also transferable with blood and kidney, but not consistently. A small number of oocysts was passed by the recipients of peritoneal wash from irritant-injected birds at 12 hr PI. In all transfers, the prepatent period was normal, suggesting that the migrant stages are sporozoites.

Animals↗

Biodistribution and pharmacokinetics of 111In-dTPA-labelled pegylated liposomes after intraperitoneal injection.

The biodistribution and pharmacokinetics of 111In-DTPA-labelled pegylated liposomes (IDLPL) and unencapsulated 111In-DTPA administered by the intraperitoneal (i.p.) and i.v. routes in non-tumour-bearing mice were compared. Mice received i.p. or i.v. injections of 0.37 MBq 111In-DTPA either encapsulated in liposomes or as an unencapsulated agent. A variety of tissues were dissected from 5 min to 192 h to determine the biodistribution and pharmacokinetics. Injection of IDLPL via the i.p. route caused a 74-fold increase in the area under the concentration (AUC) versus time curve in the peritoneum compared to unencapsulated 111In-DTPA. Similarly, the AUC for all the intra-abdominal tissues was increased significantly (20-427-fold). When i.p. IDLPLs were compared directly with i.v. IDLPLs, more modest changes were seen. There were increases in AUC for peritoneum (1.4-fold), ovary (1.3-fold), stomach (2.9-fold), pancreas (3.6-fold). small intestine (1.5-fold). colon (1.2-fold), gallbladder (5.1-fold) and adrenal gland (2.1-fold). These data support the development of i.p. liposomal chemotherapy for the treatment of intraperitoneal malignant disease.

Adrenal Glands↗

Effects of concentration of ethanol injected intraperitoneally on taste aversion, body temperature, and activity.

Levels of ethanol-induced conditioned taste aversion and hypothermia were found to be directly related to the concentration of fixed amounts of ethanol injected i.p. in a range of doses (1.0--1.8 g/kg) and concentrations (8--32% v/v) commonly used in behavioral studies. No effect of ethanol concentration on locomotor activity was obtained. The results of blood-ethanol determinations indicate that a given dose of ethanol is absorbed more rapidly, and thus reaches greater peak levels, when injected in a higher concentration. Thus ethanol dosage might be better manipulated by varying the volume of a single concentration rather than by altering concentration. In this way, dose-response data will not be obscured by concentration-induced differences in absorption.

Animals↗

Alterations of intestinal and renal functions in rats after intraperitoneal injections of lead acetate.

When lead acetate was administered intraperitoneally to young rats at a dose of 20 mg/kg (five times a week for 6 weeks), their growth rate was retarded when compared with controls injected with sodium acetate. Only a small amount of the heavy metal reached the circulation and exerted limited effects on typical target organs. However, large, electron-dense inclusion bodies were found in the abdominal cavity. The in vivo intestinal absorption of glucose was reduced. When perfused at 40 mM concentration, the experimental animals had a mean absorption rate of 152.1 nmol/min . cm vs. 230.6 in the controls (p less than 0.01). Also, sodium and potassium transport was reduced. No effects were observed on amino acid transport and (Na+-K+)-ATPase. Mg++-ATPase, glucose-6-phosphatase, fructose-1, 6-diphosphatase, pyruvate kinase, succinic dehydrogenase, and tryptophan hydroxylase in the small intestinal mucosa and the kidney were unaltered. Renal alkaline phosphatase was decreased. These studies confirm the greater susceptibility of some active transport mechanisms of the small intestinal mucosa to lead toxicity, compared to those of the kidney.

Amino Acids↗

Mature helper T cell requirement for immunoglobulin production by neonatal native B cells injected intraperitoneally into severe combined immunodeficient (SCID) mice.

It is accepted that human neonatal naive B cells produce mainly IgM in vivo as well as in vitro. Our previous work has demonstrated that i.p. injection of neonatal B cells together with adult mature T cells induces substantial levels of human IgG in the serum of SCID recipient mice. The present study was further attempted to determine the cellular components required for immunoglobulin production by neonatal B cells in SCID mice. When neonatal B and adult T cells were transferred into the SCID mice, human immunoglobulins, largely of IgG, were maximally detected in the serum around 6 weeks after a cell transfer. Depletion of CD4+ T cells from adult T cells resulted in undetectable levels of human immunoglobulin in the serum. By contrast, CD4+ T cell-enriched populations exhibited an enhancing effect on immunoglobulin production by neonatal B cells. Higher levels of immunoglobulin, including IgA and IgM, were detected in the peritoneal fluid than in the serum as early as 2 weeks after the cell transfer. Human T cells expressing activation antigens such as CD45RO and HLA-DR antigens were identified in the peritoneal lavages. These results suggest that neonatal naive B cells are able to differentiate into cells producing all classes of immunoglobulin in the presence of mature CD4+ T cells in a SCID mouse environment. The peritoneal cavity of SCID mice appears to provide a suitable place for immune responses by human cells, possibly in association with a certain xenogeneic reaction.

Adult↗

Induction of pulmonary indoleamine 2,3-dioxygenase by intraperitoneal injection of bacterial lipopolysaccharide.

Indoleamine 2,3-dioxygenase [indoleamine: oxygen 2,3-oxidoreductase (decyclizing)] activity in the supernatant fraction (30,000 X g, 30 min) of the mice lung homogenate increased approximately 30- to 50-fold after an intraperitoneal administration of bacterial lipopolysaccharide. In all other tissues tested, no significant increase in enzyme activity was observed. The effect appeared to be specific for the lipopolysaccharide fraction because glycogen and zymosan were almost ineffective under the same experimental conditions. In the lung, the enzyme activity increased almost linearly during the first 24 hr after a single injection of the lipopolysaccharide fraction (20 microgram per mouse). The enzyme activity started to decrease after 48 hr and reached a normal value after about 6 days. The increase in enzyme activity was completely abolished by cycloheximide or actinomycin D. Other enzymes in the lung such as beta-glucuronidase, acid phosphatase, and monoamine oxidase did not change significantly with this treatment.

Animals↗

Micronucleus test with benzo[a]pyrene using a single peroral administration and intraperitoneal injection in males of the MS/Ae and CD-1 mouse strains.

The effect of route of administration on the outcome of the micronucleus test was examined by administering benzo[a]pyrene (B[a]P) perorally (p.o.) and intraperitoneally (i.p.) to males of the MS/Ae and CD-1 mouse strains. This study consisted of 3 parts. First, an acute toxicity study lasting 3 days was done to estimate LD50s. The LD50 was larger than 1600 mg/kg for both routes in the 2 strains. Second, pilot micronucleus tests were carried out, on the basis of which an appropriate sampling time (48 h) and dose levels (62.5, 125, 250, and 500 mg/kg) were chosen for both routes and both strains. Third, full-scale micronucleus tests were done, which indicated that (1) B[a]P induced micronuclei dose-dependently by each administration route in each strain, (2) the i.p. route induced frequencies of micronuclei almost equal to or slightly higher than did the p.o. route, and (3) the MS/Ae strain was the higher responder.

Administration, Oral↗

"Slimy eyes phenomenon" in mice intraperitoneally injected with Pseudomonas aeruginosa cells or cell products.

Mice intraperitoneally treated with various Pseudomonas aeruginosa products or lipopolysaccharides of some selected Enterobacteriaceae representatives were found also to react by an increased slime secretion of the eye conjunctivae. The condition, tentatively designated as "Slimy Eyes Phenomenon", started to develop shortly post-treatment, culminated within 24-48 h when the eyes became fully glued up with slime, and receded 48-72 h later, leaving no sequelae for the eye or the general condition of the animal. No such phenomenon has to date been observed in other laboratory animal species.

Animals↗