Multigeneration reproduction study of policosanol in rats

The objective of this study was to analyse the effects of isoflurane anesthesia (lasting for 15 or 60 min) and isoflurane anesthesia termination (after 1 or 24 h) on met-enkephalin (MENK) and leu-enkephalin (LENK) levels in discrete brain areas and spinal cord segments in rabbits. Moreover histochemical analysis of activities of succinate dehydrogenase, magnesium-dependent adenosine triphosphatase (Mg++ATP-ase) and acid phosphatase in the striatum and hypothalamus were carried out to evaluate the effects of isoflurane anesthesia on energetic, transport and catabolic processes. Throughout anesthesia (15 and 60 min) and after its termination (1 h) the LENK contents were increased in hypothalamus, hippocampus, mesencephalon and lumbar segment of spinal cord. Moreover, during isoflurane anesthesia and after its termination (1 h) MENK and LENK levels decreased in cervical segment and MENK content dropped in thoracic segment of spinal cord. Histochemical data indicated, that isoflurane enhanced energetic processes as well as exchange processes in neurocytes, glial cells, capillary walls and ependymal cells of the third ventricle. Measurements of acid phosphatase activity provided evidence of no signs of toxicity of isoflurane in the examined areas. The changes in enkephalin levels observed during the isoflurane anesthesia and after its termination depended on the type of examined neuropeptides, as well as on parts of the brain and spinal cord studied. The changes observed after isoflurane administration in enkephalinergic system are discussed with regard to our earlier experiments with halothane and enflurane.     

Evaluation of the developmental toxicity of methacrylonitrile in Sprague-Dawley rats and New Zealand white rabbits

Timed-pregnant Sprague-Dawley (CD) outbred rats and New Zealand White rabbits were dosed by gavage with methacrylonitrile (MACR) in distilled water during major organogenesis. Rats were dosed on Gestational Days (GD) 6 through 15 (0, 5, 25, or 50 mg MACR/kg/day) and rabbits on GD 6 through 19 (0, 1, 3, or 5 mg MACR/kg/day). Maternal clinical status was monitored daily during treatment. At termination (GD 20, rats; GD 30, rabbits), confirmed-pregnant females (25-26 per group, rats; 17-22 per group, rabbits) were evaluated for clinical status and gestational outcome; each live fetus was examined for external, visceral, and skeletal malformations. In rats, no treatment-related maternal clinical signs or mortality were observed, nor was there any adverse effect on maternal body weight or food or water consumption. At necropsy, absolute, relative, and adjusted maternal liver weight was increased at the mid- and high-dose groups, an effect that may be indicative of induction of hepatic enzymes rather than toxicity. In the absence of any indication of maternal toxicity, the no-observed-adverse-effect level (NOAEL) for maternal toxicity in this study was >/=50 mg MACR/kg/day. The NOAEL for developmental toxicity in rats was also >/=50 mg MACR/kg/day. There was no effect of treatment on postimplantation loss, mean fetal body weight per litter, or morphological development. In rabbits, maternal mortality and clinical signs were not dose related. Maternal food consumption, body weight, and liver weight were not adversely affected by treatment. Thus, the maternal NOAEL was >/=5 mg MACR/kg/day. Maternal toxicity, including death, was observed >/=7.5 mg/kg/day in preliminary studies. The developmental NOAEL was also >/=5 mg MACR/kg/day. There was no adverse effect of treatment on postimplantation loss or fetal body weight. A significant decrease in the percentage male fetuses per litter was observed, although there was no effect on total live litter size, suggesting that the reduction in the ratio of live male fetuses in the high-dose group was not biologically significant. MACR had no adverse effect on morphological development. In summary, oral administration of MACR to rats and rabbits during organogenesis, at doses that did not cause persistent maternal toxicity (50 mg MACR/kg/day, rats; 5 mg MACR/kg/day, rabbits), also did not cause any adverse developmental effects.     

Effect of age on protein conservation during very-low-energy diet in obese Sprague-Dawley rats

Perillyl alcohol is a monoterpene isolated from the essential oils of lavendin, peppermint, spearmint, cherries, celery seeds, and several other plants. In animal studies it has been shown to regress pancreatic, mammary, and liver tumors, to exhibit possible application as a chemopreventative agent for colon, skin, and lung cancer, and as a chemotherapeutic agent for neuroblastoma, and prostate and colon cancer. Perillyl alcohol is active in inducing apoptosis in tumor cells without affecting normal cells and can revert tumor cells back to a differentiated state. Its mechanism of action is unclear, but it has actions on various cellular substances which control cell growth and differentiation. It has been shown to increase mannose-6-phosphate/insulin-like growth factor II receptors, increase tissue growth factor beta receptors, increase Bak, decrease ras protein prenylation, decrease ubiquinone synthesis, and induce Phase I and Phase II detoxification systems. Preliminary human trials have not demonstrated tumor regression at a four times daily dosage schedule. In addition, significant side-effects, mainly gastrointestinal, have been experienced.     

Effect of dietary fats and sesamin on the lipid metabolism and immune function of Sprague-Dawley rats

We examined the effect of three dietary fats, safflower oil (SAF) rich in linoleic acid, borage oil (BOR) rich in gamma-linolenic acid, and perilla oil (PER) rich in alpha-linolenic acid, on the lipid metabolism, and chemical mediator and immunoglobulin levels in Sprague-Dawley rats, as well as the dietary effect of sesame-derived antioxidative sesamin. The serum cholesterol, phospholipid, triglyceride, prostaglandin E2 level and splenic leukotriene B4 level were lower in the rats fed on BOR or PER than in those fed on SAF. SES feeding suppressed the expression of the lipid-decreasing effect of BOR, but not in the rats fed on PER. In respect of the fatty acid composition of the liver and spleen, PER feeding gave a lower arachidonic acid level, and higher eicosapentaenoic and docosahexaenoic acid levels than SAF feeding did, while the effect of BOR feeding was marginal. The effect of SES feeding on fatty acid composition was much smaller than that of dietary fats. In respect of immunoglobulin production, PER + SES feeding gave the lowest IgE productivity in the mesenteric lymph node lymphocytes. These results suggest that PER feeding regulated lipid metabolism and exerted an anti-allergic effect by a different mechanism from that with BOR feeding.     

Disposition of butadiene epoxides in Sprague-Dawley rats

1,2-Epoxybutene (BMO) and diepoxybutane (BDE) are metabolic products of 1,3-butadiene in rodents. Both BMO and BDE are suspect in the development of tumors in rats and mice. To understand the distribution and elimination of these compounds in the absence of the rate-limiting production from butadiene, the pharmacokinetics of BMO and BDE in blood were determined in adult male Sprague-Dawley rats following intravenous administration. All animals were dually cannulated in these studies. For the BMO studies, rats were dosed with 71, 143, or 286 mumol/kg BMO (n = 3 for each dose group). For the BDE studies, rats were dosed with 523 mumol/kg BDE (n = 3). All animals tolerated the BMO and BDE doses without grossly observable adverse effects. Blood was drawn at predetermined time points and extracted in methylene chloride. BDE and BMO concentrations were quantitated by gas chromatography or gas chromatography/mass spectrometry. The BMO distribution half-lives were short and ranged from 1.4 min at the lowest dose to 1.8 min at the highest dose. Volume of distribution at steady state ranged from 0.53 +/- 0.17 to 0.59 +/- 0.31 l/kg. Systemic clearances ranged from 67 +/- 17 to 114 +/- 20 ml/min per kg. The terminal elimination half-lives were also short and ranged from 5.7 to 8.5 min among the doses. The pharmacokinetic parameters after an i.v. dose of 523 mumol/kg BDE were a distribution half-life of 2.7 min, terminal elimination T1/2 of 14 min, volume of distribution at steady state of 0.73 +/- 0.06 l/kg, and systemic clearance of 76 +/- 8 ml/min per kg. These pharmacokinetic parameters demonstrate the similarity between disposition of the two epoxides in rats, that include a rapid distribution after i.v. administration into a small extravascular body compartment as well as a rapid elimination from blood. These pharmacokinetic data provide useful blood clearance information for assessing the critical physiological and biochemical determinants underlying the disposition of butadiene epoxides.     

Effect of chronic captopril treatment on circulating and tissue renin-angiotensin system in SHR rats

This study investigated spectral differences in the phonation of vowels between a group of 21 children with velopharyngeal impairment and a paired control group of 42 subjects. The speech material was composed of the isolated vowels /a/, /i/, and /u/, a sustained vowel /a/, and four vowels included in spoken words: two nasals /in/ and /on/ in "dindon," and two orals /a/ and /o/ in "gateau." A bottom-up discriminant function analysis indicated that the cepstrum coefficients and the linear-FFT were the most efficient tools in the test to classify the set of children. They were superior to the results obtained with the formant-representation of the vowels. The use of a perceptive scale (barks) did not improve the results. Discrimination over the total group showed percentages lower than those obtained when boys and girls were assessed separately. The best discriminating results were obtained with the /a/ of "gateau" for the girls and with the isolated /i/ for the boys.     

Effects of ammonium dinitramide on preimplantation embryos in Sprague-Dawley rats

Ammonium dinitramide (ADN) is a class 1.1 oxidizer that may be used in rocket propellants and explosives. Previous studies have shown that ADN is a female reproductive toxicant, causing implantation failure in Sprague-Dawley rats when it is administered during the preimplantation period of gestation. The purpose of this follow-up study was to identify the mechanism(s) associated with implantation failure following exposure to ADN. Mated female rats were treated with 2.0 grams per liter (g l-1) ADN in their drinking water for 24, 48, 72, or 96 h before preimplantation embryos were harvested from the oviducts or uterine horns. On gestation day 1 (GD-1), comparable numbers of morphologically normal two-cell embryos were harvested from the oviducts of the treatment and control groups. On GD-2, the development of the embryos harvested from the treated animals was either slowed or halted when compared to the control embryos. By GD-4, 98% of the embryos harvested from the control group had developed to the morula or blastocyst stage; these were collected from the uterine horns. On GD-4 in the treated group, 41% of the harvested embryos remained at the two- to six-cell stage and 59% were degenerate; 82% of these embryos were collected from the oviducts. These data suggest that the implantation failure seen in animals treated with ADN is due to embryolethality.     

Metabolism of three cyclic nitrosamines in Sprague-Dawley rats

The metabolism of three cyclic nitrosamines has been studied in Sprague-Dawley rats. The compounds were nitrosopyrrolidine, nitrosohexamethyleneimine, and nitrosohepatamethyleneimine and were labeled at the alpha carbon with 14C. At low doses (2 to 4 mg/animal) the compounds were metabolized to 14CO2 to the extent of 77, 43, and 27%, respectively, after 24 hr. At doses closer to the 50% lethal dose of the compounds (70 to 160 mg/animal) the metabolism values were only 14, 4, and 8%, respectively, after 24 hr. The significance of these results is discussed.     

Case report on situs inversus totalis in two Sprague-Dawley rats

We macro- and microscopically examined two cases of congenital visceral transposition (situs inversus totalis) in SD rats. We also investigated the possibility of situs inversus in association with immotile-cilia syndrome. The rats had grown normally with no clinical signs of disease. Although all organs including the vascular system were located opposite to the normal position and displayed a mirror image on macroscopic observation, no abnormality was found in any of the organs on microscopic examination. Electron-microscopic observation revealed in neither animal any structural abnormalities of the cilia and flagella, which are one of the diagnostic characterizations of immotile-cilia syndrome. Congenital transposition of the viscera is rare and there are few reports examining complications with situs inversus in rats. This report will be helpful in accumulating information on this condition.     

Drinking water source and reproductive outcomes in Sprague-Dawley rats

As part of our work on the influence of water source on reproductive outcome, Sprague-Dawley rats were randomized to tap water, bottled water, or deionized water treatment groups, utilizing 160 animals per treatment; animals received the water prior to and during pregnancy. Rats were shipped in four batches (A-D). Batch effects were seen for several reproductive parameters. Because the tap water supply was interrupted by an earthquake resulting in an unbalanced design, primary analyses utilized only batches C and D, which included most of the tap water-treated rats. A treatment effect with respect to resorption frequency was seen that was marginally significant using a fixed-effects analysis of variance (P = 0.053), but not when batch was entered as a random effect (P = 0.36). The data were modeled by logistic regression, controlling for batch, litter size, and batch-treatment interaction. The odds ratio comparing tap to bottled water was 1.8 (95% CI 1.0 to 3.3, P = 0.05), which was similar to the epidemiologic result that prompted this study. The magnitude of this association varied by batch, and the difference in resorption frequency was within the range of variation seen for control animals. Although these findings do not justify public health action at this time, further investigation is warranted.     

Effect of interleukin-8 and monocyte chemotactic protein-1 on adhesion of circulating granulocytes and monocytes from asthma patients to human venous endothelial cells

Four mouse vomeronasal receptors (mV1Rs) have been isolated by similarity to rat vomeronasal receptor (V1R) motifs. The four mV1Rs identified in this study are members of two distinct subfamilies. Specific in situ hybridization probes (ISH) derived from the 3' non-coding regions of the mV1R genes, were used to detect expression of a single receptor and probes from the homologous coding regions were used to detect expression of subfamily members. The ISH results showed that the mV1Rs expressing neurons were scattered in the middle/upper layer of the vomeronasal organ (VNO) sensory epithelium in serial VNO sections but were excluded from the deeper layers of the VNO sensory epithelium and these neurons were found to co-express the mRNA for the G-protein Galphai2, and were distinct from the deeper layers of the VNO sensory epithelium where the mRNA for Galphao positive neurons was located.     

Effect of dexamethasone on endothelial nitric oxide synthase in experimental congenital diaphragmatic hernia

AIMS: To study the effect of prenatal glucocorticoid treatment on endothelial nitric oxide synthase (eNOS) expression in rats with congenital diaphragmatic hernia (CDH). METHODS: CDH was induced in fetal rats by the maternal administration of nitrofen on day 9.5 of gestation. Dexamethasone was administered on days 18.5 and 19.5 before delivery of the fetuses on days 20.5 and 21.5. Pulmonary eNOS protein expression was studied by western immunoblotting and immunohistochemistry. RESULTS: On day 20.5, eNOS expression was significantly reduced in CDH pups compared with normal control rats. Dexamethasone treated CDH pups had eNOS concentrations equivalent to those of normal animals. By day 21.5, however, there was no detectable difference in eNOS expression between the experimental groups. CONCLUSIONS: eNOS is deficient in near term (day 20.5) CDH rats. Dexamethasone restores eNOS expression in these animals to that seen in normal rat lungs. At term, the precise role of eNOS in the pathophysiology of CDH remains uncertain.     

Prenatal exposure to cocaine: effects on aggression in Sprague-Dawley rats

Social/aggressive behavior in adult rat offspring (beginning at postnatal Day 180) prenatally exposed to saline, cocaine, or amfonelic acid (AFA) was examined. Pregnant rats received injections of 15 mg/kg of cocaine, or 0.9% saline twice daily, s.c., or on 2 consecutive days at 4-day intervals, or 1.5 mg/kg amfonelic acid daily throughout gestational Days 1-20. Frequency, duration, and latency of 11 social/aggressive behaviors were recorded for two 15-min sessions during which a smaller male intruder replaced an ovariectomized female in the resident's home cage. Subjects received a s.c. saline injection before Session 1 and 2.0 mg/kg of gepirone, a 5HT1a partial agonist, prior to Session 2. Prenatal cocaine treatment resulted in alterations of aggressive behavior. Aggressive behavior was reduced by gepirone in all groups but to a lesser extent in the AFA group.     

Catechol O-methyltransferase inhibitor tolcapone has minor influence on performance in experimental memory models in rats

DNA-based immunization is a promising new technique for generating antibodies in laboratory animals for diagnostic purposes in biological science. The main advantages are the elimination of time and labor and the technically demanding steps of antigen purification. The DNA sequence of the protein of interest, cloned in a suitable in vivo expression vector that is administered intramuscularly or intradermally, is sufficient to induce an immune response in animals. We report the induction of antibodies to tobacco mosaic virus (TMV) coat protein (CP) as a highly immunogenic structural protein and potato virus Y (PVY) P1 protein (P1) as a nonstructural protein. The appropriate nucleotide sequences were introduced in a mammalian expression vector (pSG5) and injected intramuscularly into New Zealand White rabbits (Oryctolagus cuniculus). By 10 days post-injection (dpi) a specific immune response was detected against TMV-CP, while it took about 5 weeks for a response to PVY P1. In both cases the antibody titers were significantly above the corresponding pre-immune serum, however, they were considerably below the titer of the matching conventionally produced antiserum. To our knowledge, this is the first report of DNA-based immunization in order to generate antibodies to plant viral proteins, but further improvements are necessary to increase antibody titers before this promising new technique can be introduced broadly in plant science for diagnostic purposes.     

Effect of castration and testosterone in experimental models of depression in mice.

In the behavioral despair (forced swimming) test and in the tail-suspension test, long-term (30–32 days) castration significantly increased the duration of immobility in mice. Testosterone propionate (1 or 10 mg/kg/day–2 sc for 4 days), although not affecting the duration of immobility in sham-operated mice, reduced the duration of immobility in castrated mice to within normal limits. Desipramine (20 mg/kg ip) decreased the duration of immobility both in sham-operated and in castrated animals. These results indicate that castration favors an inactive behavior and that testosterone, although having no "antidepressant" effect per se, is necessary for the male animal to cope normally with adverse environmental situations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Circulating lipophages and aortic foam cells in experimental atherosclerosis of rabbits under altered reticuloendothelial activity

Administration of Freund's adjuvant to cholesterol-fed rabbits inhibited the induction of atheroma in the aorta of rabbits when compared with cholesterol-fed indiaink-treated animals and cholesterol-fed saline-treated controls. Simultanously the blockade of the reticuloendothelial system by india ink caused a greater degree of atheromatous lesions in these rabbits. Smears of peripheral blood studied by light microscopy revealed the presence of circulating lipophages which were morphologically similar to the aortic foam cells isolated from the same animal. Isolation of mononuclear lipid-containing foam cells from aortic intima and the presence of a morphologically similar type of cell in circulating blood indicate that the blood might be the most likely source of intimal foam cells.     

THC-induced place and taste aversions in Lewis and Sprague-Dawley rats.

The hedonic properties of delta-9-tetrahydrocannabinol (THC) were assessed in place and taste conditioning paradigms in both Lewis and Sprague-Dawley rat strains. THC produced place avoidance, taste avoidance, and aversive taste reactivity responses in both strains. The Lewis strain displayed more aversive taste reactions and a stronger taste avoidance when conditioned with lower doses of THC than did the Sprague-Dawley strain of rats. THC is an anomalous drug of abuse that appears to be aversive to rats when assessed by these measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of xiao chaihu decoction on experimental alkaline reflux gastritis in rats

The effects of Xiao Chaihu Decoction (XCHD) on alkaline reflux gastritis and gastric secretion in rats was observed. Results: (1) 5g/kg, 20 g/kg of XCHD might markedly inhibit the gastric lesion induced by gastric feeding of sodium taurocholate; (2) 5g/kg, 20g/kg of XCHD might significantly prevent the gastric lesion induced by gastric feeding of intestinal juice; (3) On chronic reflux gastritis model induced by spring-expanded pylorus after 4 or 8 weeks, 4g/kg-20g/kg of XCHD might lower the incidence of gastritis, and reduce the intragastric bile acid; (4) 5g/kg and 20g/kg of XCHD might significantly inhibit the secretion of gastric juice and acid as well as the activity of pepsin. The results suggested that XCHD had anti-reflux gastritis effect.     

Effects of dietary acetate and bicarbonate on experimental atherosclerosis in rabbits

Scanning electron microscopic evaluation of the resected plaques from 11 patients with symptomatic and asymptomatic lesions of the carotid artery bifurcation were carried out. The most common findings were mounds of atheromatous material, many of which appeared to be fractured and capped with fibrin-platelet exudates, projecting into the lumen of the vessels. Both small and large ulcer craters were identified, and attached bodies were present in three-fourths of the specimens studied. These consisted most commonly of platelet clumps and fibrin sheets and were intimately related to the atheroma.