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PubMed1994

Differences in the kinetic properties, effect of calcium and sensitivity to inhibitors of paraoxon hydrolase activity in rat plasma and microsomal fraction from rat liver.

The properties of a rat hepatic microsomal enzyme that hydrolyses O,O-diethyl-p-nitrophenylphosphate (paraoxon) were studied and compared to the paraoxon hydrolase activity found in rat plasma. The pH stability for both enzyme activities was optimum between pH 6.0 and 9.0. An overall analysis of the data showed that the microsomal fraction was less resistant to the effect of the pH than plasma. The kinetic constants for heat inactivation evaluated for paraoxonase in rat plasma and liver microsomal fraction indicate that paraoxonase tends to inactivate faster in rat liver microsomes than in rat plasma. The apparent activation energies of the heat inactivation process were 77.7 and 61.1 kcal/mol for rat plasma and microsomal fraction, respectively. Enzyme activity was lost after both dialysis and incubation with EDTA and partially restored by the addition of calcium. In rat plasma samples the requirement for calcium was absolute (essential activator) while in the microsomal fraction the reaction may occur, to a minimum extent, in the absence of the activator (non-essential activator). Calcium restored 85% activity when added immediately after EDTA; restored activity decreased when the time interval between addition of EDTA and calcium was increased. Other metals were not able to restore activity previously inhibited by EDTA or dialysis. The response to several inhibitors (EDTA, Mn, Co, Zn, Ba, Mg, Cu, La, Hg and p-hydroxy-mercuribenzoate) of rat plasma and microsomal fraction was studied, determining the type of inhibition and the inhibition constants. Plasma enzyme was always more resistant than liver sample to the effect of the inhibitors and showed different types of inhibition than the liver microsomal fraction. In general we found more differences than analogies between the rat plasma and liver enzyme which suggests the presence of two enzymes or two different forms of the same enzyme. Furthermore the existence of an EDTA-resistant fraction in rat liver microsomes suggests that more than one enzyme capable of hydrolysing paraoxon is present in the microsomal fraction of rat liver.

Animals↗

PubMed1988

The effects of ageing on vascular alpha-adrenoceptors in pithed rat and rat aorta.

In the pithed rat preparation in the absence of captopril, the pressor potency of the alpha 2-adrenoceptor agonist xylazine was significantly reduced in 24 month old rats. This difference between young (3-6 month) and old rats in xylazine potency was eliminated by captopril (5 mg kg-1), which caused a greater shift in xylazine potency in young than in old rats. In the rat isolated aorta, the contractile potency both of the alpha 1-adrenoceptor agonist phenylephrine and of 5-hydroxytryptamine were significantly reduced in 24 month old rats. Hence, both in pithed rats and in the rat isolated aorta, the contractile potency of alpha-adrenoceptor agonists is reduced in aged rats, but the altered responsiveness is not at the level of the alpha-adrenoceptor. In the pithed rat, alpha 2-adrenoceptor responsiveness is reduced with ageing probably due to decreased levels of angiotensin II, and in the rat aorta alpha 1-adrenoceptor responsiveness is reduced with ageing, but since responsiveness to 5-HT is also reduced, this may be a post-receptor change in responsiveness.

Adrenergic alpha-Agonists↗

PubMed1987

Analysis of the interaction between rat immunoglobulin E and rat mast cells using anti-peptide antibodies.

Polyclonal antisera with pre-determined specificities for a range of rat IgE epitopes were produced by immunizing rabbits with KLH-conjugates of five different synthetic peptides representing sequences 378-396, 414-428, 491-503, 522-535 and 560-571 in the CH3 and CH4 domains of rat IgE. Each rabbit elicited peptide-specific antibodies which were capable of binding affinity-purified rat IgE (IR162) (titres 1/1000-1/10,000) and IgE in rat immunocytoma serum (IR162) either immobilized on microtitre-plates or in free-solution as assessed by ELISA. Heating a solution of rat IgE at 56 degrees C for 1 hr, a treatment known to abolish the cytophilic activity of rat IgE and also induce irreversible conformational changes in the CH3 and CH4 domains, resulted in enhanced binding of the immunoglobulin to antibodies directed against IgE sequences represented by two of the synthetic peptides 414-428 and 491-503, but not to the three other peptides. The five anti-peptide sera together with two previously studied antisera specific for rat IgE sequences 459-472 and 542-557 were tested in functional assays designed to investigate the mode of interaction between rat IgE and its receptor on rat mast cells. Each anti-peptide serum was capable of inhibiting the binding of IgE to mast cells and furthermore, able to initiate the secretion of histamine from cells sensitized with rat IgE in an "anti-IgE"-induced manner. In view of the evidence implicating the CH3 and/or CH4 domains as the location of the mast cell receptor-site on rat IgE, we propose a model to describe the mode of interaction between IgE and its mast cell receptor.

Amino Acids↗

PubMed2002

Rats can track odors, other rats, and themselves: implications for the study of spatial behavior.

In order to demonstrate that rats solve dead reckoning (path integration) tasks in which they return to a starting location using self-movement (idiothetic) cues, it is necessary to remove external (allothetic) cues. Odor cues, especially those generated by a rat on a single passage, are difficult to control and they can potentially serve as a cue to guide a homeward trip. Because it is presently unknown whether rats can track the cues that they themselves leave, as opposed to the odor trails left by other rats, we investigated this question in the present study. A tracking task was used in which rats: (1) followed a scented string from a refuge to obtain a food pellet located on a large circular table; (2) followed odors left on the table; (3) followed odors left by the passage of another rat; or (4) followed odors left by themselves. Groups of rats were presented with strings scented with either the rat's own odor (Group Own), a conspecific's odor (Group Other), or another scent, vanilla (Group Vanilla). After training, a series of discrimination tests were given to determine the nature of the stimulus that controls scent tracking. The results indicated that Own, Other, and Vanilla groups were equally proficient in discriminating and following their respective odors. The rats were also able to follow odor trails on the table surface as well as a trail left by the single passage of another rat or their own passage. This is the first study to demonstrate that rats can discriminate between conspecific odors and their own odor left during a single passage. The results are discussed in relation to their implications for experimental methodology and olfactory contributions to spatial navigation in general and dead reckoning in particular.

Animals↗

PubMed2003

Role of c-kit receptor tyrosine kinase-mediated signal transduction in proliferation of bile epithelial cells in young rats after ligation of bile duct: a study using Ws/Ws c-kit mutant rats.

BACKGROUND/AIMS: Recently, it has been shown that the c-kit receptor tyrosine kinase (KIT) is expressed in the liver of young rats, and its expression is up-regulated in bile epithelial cells (BEC) after ligation of the common bile duct (BDL). To clarify a role of KIT in BEC, we examined whether BEC of Ws/Ws rats, whose KIT kinase activity was severely impaired, could proliferate in response to bile stasis after BDL. METHODS/RESULTS: When 2-week-old control normal (+/+) and Ws/Ws mutant rats underwent BDL, only a few BEC were found in the portal field of livers of Ws/Ws rats, whereas many BEC were found in that of +/+ rats. Furthermore, Ki-67 immunostaining showed that the proliferative activity of BEC in 2-week-old Ws/Ws rats was much lower than that in +/+ rats of the same age. In contrast, when 6-week-old +/+ and Ws/Ws rats underwent BDL, BEC similarly proliferated in the livers of +/+ and Ws/Ws rats, and the proliferative activity of BEC was comparable. CONCLUSIONS: The mechanism whereby BEC proliferate in response to bile stasis after BDL may be different between 2- and 6-week-old rats, and KIT mediated-signal transduction plays a crucial role in the proliferation of immature BEC in young rats.

Age Factors↗

PubMed2006

Increased platelet aggregation in vivo in the Zucker Diabetic Fatty rat: differences from the streptozotocin diabetic rat.

BACKGROUND AND PURPOSE: Diabetes mellitus, especially type 2, is associated with increased arterial thrombosis. Our aims were (i) to characterize and compare platelet aggregation in vivo and in vitro in a type 2 diabetes model; and (ii) to determine whether these results differ from those in a type 1 diabetes model. EXPERIMENTAL APPROACH: Platelet aggregation to ADP in lean or obese Zucker Diabetic Fatty (ZDF) rats and in streptozotocin (STZ)-treated or control Wistar rats was measured in vitro, using Born aggregometry, and in vivo, by (111)Indium-labelled pulmonary platelet accumulation. KEY RESULTS: In vivo, ADP responses were higher in obese (type 2 model) than lean ZDF rats. However, in vitro, ADP aggregation did not differ between platelet-rich plasma from ZDF lean or obese rats; nor was any difference seen in ADP responses when platelets from either lean or obese ZDF rats were suspended in plasma from obese or lean ZDF rats, respectively. In vivo, ADP responses were similar in STZ treated (type 1 model) and control rats whereas, in vitro, isolated platelets from STZ diabetic rats were more responsive to ADP aggregation than controls. Platelets from control or STZ-treated rats suspended in plasma from STZ-treated rats exhibited reduced ADP aggregation, compared to when suspended in plasma from control rats. CONCLUSIONS AND IMPLICATIONS: The platelet aggregation results obtained in vitro do not reflect those in vivo, therefore in vitro aggregation data should be interpreted with caution. Moreover, both in vitro and in vivo, different diabetic models exhibit important differences in platelet responsiveness.

Animals↗

PubMed1998

Molecular cloning and functional analysis of cDNA encoding a rat leukemia inhibitory factor: towards generation of pluripotent rat embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo. Maintenance of the stem-cell phenotype of ES cells in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) such as leukemia inhibitory factor (LIF). Here we report the cloning of complete rat LIF cDNA and its nucleotide sequence so as to facilitate studies of rat ES cell technologies on tumor biology. The nucleotide sequence of the rat LIF cDNA indicated that the rat LIF has 91% amino acid sequence identity with murine LIF. The cloned rat LIF cDNA has a putative biological activity as a differentiation-inducing factor on the murine myeloid leukemia cell line M1 cells. Culture supernatant of the rat LIF cDNA-transduced rat fibroblast cell line could maintain the stem-cell phenotype of rat ES cells which showed alkaline phosphatase activity, and this effect was much stronger than that by murine LIF. The availability of rat LIF which shows DIA will assist the in vitro analysis of rat ES cells, and culture of these cells is a route for the generation of gene targeting in rat.

Amino Acid Sequence↗

PubMed2001

Photoresponsive Fischer 344 Rats are reproductively inhibited by melatonin and differ in 2-[125I] lodomelatonin binding from nonphotoresponsive Sprague-Dawley rats.

Many temperate-zone species use photoperiod as an environmental cue to regulate reproductive timing. Strains of laboratory rats differ in their responsiveness to photoperiod, with the Fischer 344 (F344) strain being the most responsive known. F344 rats and closely related strains that differ in photoresponsiveness may be useful models to study the mechanisms and genetic basis for photoresponsiveness. We tested two hypotheses: (i) that melatonin mediates photoresponsiveness in F344 rats, as is the case in all other mammals tested, and (ii) that the location, abundance, or affinity of melatonin receptors, as estimated by the amount and location of binding of the radioligand 2-[125I]-iodomelatonin (IMEL) in the brain, might cause variation in photoresponsiveness among rat strains. Melatonin injections 1 h before lights off in a stimulatory photoperiod (L14 : D10) induced reproductive inhibition and reduced weight gain in a manner similar to short days of L8 : D16, while injections of ethanolic saline vehicle did not. Interestingly, melatonin injections administered during an inhibitory photoperiod (L10 : D14) caused greater inhibition of both reproduction and weight gain than short photoperiod alone. Pinealectomized F344 rats implanted subcutaneously with melatonin in a silastic capsule did not differ in testis size or body weight from controls with blank implants. The brains and pars tuberalis of the pituitary from photoresponsive F344 rats and nonphotoresponsive Harlan Sprague-Dawley (HSD) rats were processed for autoradiography using IMEL. We found significantly higher specific IMEL binding in the anterior and posterior regions of the paraventricular nucleus of the thalamus (PVNt) and reuniens nucleus of the thalamus of F344 rats than in the same areas in HSD rats. There were no differences between strains in specific IMEL binding in the medial PVNt, anteroventral and anterodorsal nucleus of the thalamus, suprachiasmatic nucleus, or the pars tuberalis. These results indicate that melatonin mediates photoresponsiveness in F344 rats. In addition, they provide support for the hypothesis that F344 rats may be photoresponsive due to differences from other strains in the location, density, or affinity of melatonin receptors.

Animals↗

PubMed2003

Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation.

The presence of cannabinoid1 (CB1) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl-2-choroethylamide (ACEA; 10 and 30 micro g in 50 micro L), a selective CB1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 micro g in 50 micro L) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 +/- 4% of control; P < 0.01) and inflamed (12 +/- 8% of control; P < 0.05) rats. Similarly, noxious (80 g) mechanically evoked responses of spinal neurons were inhibited by peripheral injection of ACEA (30 micro g in 50 micro L) in noninflamed rats (51 +/- 9% of control; P < 0.01) and rats with peripheral carrageenan inflammation (21 +/- 8% of control; P < 0.01). Inhibitory effects of ACEA were significantly greater in rats with peripheral carrageenan inflammation than in noninflamed rats (P < 0.05). Inhibitory effects of ACEA were significantly blocked by coadministration of the CB1 receptor antagonist SR141716A in both groups of rats. Peripheral injection of SR141716A alone did not alter mechanically evoked responses of spinal neurons in either group of rats. These data demonstrate that activation of peripheral CB1 receptors can inhibit innocuous and noxious somatosensory processing. Furthermore, following peripheral inflammation there is an enhanced inhibitory effect of a peripherally administered CB1 receptor agonist on both innocuous and noxious mechanically evoked responses of spinal neurons.

Animals↗

PubMed1995

Inhibition of intestinal tumor development in rat multi-organ carcinogenesis and aberrant crypt foci in rat colon carcinogenesis by 22-oxa-calcitriol, a synthetic analogue of 1 alpha, 25-dihydroxyvitamin D3.

The modifying effects of 22-oxa-calcitriol (OCT), a synthetic analog of 1 alpha,25-dihydroxyvitamin D3, were assessed in a multi-organ carcinogenesis model using male F344 rats initially treated with five kinds of carcinogens. In experiment 1 the rats were given OCT intraperitoneally at doses of 30 micrograms/kg (25 rats) or 3 micrograms/kg (25 rats), three times a week for 24 weeks after initial carcinogen exposure over 4 weeks and a 2 week non-treatment period. Twenty-two rats received the five carcinogens and were given the vehicle intraperitoneally as a control. A further group of 10 rats was given the 30 micrograms/kg dose of OCT without prior carcinogen application. At the end of the total observation period of 30 weeks the carcinoma incidence in the small intestine of rats given 30 micrograms/kg OCT after carcinogen treatment was 0%. This incidence was significantly smaller when compared with the control group. The incidence of large intestine carcinomas in the 30 micrograms/kg OCT group showed a tendency to decrease. The numbers of small and large intestinal carcinomas per rat were also significantly lower in the group given 30 micrograms/kg OCT than after 3 micrograms/kg OCT or carcinogens alone. Attention was, therefore, focused on colon carcinogenesis and in experiment 2 30 micrograms/kg OCT administered six times a week to rats for 8 weeks after the last injection of N,N'-dimethylhydrazine (DMH) exposure. OCT significantly reduced the formation of DMH-induced aberrant crypt foci, considered to be putative preneoplastic lesions. In experiment 3 30 micrograms/kg OCT was administered six times a week to rats for 4 weeks without prior carcinogen treatment. The proliferating cell nuclear antigen labeling index for the colonic epithelium of rats given 30 micrograms/kg OCT was decreased. Ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities in colonic epithelium, assayed as indicators of cell proliferation, were not significantly decreased as compared with control group values. Furthermore, vitamin D receptors in colonic epithelium were not significantly increased. Thus the present study indicates that OCT can exert inhibitory effects on tumor development in the small and large intestines, although the mechanism is unclear.

Acetyltransferases↗

PubMed1997

The association of yogurt starters with Lactobacillus casei DN 114.001 in fermented milk alters the composition and metabolism of intestinal microflora in germ-free rats and in human flora-associated rats.

The aim of this study was to compare the effects of milk and of various fermented milks on the composition and metabolic activities of the intestinal microflora. Groups of eight rats were fed for 6 wk a diet containing 30% nonfermented milk (M), yogurt (Y), milk fermented with Lactobacillus casei (LcFM) or milk fermented with the association of L. casei DN 114.001 and yogurt starters (LcYFM). In the first study, the survival of the lactic acid bacteria from the fermented milks was assessed by bacterial enumeration in feces of germ-free rats (GF rats) fed milk or fermented milks. The metabolic activities of the lactic acid bacteria were studied in these rats by the measurement of glycolytic activities and products of bacterial fermentation, i.e., acetate and lactate (isoforms L and D). In a second study, the effects of fermented milks on the composition and metabolism [gas, glycolytic activities, short-chain fatty acids (SCFA), alcohol and ammonia] of human flora were studied using human flora-associated rats (HF rats). In GF rats, the survival of L. casei in the feces did not differ between those fed the LcFM and LcYFM diets. L. bulgaricus was detected in the feces of the rats fed Y, whereas Streptoccus thermophilus was found in the feces of the LcYFM group. In HF rats, fecal concentration of Bifidobacteria was greater in the LcFM group than in the others. beta-Glucuronidase (EC 3.2.1.31) activity was lower in rats fed LcFM and Y than in those fed M and LcYFM, whereas beta-galactosidase (3.2.1.23), alpha-glucosidase (EC 3.2.1 20) and beta-glucosidase (EC 3.2.1.21) activities were higher in the LcYFM group compared with the others. Methane excretion was higher in rats fed Y than in other groups. Cecal SCFA concentrations did not differ in LcFM, Y and M groups, but total SCFA, acetate, propionate and butyrate were significantly greater in the LcYFM group. These results suggest that milk fermented with the combination of L. casei and yogurt starters leads to specific effects that are different from the simple addition of the effects found with yogurt and milk fermented with L. casei. These specific effects are potentially beneficial to human health.

Acetates↗

PubMed1994

Comparison of binding affinity of oxytocin antagonists to human and rat uterine oxytocin receptors and their correlation to the rat uterine oxytocic bioassay.

One of the primary methods used to screen the development of oxytocin antagonists (OTAs) is the rat oxytocic bioassay. The purpose of this study was to determine whether the rat oxytocic bioassay is a good predictor of binding affinity to human and rat uterine oxytocin receptors (OTr). The binding affinities of five OTAs to human and rat uterine OTr were determined and correlated with pA2 values derived from the rat uterine oxytocic bioassay. Human uterine myometrial tissue was obtained from patients at the time of cesarean section. Rat uterine tissue for the OTr assay was taken at Day 21 of pregnancy. OTr assays were accomplished by isolating uterine cell membranes and performing saturation analysis with cold OTAs and tritium-labeled oxytocin. The association constants (Ka; 10(+8)/M) were calculated by nonlinear curve-fitting techniques. The Ka for the five OTAs (Mpa1-OT, Antag I, L366948, Antag II, and Antag III), as estimated from the human OTr assay, were 0.55, 0.60, 2.27, 1.91, and 47.20, respectively. Ka estimates obtained through use of rat uterine membranes were 0.51, 1.16, 5.89, 2.03, and 24.40, respectively. Correlation of the log10 of the rat oxytocic bioassay results with those of the rat and human OTr assay was 0.94 and 0.98, respectively (p < 0.01). Antag III was approximately 55, 48, and 90 times more potent than Mpa1-OT as determined by the rat bioassay and rat and human uterine OTr assays, respectively. Mpa1-OT is an OTA that is currently undergoing clinical evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2000

Development of time-resolved immunofluorometric assays for rat follicle-stimulating hormone and luteinizing hormone and application on sera of cycling rats.

The aim of this study was to develop time-resolved immunofluorometric assays (TR-IFMA) for measuring rat (r)FSH and rLH. The advantages of these IFMAs are higher sensitivity due to lower background values, higher specificity as only intact molecules of FSH and LH can be measured, and a very long shelf life of the nonradioactive biotin antigens compared with radiolabeled iodine antigens. For rFSH, IFMAs are lacking, while for rLH, if present, the resources for antibodies are scarce or the mouse monoclonal antibodies (mMAbs) against LHalpha are inactive with FSH. Thus specific antibodies need to be obtained. With the final TR-IFMAs, rFSH and rLH levels were assessed during the estrous cycle and compared with those obtained with the more classical RIAs and fluoroimmunoassays (FIAs). Two IFMAs for rFSH were developed with mMAbs against the recombinant human (rec h)FSHbeta subunit (FSH56A) attached to the wall and two different rabbit polyclonal antibodies (PAbs) against the alpha subunit of rec hFSH (R93-2705) or recombinant rat (rec r)LH (R95-2715) conjugated with biotin as signal antibody. With both IFMAs, rFSH holo-molecules can be measured. Rat FSH standards could be assessed between 0.02 and 10 ng/ml with a detection limit of 0.05 and 0.24 ng/ml in buffer and serum, respectively. These detection limits in four IFMAs were 8- to 16-fold lower than those in RIAs and FIAs. This detection level allowed the measurement of FSH levels in serum of hypophysectomized (HYPEX) rats at 0.18 ng/ml. In serum of cycling rats, the FSH levels of the IFMA were 2-fold lower than those of the FIA, while in ovariectomized (OVX) rats the IFMA levels were comparable. A peak level of FSH was found during proestrus of Day 2 and gestation with both RIA and FIA, but with IFMAs at gestation only. An IFMA for rLH was set up with mMAb (hCG77A) reacting with rLHbeta as capture and rabbit PAb to rec rLHalpha (R95-2712) as signal antibody. Rat LH standard could be assessed between 0.001 and 10 ng/ml with a detection limit of 0.012 and 0.1 ng/ml in buffer and serum, respectively, which was 8-fold lower than that in RIA/FIA. In serum of HYPEX rats, LH was undetectable (< 0.04 ng/ml), whereas a high background level of 2.5 ng/ml was measured in the FIA. In serum of cycling rats, only a very low LH level of 0.14 ng/ml was measured, which strongly deviated from the level of 3.46 ng/ml with an FIA. The load of LH in serum of OVX rats was 2.91 ng/ml, which was 12-fold lower than that for the FIA. The peak level of LH was detected on proestrus Day 2 with RIA, FIA, and IFMA. In conclusion, two IFMAs for rFSH and one for rLH have been developed with high sensitivity and specificity for intact gonadotropins. The LH pattern during the estrous cycle was comparable between IFMA, RIA, and FIA, although the overall level in the IFMA was much lower, as were HYPEX levels. The FSH pattern differed only on proestrus Day 2 in the IFMA from that of RIA/FIA, showing a peak level with RIA/FIA and a basal level with the IFMA. This implies that in RIA/FIA measurements, proteins other than intact FSH and LH interfere with the analysis at proestrus Day 2 for FSH and in HYPEX, cycling, and OVX rats for LH.

Animals↗

PubMed1998

Different responses other than the formation of DNA-adducts between the livers of carcinogen-resistant rats (DRH) and carcinogen-sensitive rats (Donryu) to 3'-methyl-4-dimethylaminoazobenzene administration.

Carcinogen-resistant inbred DRH rats developed from the Donryu strain showed a remarkably low incidence of liver tumors when they were fed diets containing hepatocarcinogens such as 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). In this work, we examined various characteristics of male DRH and Donryu rats during 3'-Me-DAB administration for 8 weeks. 32P-Postlabeling analysis showed that essentially similar levels of DNA-adducts were generated by the metabolites of 3'-Me-DAB in the livers of these two strains of rats at several time points. However, both GADD45 (growth arrest and DNA damage-inducible) and O6-methylguanine methyltransferase (putatively DNA damage-inducible) mRNA levels were increased significantly in Donryu rat livers, but were increased to a lesser extent in DRH rats. [3H]Thymidine incorporation into hepatic DNA began to increase around 10 to 20 days after the start of 3'-Me-DAB administration in Donryu rats probably due to DNA repair, while no significant change occurred in DRH rats under the same conditions. Furthermore, inductions of heme oxygenase (due to degradation of heme-proteins) and hepatocyte growth factor (HGF; cell death and regeneration of hepatocytes) mRNAs were greater in Donryu rat livers than those of DRH, suggesting that the former were more sensitive to cytotoxic effects of 3'-Me-DAB than the latter. Another remarkable difference observed between these two strains was the significant induction of cytochrome P-450 2E1 mRNA in Donryu rat livers; this may contribute to the generation of reactive oxygen intermediates. Finally, increases of glutathione S-transferase (P-form) and gamma-glutamyltranspeptidase mRNAs as marker enzymes of preneoplastic changes of hepatocytes were clearly seen only in Donryu rat livers at 6 to 8 weeks after the start of 3'-Me-DAB administration. These results indicate that the different susceptibility to hepatocarcinogenesis between these two strains of rats may arise from events other than the DNA adduct formation.

Animals↗

PubMed2006

Susceptibility of newborn rats to 3-ethylphenol and 4-ethylphenol compared with that of young rats.

Newborn rat studies were conducted with oral administration of 3-ethylphenol (3EP) and 4-ethylphenol (4EP) on postnatal days (PND) 4-21 to allow comparison of no observed adverse effect level (NOAEL) and unequivocally toxic level (UETL) with those from 28-day studies of young rats starting at 5-6 weeks of age. In the newborn rat studies, slightly lowered body weight was observed after 3EP treatment, and deaths, hypoactivity, Straub tail, deep respiration and delayed righting reflex were clearly observed after 4EP treatment. In the young rat studies, salivation, staggering gait, changes in the liver including high values of liver weight and alanine aminotransferase or total cholesterol and the lesions in the forestomach were clearly observed after 3EP and 4EP treatments. NOAELs of 3EP and 4EP in the newborn rat studies appeared to be almost 3 times lower than those in the young rat studies. As a clear toxicity of 3EP was not observed in newborn rats, UETLs were not established for 3EP. Regarding 4EP, UETL of young rats was 4-5 times higher than that of newborn rats. In conclusion, newborn rats were 3-5 times more susceptible to 3EP and 4EP than young rats.

Administration, Oral↗

PubMed2003

High-impact exercise strengthens bone in osteopenic ovariectomized rats with the same outcome as Sham rats.

The effect of jump exercise on middle-aged osteopenic rats was investigated. Forty-two 9-mo-old female rats were either sham-operated (Sham) or ovariectomized (OVX). Three months after surgery, the rats were divided into the following groups: Sham sedentary, Sham exercised, OVX sedentary, and OVX exercised. Rats in the exercise groups jumped 10 times/day, 5 days/wk, for 8 wk, with a jumping height of 40 cm. Less than 1 min was required for the jump training. After the experiment, the right tibia and femur were dissected, and blood was obtained from each rat. OVX rats were observed to have increased body weights and decreased bone mass in their tibiae and femurs. Jump-exercised rats, on the other hand, had significantly increased tibial bone mass, strength, and cortical areas. The bone mass and strength of OVX exercised rats increased to approximately the same extent as Sham exercised rats, despite estrogen deficiency or osteopenia. Our data suggest that jump exercise has beneficial effects on lower limb bone mass, strength, bone mineral density, and morphometry in middle-aged osteopenic rats, as well as in Sham rats.

Animals↗

PubMed1983

Plasma prolactin concentrations in parental male and female rats: effects of exposure to rat young.

The effects of pup presentation on the PRL responses in parental male rats were measured and compared with those in parental virgin and lactating female rats. Blood samples were collected from rats through indwelling intraatrial cannulas after a suckling challenge, i.e. presentation of rat young. Lactating rats showed full parental behavior and characteristic large surges in plasma PRL levels within the first 5-10 min on each day that rat young were presented (days 4, 8, and 12 of lactation). When pups were not presented, PRL rises did not occur. In contrast to the pattern of PRL responses shown by lactating mothers, parental ovariectomized nulliparous female and parental intact male rats failed to show specific increases in PRL in response to pup presentation. Plasma PRL levels in these groups, as in nonparental female and male rats, occasionally rose in response to blood collection rather than to pup presentation alone. Treatment of nulliparous female as well as male rats with estradiol and progesterone Silastic implants for 21 days before the initiation of behavioral testing significantly reduced the latencies of both nulliparous females and males to respond to foster young from about 5 to 2 days. The PRL responses of these steroid-primed groups were quite different. The steroid-primed females exhibited a pattern of PRL responses to pups identical to that found in lactating rats. The steroid-primed parental males, in contrast, failed to show specific increases in plasma PRL levels in response to young. These data demonstrate a sex difference in the hormonal, but not behavioral, responses of male and female rats to young and are suggestive of possible sex differences in the hypothalamic and/or peripheral regulation of pup-induced PRL secretion.

Animals↗

PubMed1987

E-domain peptide of rat proinsulin-like growth factor-II: validation of a radioimmunoassay and measurement in culture medium and rat serum.

We recently discovered a peptide derived from the carboxyl-terminal portion of the E-domain of rat proinsulin-like growth factor II (pro-IGF-II) in medium conditioned by BRL-3A rat liver cells. This peptide begins at residue 117 in the pro-IGF-II sequence. To measure physiological concentrations of this peptide in serum, we established an RIA for a synthetic peptide [rat pro-IGF-II-(117-156); E-domain peptide] corresponding to the carboxyl-terminal 40-amino acids of rat pro-IGF-II. The 41-residue peptide [Tyr116]pro-IGF-II-(117-156) was also synthesized and iodinated for use as tracer. Using polyclonal antibodies, we established a standard curve that measured as little as 25 pg/tube. Tracer was not displaced by insulin, human (h) IGF-I, hIGF-II, pro-hIGF-I-(71-105), rat GH, mouse EGF, ACTH, bovine PTH, ovine FSH, TRH, or LHRH under our assay conditions. However, a synthetic analog of the E-domain peptide [Phe117]pro-IGF-II-(118-156) showed displacement similar to that of the synthetic E-domain peptide. Serial dilutions of either culture medium or rat serum exhibited displacement parallel to the standard curve. Measurement of E-domain peptide in serum-free medium conditioned by BRL-3A rat liver cells showed a time-related increase in E-peptide concentration over a 72-h period. Analysis of E-peptide immunoreactivity from conditioned medium after gel filtration chromatography in 1 M acetic acid revealed a single peak which had a mol wt (determined by Western blot) identical to that of the synthetic E-peptide standard. The concentration of immunoreactive E-domain peptide levels in serum of 5-day-old rat pups was 30-40 times higher than concentrations in the serum of adult rats. Gel filtration chromatography of adult rat serum in 1 M acetic acid revealed a single major peak of immunoreactivity eluting at a position similar to the elution position of the E-domain peptide from BRL-3A rat liver cell-conditioned medium. The RIA described here should prove useful for measurement of the somatic output of E-domain peptide under different physiological conditions.

Animals↗