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PubMed1975

Effect of urethan on the synthesis of nucleic acids in thymus, spleen, and bone marrow.

Urethan, in a single dose of 1 mg/g body weight, exerts a strong inhibitory effect on DNA synthesis in lymphoid organs and bone marrow of rat. The inhibition observed in spleen and thymus is longer lasting than that exerted on bone marrow or regenerating liver, demonstrating a marked sensitivity of lymphoid cells to the drug. This effect can explain the rapid reduction of weight and cell number in thymus and spleen under urethan treatment, in absence of any lymphocytolytic action. The different effect of urethan on the different subpopulations of lymphoid cells therefore appears to be due to their kinetics rather than to a specific sensitivity of some of them.

Animals↗
PubMed1979

[Effect of urethane and penthobarbital on the behaviour of the renin-angiotensin-system in rat (author's transl)].

The behaviour of the renin-angiotensin-system was investigated after urethane and penthobarbital anaesthesia in rats. The recent results support the early observation that urethane increases the plasma-renin-activity and the haematocrit. It was further shown that urethane in the customary anaesthetic dose causes hypoproteinaemia and a decrease in the pressor response to angiotensin and in renin substrate concentration. Based on these results, its use as an anaesthetic in experiments connected with the renin-angiotensin-system does not appear to be appropriate.

Anesthesia↗
PubMed1978

The effect of urethane and pentobarbital anaesthesia and hepatic portal vein catheterization on liver blood flow in the rat.

The effect of urethane and pentobarbital anaesthesia and hepatic portal vein catheterization on liver blood flow was investigated in the rat. Liver blood flow with pentobarbital anaesthesia was 40% greater than with urethane. Hepatic portal vein catheterization had no effect under pentobarbital anaesthesia whereas it produced an 18% fall in liver blood flow with urethane.

Animals↗
PubMed1986

Suitability of urethane anesthesia for physiopharmacological investigations in various systems. Part 2: Cardiovascular system.

Urethane produces a level of surgical anesthesia characterized by preservation of a number of cardiovascular reflexes. When the proper route of administration is used, and the use of unnecessarily high doses is avoided, urethane anesthesia appears to be suitable for a number of investigations at cardiovascular level. However in certain types of studies involving pharmacological stimulation of peripheral adrenoceptors urethane affects markedly the magnitude of the response under study.

Anesthesia↗
PubMed1986

Suitability of urethane anesthesia for physiopharmacological investigations. Part 3: Other systems and conclusions.

The suitability of urethane anesthesia for physiopharmacological experiments in various systems is briefly reviewed. Urethane anesthesia appears to be suitable for various types of studies on respiratory function and on reflex activation of motility of the urinary bladder and some sections of the intestinal tract. However, urethane produces a variety of potentially disturbing side-effects at endocrine and renal level.

Adrenal Glands↗
PubMed1994

Dentate gyrus and olfactory bulb responses to olfactory and noxious stimulation in urethane anaesthetized rats.

Recent research has shown that olfactory stimuli such as toluene vapor, but not visual, auditory, tactile or gustatory stimuli, elicit a burst of fast waves (15-30 Hz) in the hilus of the dentate gyrus in waking rats. In urethane-anaesthetized rats, toluene odors elicit similar fast waves. The present study shows that noxious stimulation (tail clamp) produces a blockade of spontaneous slow waves (1-12 Hz) in the hilus of the dentate gyrus but does not increase fast wave activity in urethane-anaesthetized rats. This slow wave blockade, which resembles neocortical activation, is independent of olfaction since it is not affected by tracheotomy. In contrast, tracheotomy abolishes the fast wave response to toluene presentation to the snout unless the toluene vapor is drawn into the nasal passages by suction at the rostral end of the severed trachea. Both the toluene odor-induced fast wave and the tail clamp-induced activation responses are abolished by scopolamine hydrobromide (5.0 mg/kg, i.p.) but not by scopolamine methyl bromide (5.0 mg/kg, i.p.) which does not cross the blood-brain barrier. However, evoked potentials elicited in the dentate hilus by single pulse stimulation of the olfactory bulb are not blocked by scopolamine in urethane-anaesthetized rats. The results suggest that several different types of electrical activity in the hippocampal formation are mediated by cholinergic inputs and that the dentate gyrus plays a role in olfaction.

Anesthesia↗
PubMed1980

Effect of urethan on polyamine and DNA synthesis in the regenerating rat liver.

When a single dose of urethan was injected into the peritoneal cavity of rats immediately after partial hepatectomy, DNA synthesis was delayed by 12 h. The induction of ornithine decarboxylase which was induced biphasically following partial hepatectomy was also reduced and delayed by 14-15 h by the administration of urethan. S-Adenosylmethionine decarboxylase activity in urethan-treated rat liver at 20 h and 29 h after operation was significantly lower than that of untreated animals. This enzyme activity was shown to increase thereafter, reaching a higher level than in untreated rats at 37-42 h. Hepatic spermidine content changed biphasically in a manner similar to DNA synthesis. These results suggest that the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase may correlate with DNA synthesis and that an increase of spermidine concentration is necessary to DNA synthesis.

Adenosylmethionine Decarboxylase↗
PubMed1990

Effects of urethane and ketamine on substance P- and excitatory amino acid-induced behavior in mice.

Urethane and ketamine were tested for their ability to alter the caudally directed binding and scratching response elicited by the intrathecal (i.t.) injection of excitatory amino acids (EAAs) or substance P (SP). EAAs, such as N-methyl-D-aspartate (NMDA), kainate acid and quisqualic acid, but not SP, were inhibited by subanesthetic doses of urethane. In contrast, SP was more sensitive than NMDA to the inhibitory effect of (+)-ketamine. (-)-Ketamine produced much less inhibition of the SP-induced behaviors than the (+)isomer. These results have important implications regarding the use of urethane and ketamine as anesthetics for studies in which these excitatory compounds are potential mediators.

2-Amino-5-phosphonovalerate↗
PubMed1987

Effects of H-2 complex and non-H-2 background on urethane-induced chromosomal aberrations in mice.

The incidence of in vivo urethane-induced chromosomal aberrations was examined in H-2 congenic strains of mice with B10 and A backgrounds. Chromosome analysis of bone-marrow cells could divide 7 lines of A.H-2 congenic strains into 2 groups: one with a higher frequency of chromosomal aberrations such as in A/Wy (haplotype H-2a), A/J (H-2a), A.AL (H-2al) and A.TL (H-2tl), and the other consisting of A.TH (H-2t2), A.CA (H-2f), A.BY (H-2b) and A.SW (H-2s). The same tendency was also observed in the spleen cells. Among B10.H-2 congenic mice, B10.A (H-2a), B10.BR (H-2k), B10.A(3R) (H-2i3), B10.A(5R) (H-2i5) and B10.S(9R) (H-2t4) exhibited significantly higher rates of induced chromosomal aberrations than those in B10 (H-2b), B10.S (H-2s), B10.A(2R) (H-2h2), B10.A(4R) (H-2h4) and B10.S(7R) (H-2t2). To determine the effect on non-H-2 genetic backgrounds on urethane-induced chromosomal aberrations, 4 pairs of strains which have the same H-2 haplotypes, such as in B10 vs. A.BY (H-2b), B10.A vs. A/Wy (H-2a), B10.S vs. A.SW (H-2s), and B10.S(7R) vs. A.TH (H-2t2), were compared. The strains with a B10 background exhibited significantly higher frequencies of deletions and lower frequencies of exchanges than the strains with an A background. These data suggested that at least two genes are involved in the regulation of urethane-induced chromosomal aberrations in mice, one of which is mapped between the S and D regions in the H-2 complex, and another not belonging to H-2.

Animals↗
PubMed1994

LTP in hippocampal CA1 of urethane-narcotized rats requires stronger tetanization parameters.

Rats with chronically implanted electrodes in the hippocampal CA1 region were tested in their capacity to express and maintain long-term potentiation (LTP) of the population spike (PS) or of the field excitatory postsynaptic potential (fEPSP). Two different states were compared: a) freely moving animals; b) urethane-anesthetized animals (1 g/kg, IP). We found that a short, high-frequency tetanus (six bursts of 15 pulses; 200 Hz; double-pulse width; interburst interval 10 s) increased PS amplitudes and fEPSP slopes up to 300% in response to test stimuli in double-pulse width; interburst interval 10 s) increased PS amplitudes and fEPSP slopes up to 300% in response to test stimuli in the awake rat. The PS amplitude slowly decreased in time, returning to baseline levels 4 h post-tetanically, whereas the fEPSP slope remained at higher values for 24 h. Urethane injection reduced the fEPSP slope and abolished the PS to normal test pulses. We thus increased the strength of the test stimuli until we again recorded magnitudes of PSs and fEPSPs comparable to those in the awake animal. In conjunction with these stronger stimuli, tetanus-induced LTP was elicited that for the PS was increased in magnitude and prolonged in duration compared to the untreated control group. Although, stronger tetanic stimuli were applied to the narcotized fEPSP group too, no difference was found compared to controls. These results suggest that urethane narcosis influences the sensitivity of CA1 neurons to express LTP. Stronger stimulation was required to induce and maintain a long-lasting potentiation of the fEPSP slope and PS amplitude.

Animals↗
PubMed1989

In vivo cystometrogram studies in urethane-anesthetized and conscious guinea pigs.

Urinary bladder cystometry using urethral catheters is described in vivo in a urethane-anesthetized guinea pig preparation and compared to an awake-animal preparation in which surgically implanted catheters were used. Anticholinergic drugs dose-dependently inhibited the peak intravesical pressure (PvesP) to a maximum of approximately 80% but had no effect on other cystometrogram (CMG) parameters (threshold pressure, bladder capacity). Stereoselectivity was evident; dexetimide but not levetimide potently depressed PvesP. Oxybutynin was equipotent (ID50 approximately 0.15 mg/kg) in both preparations and showed a similar duration of action (t1/2 = 48-53 min). The data suggests that CMG parameters and the effects of oxybutynin were not affected by urethane anesthesia, making the in vivo urethane-anesthetized guinea pig preparation a valuable tool to evaluate both the filling and voiding phases of cystometry.

Anesthesia↗
PubMed1981

Multicellular in vivo sister-chromatid exchanges induced by urethane.

Following urethane inhalation exposure, clear dose--response relationships were apparent in all cell types examined in hepatectomized and intact mice. At concentrations of 0.1 mg/l and higher, induced SCE frequencies were linearly related to log urethane concentrations. No significant differences in SCE response between like cell types of hepatectomized and intact mice were apparent. In hepatectomized mice, there was no significant difference in the SCE response of regenerating liver and alveolar macrophage cells. However, bone-marrow response was significantly lower (p = 0.01). Likewise, in intact mice bone marrow response was significantly lower than in alveolar macrophages (p = 0.01). Inhalation and intravenous infusions of the same total dose of urethane (193 mg/kg) administered over a 4-h period produced comparable SCE responses in all cell types. However, a single intraperitoneal injection of 193 mg/kg just prior to BrdU infusion produced significantly higher SCE frequencies in bone marrow (alpha = 0.01), and alveolar macrophages (alpha = 0.05) of intact mice than did the equivalent inhalation dose. Intraperitoneal injections produced similar results in 2-month-old mice as in 4-month-old mice. However, regardless of the route of administration SCE frequencies in regenerating liver and/or alveolar macrophages were significantly higher than in bone marrow.

Aerosols↗
PubMed1987

Tests for urethane induction of germ-cell mutations and germ-cell killing in the mouse.

Urethane, a chemical that has given varied results in mutagenesis assays, was tested in the mouse specific-locus test, and its effect on germ-cell survival was explored. Altogether 32,828 offspring were observed from successive weekly matings of males exposed to the maximum tolerated i.p. dose of 1750 mg urethane/kg. The combined data rule out (at the 5% significance level) an induced mutation rate greater than 1.7 times the historical control rate. For spermatogonial stem cells alone, the multiple ruled out is 3.2, and for poststem-cell stages, 3.5. Litter sizes from successive conceptions made in any of the first 7 weeks give no indication of induced dominant lethality, confirming results of past dominant-lethal assays. That urethane (or an active metabolite) reaches germ cells is indicated by SCE induction in spermatogonia demonstrated by other investigators. Cytotoxic effects in spermatogonia are suggested by our finding of a slight reduction in numbers of certain types of spermatogonia in seminiferous tubule cross-sections and of a borderline decrease in the number of litters conceived during the 8th and 9th posttreatment weeks. The negative results for induction of gene mutations as well as clastogenic damage are at variance with Nomura's reports of dominant effects (F1 cancers and malformations) produced by urethane.

Animals↗
PubMed1990

Effect of urethane anesthesia on the micturition reflex in capsaicin-treated rats.

Cystometry was performed on rats with a chronically implanted intravesical catheter (2 days before cystometry) before and after induction of urethane-anesthesia. Four groups of animals were investigated: group A, vehicle-treated; group B, capsaicin-treated as adults (50 mg/kg s.c.) 4 days before cystometry; group C, capsaicin-treated as adults (125 mg/kg s.c.) 4 days before cystometry; and group D, capsaicin-treated as newborns (50 mg/kg) 2 months before. Rats of group D had a markedly enlarged bladder. Before induction of urethane anesthesia, the bladder capacity of rats of groups A, B and C was not significantly different from each other, while that of rats of group D was larger than controls. After induction of anesthesia bladder capacity in groups B and C was significantly increased as compared to group A and micturition was abolished in group D (overflow incontinence). Amplitude of micturition contraction was significantly reduced in all groups after induction of anesthesia but was unaffected by capsaicin pretreatment. It is concluded that the facilitatory action of capsaicin-sensitive nerves on micturition threshold is more evident in anesthetized than awake rats and that capsaicin-resistant bladder afferents are more sensitive to the depressant action of urethane than the capsaicin-sensitive ones.

Anesthesia↗
PubMed1995

Mutations of the Ki-ras protooncogene in 3-methylcholanthrene and urethan-induced and butylated hydroxytoluene-promoted lung tumors of strain A/J and SWR mice.

Mutations of the Ki-ras protooncogene in 190 lung tumors initiated in male A/J and SWR mice by 3-methylcholanthrene(MCA) or urethan and promoted by butylated hydroxytoluene (BHT), were evaluated by utilizing polymerase chain reaction (PCR) and sequencing analysis. The most common mutation pattern was a GC to CG transversion at the first base of codon 12/13. The predominant mutation pattern at codon 61 was an AT to TA transversion and the next frequent one an AT to GC transition. Mutations of Ki-ras codon 12/13 were found in 44% (A/J) and 13% (SWR) of MCA-induced and in 94% (A/J) and 43% (SWR) of MCA plus BHT-induced lung tumors. Mutations of the Ki-ras codon 61 were found in 31% (A/J) and 13% (SWR) of urethan-induced and 69% (A/J) and 44% (SWR) of urethan plus BHT-induced lung tumors. These data suggest that in strain A/J mice the 2 carcinogens produce Ki-ras mutations and that BHT promotes the activations of Ki-ras protooncogenes in lung tumors.

Animals↗
PubMed1989

Urethane as a sole general anaesthetic in cats used for electroretinogram studies.

Cats are very sensitive to induction of anaesthesia by urethane. To anaesthetize cats with urethane, 1.0-1.3 g/kg, of freshly prepared urethane is administered intravenously at a rate of 1.92 g/h, while anaesthesia is maintained with 0.5% halothane in a 66%/33% nitrous oxide/carbogen gas mixture. Cats can then be maintained for up to 3 days by intravenous infusion at a rate of 4 ml/h of a 100 ml solution containing 50 IU heparin, 2.4 mg atropine, 4.7 g anhydrous D-glucose, and 240 mg urethane/kg. Using this anaesthetic, excellent electroretinograms can be recorded with no interfering eye movements.

Anesthesia↗
PubMed1988

Metabolic changes induced by urethane-anesthesia in rats.

1. Fasting hyperglycemia was observed in urethane-anesthetized rats. No significant changes had been observed in fed animals. The effect is dose-dependent, being ineffective doses lesser than 1.4 g/kg of body weight. 2. Urethane originates a rise in glycemia during the first 10 min of anesthesia followed by control values at 30 min, and a latter hyperglycemic phase for more than 60 min that remain at 2 hr. 3. The negative correlationship between plasma glucose, lactate and amino acid levels suggest that gluconeogenesis may be the main responsibility of the observed hyperglycemia during the first phase, but it is possible that during the second phase a decrease in the consumption of glucose may take place as a consequence of the competitive effects of ketone bodies increased during the first 30 min of anesthesia. 4. We postulate that the mechanism of the hyperglycemic response to urethane is a sympathetic response with release of catecholamines both in the liver and in the adrenal gland which enhances gluconeogenesis and lipolysis.

Amino Acids↗
PubMed1992

Differential effects of hypothermia upon blood acid-base state and blood gases in sodium pentobarbital and urethane anaesthetised rats.

1. The effects of two anaesthetics, sodium pentobarbital and urethane, and the effects of anaesthesia-associated hypothermia on acid-base status and blood gases were studied in rats without assisted ventilation. 2. Manipulation of conscious rats produces a progressive increase in arterial lactate associated with slight hyperventilation. 3. Sodium pentobarbital anaesthesia produces mild respiratory acidosis accompanied by increase in lactate arterial values. Urethane anaesthesia leads to partially compensated metabolic acidosis. 4. Hypothermia reduces metabolic acidosis and hypercapnia induced by sodium pentobarbital anaesthesia. No difference between hypothermic and normothermic values was observed in urethane anaesthesia.

Acid-Base Equilibrium↗