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Biomedical subjects

G L Sprague

Publications and source records attributed to G L Sprague.

16 recordsLinked to original sources
PubMed1988

Hepatic changes in rats following subchronic administration of FYROL 6, an organophosphorus ester flame retardant.

This study conducted to evaluate the subchronic toxicity of FYROL 6 [diethyl N,N-bis-(2-hydroxyethyl)aminomethylphosphonate] in rats demonstrated an hepatic effect not commonly reported for related compounds. Sprague-Dawley rats of both sexes were gavaged daily with 0, 10, 100, or 500 mg/kg FYROL 6 in corn oil for 13 wk. No treatment-related mortality and few signs of toxicity were noted during the study. Fyrol 6 did not inhibit plasma, erythrocyte, or brain cholinesterase activities. Treatment-related necropsy and microscopic alterations were restricted to the liver. Increased liver weights, hepatocellular hypertrophy, and eosinophilia of centrilobular hepatocytes were evident in 100-mg/kg females and in both sexes at 500 mg/kg. Morphometric analysis revealed a 40% increase in cross-sectional area of individual hepatocytes in 500-mg/kg males, compared to controls. There was no morphologic evidence of hepatic necrosis or clinical evidence of liver dysfunction. This study demonstrated low toxicity for FYROL 6 and treatment-related changes restricted to the liver suggestive of an adaptive response to FYROL 6.

Animals↗
PubMed1987

Anticholinesterase effect and toxicity of bis(trichloromethyl) sulfone (N-1386 Biocide) in rats.

The oral LD50 for bis(trichloromethyl) sulfone (N-1386 Biocide) in male rats was 691 mg/kg. Deaths occurred 1-5 days after treatment and signs of toxicity suggestive of an anticholinesterase effect were noted. However, neither plasma cholinesterase nor brain acetylcholinesterase was inhibited 2, 4 or 24 hours after a single, oral dose of 500 mg/kg. Atropine (300 mg/kg, s.c.) or scopolamine (670 mg/kg, s.c.) pretreatments did not protect against the acute lethality of bis(trichloromethyl) sulfone although signs of toxicity were alleviated by both pretreatments. Bis(trichloromethyl) sulfone produced in vitro inhibition of rat plasma cholinesterase and brain acetylcholinesterase. The inhibition was competitive in brain. IC50's for these 2 enzymes were 8 microM in plasma and 25 microM in brain. In summary, bis(trichloromethyl) sulfone produced in vitro cholinesterase inhibition not demonstrated in vivo. Doses of anticholinergic compounds that ameliorated many toxic signs did not protect against lethality produced by bis(trichloromethyl) sulfone.

Animals↗
PubMed1987

Toxicity and aluminium concentration in bone following dietary administration of two sodium aluminium phosphate formulations in rats.

The effects of dietary administration of the basic sodium aluminium phosphates, KASAL and KASAL II, were examined in male rats. Aluminium levels in bone were determined in order to estimate the possible aluminium deposition by these compounds. Groups of 25 male Sprague-Dawley rats were fed control diet or diets containing 30,000 ppm KASAL, 7000 or 30,000 ppm KASAL II, or 14,470 ppm aluminium hydroxide for 28 days. The mean daily aluminium doses were calculated to be 5, 141, 67, 288 or 302 mg/kg body weight/day, respectively. Neither form of KASAL induced detectable toxicity. No adverse treatment-related clinical signs were observed. Body weights and food consumptions were similar in treated and control groups. No toxicologically significant changes were observed in haematology, clinical chemistry parameters or organ weights. No treatment-related changes were observed at autopsy or in histopathological examination of collected tissues. Femurs collected at autopsy under conditions free of aluminium contamination showed no significant deposition of aluminium after dietary administration of KASAL, KASAL II or aluminium hydroxide. All aluminium values in bone were less than 1 ppm and most values were not quantifiable. Thus, dietary administration of up to 30,000 ppm of either of the basic sodium aluminium phosphate formulations caused neither toxicity nor significant deposition of aluminium in femur.

Aluminum↗
PubMed1985

Estimation of the delayed neurotoxic potential and potency for a series of triaryl phosphates using an in vitro test with metabolic activation.

The delayed neurotoxic potential of 0,0-diphenyl-o-tolyl phosphate (MOCP), tri-o-tolyl phosphate (TOCP), 0,0-diphenyl-m-tolyl phosphate (MMCP), tri-m-tolyl phosphate (TMCP), 0,0-diphenyl-p-tolyl phosphate (MPCP) and tri-p-tolyl phosphate (TPCP) was determined using an in vitro neurotoxic esterase test with metabolic activation. None of the 6 compounds inhibited hen brain neurotoxic esterase activity in vitro when tested in the absence of metabolic activation using concentrations as high as 100 microM. Both MOCP and TOCP markedly inhibited activity in vitro after metabolism with rat liver microsomes. MOCP was twice as potent as TOCP and IC50 values were 6.2 and 12 microM, respectively. Adult hens were treated with 10 mg/kg MOCP, 10 mg/kg TOCP, 1000 mg/kp MMCP, 1000 mg/kg TMCP, and 1000 mg/kg TPCP. There was no inhibition of brain neurotoxic esterase 24 hours after MMCP, TMCP or TPCP. Inhibition by MOCP and TOCP was 86.8% and 40.7% respectively. The in vitro neurotoxicity test showed that MOCP and TOCP, 2 known neurotoxicants, had delayed neurotoxic potential and metabolism was required. The test also showed that the potency of MOCP was twice that of TOCP. This was confirmed in hens dosed with the 2 compounds since MOCP produced twice the inhibition of brain neurotoxic esterase as that produced by an equal dose of TOCP.

Animals↗
PubMed1984

Assessment of the delayed neurotoxic potential of isopropyl triphenylphosphate using a nontraditional testing strategy.

The potential of isopropyl triphenyl phosphate (ITP) to produce delayed neurotoxicity in hens was examined using several techniques. ITP contained O,O,O-triphenyl phosphate (24%), O-o-isopropylphenyl O,O-diphenyl phosphate (25%), O,O-diisopropyl-phenyl O-phenyl phosphate (20%), O-o, p-diisopropylphenyl O,O-diphenyl phosphate (18%) and O-p-isopropylphenyl O,O-diphenyl phosphate (6%). Hens treated twice, 3 wk apart, with doses of ITP as high as 11.7 g/kg showed no clinical signs of delayed neurotoxicity and only mild signs of general toxicity. Furthermore, none showed even subtle neurohistologic changes suggestive of delayed neurotoxicity. ITP produced dose-dependent inhibition of hen plasma cholinesterase and brain neurotoxic esterase (NTE). The study was continued because NTE inhibition has been shown to be a reliable predictor of organophosphates that produce delayed neurotoxicity. ITP was administered prior to tri-o-tolyl phosphate (TOCP) challenge in order to determine if it altered development of TOCP delayed neurotoxicity. ITP neither enhanced nor reduced the onset or severity of neurotoxicity produced by TOCP. The time-course for brain and spinal cord NTE inhibition by ITP and TOCP were compared and found to be different. The maximum brain NTE inhibition produced by ITP (doses up to 11.7 g/kg) was never complete (always less than 90%), and spinal cord NTE inhibition was significantly less than that produced in the brain. In contrast, brain and spinal cord inhibition produced by 500 mg TOCP/kg were equal and greater than 90%. This testing regimen showed that ITP produced an effect on NTE at the biochemical level without producing clinical or neurohistologic abnormalities in treated hens. Furthermore, this biochemical effect was qualitatively different than that produced by the delayed neurotoxicant TOCP.

Animals↗
PubMed1979

Improved method for morphine extraction from biological samples.

Methadone morphine, or naloxone extraction from brain homogenates, plasma, and urine is described. An aqueous sample was loaded on a surgical gauze support, which was washed with extracting solvents. Aqueous samples remained on the support, and nonpolar drugs partitioned into the lipophilic extracting solvent. The procedure recovered 80-100% of nanogram levels of methadone, morphine, or naloxone from biological samples. In addition, an approximate 10-fold timesaving capacity was demonstrated compared to standard liquid-liquid extraction techniques.

Animals↗
PubMed1978

Effects of two cannabinoids upon abstinence signs in ethanol-dependent mice.

The effects of delta9-tetrahydrocannabinol (THC) and nabilone, a synthetic cannabinoid, upon handling-induced convulsions and responsiveness to electric foot shock were examined during abstinence in ethanol-dependent mice. The severity of handling-induced convulsions was apparently increased by THC (10-40 mg/kg) and nabilone (2.5-10 mg/kg) but both drugs elicited similar convulsions in normal mice never exposed to ethanol. Enhanced responsiveness to electric foot shock, evident during abstinence, was suppressed by THC (10-40 MG/KG). The effects of ethanol upon the two abstinence signs were determined for comparative purposes. Ethanol (0.5-4 g/kg) reduced the severity of handling-induced convulsions and suppressed the increased responsiveness to electric foot shock. These results indicate that THC and nabilone have similar actions upon two abstinence signs in ethanol-dependent mice, and although one sign (responsiveness to electric foot shock) was clearly alleviated, another (handling-induced convulsions) was not.

Alcohol Drinking↗
PubMed1978

Alteration of brain chromatin and nuclear synthetic activity in morphine-tolerant rats.

3H-UTP incorporation by endogenous RNA-polymerase of intact, isolated rat brain nuclei was enhanced by chronic morphine treatment. Analgesic tolerance using the hot-plate assay was also evident. Fractionation proflies for brain chromatin on hydroxylapatite from morphine and vehicle-treated rats was different. These results suggest that morphine-tolerance in the rat may be accompanied by enhanced nuclear synthesis of a new species of RNA.

Analgesia↗
PubMed1978

Enhancement of morphine analgesia and brain levels by methamphetamine in mice.

Methamphetamine and morphine were approximately equipotent in producing analgesia in mice using the tail-flick assay. The ED50 for morphine analgesia was significantly reduced when 3.2 mg/kg of methamphetamine was given 5 or 60 min before morphine. Methamphetamine pretreatment increased the peak effect but did not alter the duration of morphine analgesia. Enhancement of morphine analgesia was apparent when methamphetamine was given up to 60 min before morphine and it did not coincide with analgesia produced by methamphetamine alone. Brain levels of morphine were found to be significantly higher in methamphetamine- compared to saline-pretreated mice, at times when enhanced analgesia was observed. Further studies showed that morphine brain levels were increased by methamphetamine pretreatment in an apparent dose-dependent manner. The analgesia observed at several morphine brain levels was compared in order to determine whether enhanced analgesia resulted from increased morphine brain levels. Methamphetamine administration 5 or 60 min before morphine shifted the log morphine brain level-response curves for morphine analgesia to the left and the morphine brain level at a given percent analgesia was significantly lower in methamphetamine- than in saline-pretreated mice. In addition, methamphetamine pretreatment enhanced methadone analgesia but had no effect on methadone brain levels.

Analgesia↗
PubMed1976

Ethanol and delta-9-tetrahydrocannabinol: mechanism for cross-tolerance in mice.

The pharmacological interaction between equipotent doses of ethanol (1.35 g/kg) and delta-9-tetrahydrocannabinol (THC, 17 mg/kg) was evaluated in mice using rotarod performance as a measure of drug action. Tolerance ot the effects of ethanol and THC as well as a symmetrical cross-tolerance between these two drugs was demonstrated. Ethanol elimination was not altered by previous treatment with either ethnaol or THC as determined by measuring blood ethanol concentrations with an enzymatic assay. THC metabolite ratios in blood, brain and liver tissues determined after a dose of 3H-THC demonstrated that THC treatment had no effect upon THC metabolism or disposition. Ethanol treatment altered the distribution of THC and also altered hepatic THC metabolism as evidence by the occurrence of increased proportions of polar THC metabolites. No treatment regimens produced lower whole brain levels of subsequent ethanol or THC suggesting that tolerance to ethanol or THC and cross-tolerance between these two drugs does not develop due to lower brain concentrations. A vehicle effect was shown when treatment with a mixture of propylene glycol and Tween-80 altered the metabolic and behavioral effects of subsequently administered THC.

Animals↗
PubMed1976

Control of ethanol withdrawal symptoms in mice by phenytoin.

Mice were made physically dependent upon ethanol using either of two methods which involved ethanol vapor inhalation. Following the cessation of exposure to ethanol, the severity of handling-induced convulsions and changes in the response to an electric foot shock (startle reflex) were recorded. Animals given isotonic saline or propylene glycol:ethanol vehicle during withdrawal exhibited handling-induced convulsions, and ethanol (2.0-4.0 g/kg) or phenytoin (5-20 mg/kg) administration during withdrawal resulted in a reduction in the severity of these convulsions. A reduced startle reflex threshold was also evident during withdrawal in mice given isotonic saline or propylene glycol:ethanol vehicle. Ethanol (0.5-4.0 g/kg) or phenytoin (10-20 mg/kg) administration during withdrawal resulted in a significant elevation of the startle reflex threshold compared to control animals. The results are discussed as they relate to others obtained in experimental and clinical studies.

Animals↗