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Biomedical subjects

H Vainio

Publications and source records attributed to H Vainio.

At least 325 records · Page 18Linked to original sources
PubMed1978

Interaction of styrene and acetone with drug biotransformation enzymes in rat liver.

In the presence of hepatic microsomes, styrene produced a type I difference spectrum, which demonstrates that styrene binds to the catalytic site of ferricytochrome P-450. A comparison of the binding parameters for the interaction of styrene with noninduced, phenobarbital-induced, and 3-methylcholanthrene-induced microsomes indicated that styrene is predominantly bound by cytochrome P-450 and not by cytochrome P-448. Inhalation exposure to a mixture of acetone (1,000 ppm, 6 h/d) and styrene (300 ppm, 6 h/d) for 5 d caused a distinct decrease in hepatic free nonprotein sulfhydryl groups. This decrease could be observed both with and without phenobarbital treatment. Acetone inhalation alone also enhanced ethoxycoumarin O-deethylase activity in rats without pretreatments. Acetone inhalation also increased the cytochrome P-450 content of liver microsomes, but it had no effect on NADPH cytochrome c reductase or epoxide hydratase activity. Combined exposure to styrene and acetone enhanced NADPH cytochrome c reductase activity in nonphenobarbital-treated rats, but no effect was seen in the phenobarbital-treated animals. Phenobarbital treatment of animals can greatly modify the biotransformation and toxicity of styrene, phenobarbital inducible P-450 hemoprotein playing a predominant role in its metabolism. Simultaneous inhalation exposure to acetone also interacts with the metabolism of styrene.

Acetone↗
PubMed1978

Effects of thermal degradation products of polystyrene on drug biotransformation and tissue glutathione in rat and mouse.

Rats and mice were exposed to the fumes of oxidative thermal degradation of polystyrene (350 degrees C). A decrease in the reduced glutathione (GSH) in both liver and lung was detected immediately after both the acute (mice, 3 h) and subacute (rats, 3 weeks) exposures were stopped. Later on an elevation in the amount of GSH due to the increased synthesis (rebound effect) could be seen. Cytochrome P-450 content in mouse liver was initially decreased after acute exposure, but the prolonged treatment doubled the amount of the P-450 hemoprotein in liver microsomes. After acute exposure 7-ethoxycoumarin 9-deethylase activity in mouse liver was doubled in 24 h. When the exposures were continued, this enhancement in ethoxycoumarin O-deethylase activity gradually disappeared. O-deethylase activity was also enhanced in rat liver and lung after subacute exposure. The exposures given had no effect on diphenyloxazole hydroxylase, and the effects on the conjugating enzymes (epoxide hydratase, UDPglucuronosyltransferase, glutathione S-transferase)) were insignificant in rat liver.

Animals↗
PubMed1977

Trichloroethylene and 1,1,1-trichloroethane: effects on brain and liver after five days intermittent inhalation.

The inhalation exposure of adult male rats to 7.9 mumol/l (200 ppm) of trichloroethylene for 4 days 6 h each day led to an accumulation of the solvent in the perirenal fat 17 h after the last exposure. Exposures to 20 mumol/l (500 ppm) of 1,1,1-trichloroethane caused similar accumulation. The latter rats presented no changes in their behaviour in an open-field test whereas the motor behaviour of the animals exposed to trichloroethylene was more active in comparison to controls 1 h after the exposure on the 4th day. Trace effects of trichloroethylene on emotional behaviour of the same rats could be seen 17 h after the last exposure. Further exposures on the 5th day increased brain, liver, lung and blood contents of trichlorethylene and 1,1,1-trichloroethane. A slight decrease in brain RNA content was found in the 1,1,1-trichloroethane exposed rats while RNA decreased significantly after the fifth day of trichloroethylene inhalation. The exposure to 1,1,1-trichloroethane on the 5th day depressed also the microsomal cytochrome P-450 content in liver of rats whereas trichloroethylene increased the hemochrome content slightly at the same time.

Animals↗
PubMed1977

CS2 binding to rat spinal neurofilaments.

The binding of CS2 sulphur to rat spinal cord neurofilaments was studied 3 and 6 h after the intraperitoneal injection of 1.3 mmol of CS2 in control and phenobarbitone pretreated rats. The binding of CS2 carbon was studied similarly 3 h after the injection. The binding of CS2 sulphur was 31% higher in the control neurofilaments than that in the phenobarbitone pretreated group. Half of the neurofilament associated CS2 sulphur was bound to protein in both groups as studied by electrophoresis. Approximately 30% of the neurofilament associated CS2 sulphur was detected 6 h after the injection of that at 3 h in both groups. All of the neurofilament associated CS2 carbon was bound to protein in control group 3 h after the injection. The binding of CS2 carbon was 4.7 times less than that of sulphur at the same time. The present data may indicate that the high binding of CS2 to the neurofilament protein contributes to the increase in neurofilaments in chronic CS2 intoxication.

Animals↗
PubMed1977

Organ distribution and nervous system binding of styrene and styrene oxide.

Ten adult male rats were injected intraperitoneally with 460 mumol of styrene oxide with radioactive label. Fifteen similar rats were injected similarly with 577 mumol of styrene. The distribution of styrene in central nervous system, blood, liver, lungs, kidneys and duodenum was studied 3, 6 and 24 h after the injection while the same studies were done with styrene oxide 3 and 6 h after the injection. The liver, brain, kidney and duodenal contents of styrene and styrene oxide were higher than that in blood, lungs and spinal cord while the macromolecule-associated styrene oxide in the central nervous system was small. The removal of injected compounds was slow between 3 and 6 h after the injection in the organ systems although lipid-soluble compounds tended to diminish in brain more rapidly than the total radioactivity.

Animals↗
PubMed1977

The binding of CS2 in central nervous system of control and phenobarbitone-pretreated rats.

The binding of 35S- and 14C-labelled CS2 in rat central nervous system (CNS) was studied in control and phenobarbitone-pretreated rats in vivo and in vitro. Animals received CS2 through intraperitoneal injection in olive oil. Samples were taken for analysis 3 and 6 h after the injection. Sulphur atoms were bound to rat brain more highly than carbon atoms in control and phenobarbitone-pretreated rats in vivo. The phenobarbitone pretreatment increased the cerebral binding of sulphur and decreased that of carbon. Main part of the bound sulphur and carbon was detected in the trichloroacetic acid (TCA) precipitable fraction in both test groups. Pretreatment with phenobarbitone or with polychlorinated hydrocarbon (PCB) mixture did not increase significantly the binding of CS2 sulphur in brain microsomes in vitro. The present findings suggest that a considerable amount of injected CS2 is retained in the nervous system and that phenobarbitone pretreatment of test subjects may also alter brain metabolism of CS2.

Animals↗
PubMed1977

Toxicity of styrene and styrene oxide on chick embryos.

Styrene and styrene oxide were injected into the air space of fertilized chicken eggs at different times during an incubation period of 14 days. The toxicity of styrene and styrene oxide when injected on the fourth day of incubation revealed an LD50 of 40 mumol/egg and 1.5 mumol/egg, respectively. Malformations were found in 0-20% of the embryos, but never in the controls. The results obtained point to a need for further experimental, and possibly epidemiologic, studies on the consequences of styrene exposure.

Animals↗
PubMed1977

Long-term effects of single and combined doses of DDT and PCB on drug-metabolizing enzymes in rat liver.

Two common environmental pollutants, DDT and a polychlorinated biphenyl (PCB) mixture (Clophen A-50), were administered ip to rats in discrete single doses (160 and 100 mg/kg, respectively) and in combination. All the enzyme activities studied were enhanced by DDT and PCB. the overall drug hydroxylation reactions, and their components, achieved maximal induction in 1 wk. The cytochrome P-450 content of microsomes was increased nearly fourfold and NADPH-cytochrome c reductase activity was enhanced twofold by both compounds. p-Nitroanisole O-demethylase was increased sevenfold by PCB and fourfold by DDT, aryl hydrocarbon hydroxylase threefold by PCB and 1.7-fold by DDT. After 2 wk the activities began to decline. Distinct increases in enzyme activities were still detectable 1 month after a single dose. Epoxide hydratase and UDPglucuronosyltransferase activities were also enhanced in 1 wk (epoxide hydratase 2.5-fold by both compounds, UDPglucuronosyltransferase tenfold by PCB in trypsin-activated microsomes but only threefold by DDT). The disappearance of induction in epoxide hydratase was slower than in the monooxygenases, and UDPglucuronosyltransferase still showed a trend toward increased activity 4 wk after the administration. The DDT-enhanced UDPglucuronosyltransferase activity slightly returned toward the control level. Glutathione S-transferase differed from the microsomal enzymes in that it was already elevated 1 day after the administration of both DDT and PCB. Its activity was only doubled, but the increased activity remained at almost the same level through the whole 1 month period.

Animals↗
PubMed1977

Biochemical and behavioural effects of inhalation exposure to tetrachlorethylene and dichlormethane.

The exposure of adult male rats to 200 ppm of tetrachlorethylene t hours daily for 4 days resulted in a marked sequestration of solvent in perirenal fat 17 hours after the last exposure period. Similar exposure of similar rats to 500 ppm of dichlormethane led to a lesser accumulation of the solvent in fat as studied at the same time. Further exposures on the fifth day increased promptly the solvent contents of various organs. The exposure to tetrachlorethylene caused a diminished brain RNA content on the fifth day with simultaneous increase in the activity of non-specific cholinesterase. Similar changes in the RNA content were not seen in experiments with dichlormethane while the activity of acid proteinase increased above the control level in brain. Observations on the performance of the same animals in an open-field situation revealed that ambulation was affected in experiments with tetrachlorethylene immediately after exposure while preening pattern was changed after exposure to dichlormethane. Analysis on liver microsomal cytochrome P-450 content displayed slight increases in the hemochrome content in both experiments. The present data indicated that a rather modest exposure to both solvents could cause significant solvent accumulation in the fat and brain with marked effects on rat behaviour and protein metabolism in brain while changes in liver cytochrome P-450 content might not reflect the magnitude of these changes.

Adipose Tissue↗
PubMed1977

The in vivo toxicity of CS2 to liver microsomes: binding of labelled CS2 and changes of the microsomal enzyme activities.

The binding of 35S and 14C labelled CS2 to liver microsomes was studied in control and phenobarbitone pretreated rats 3 and 6 hrs after an intraperitoneal injection. The level of hepatic cytochrome P-450, the activities of epoxide hydratase and UDP-glucuronosyltransferase were analyzed in the same animals. The binding of the sulphur label was considerably higher than that of carbon 3 hrs after the injection, the difference being less evident at 6 hrs.T he measurable P-450 declined after the CS2 injection. It was approximately 40% in the phenobarbitone pretreated rats and 60% in control rats of the values of animals which were not treated with CS2. CS2 did not affect microsomal epoxide hydratase activity, while it increased the measurable activity of UDP-glucuronosyltransferase. The increase was evident 3 hrs after the injection of CS2 in the phenobarbitone pretreated rats. It could also be detected in the control animals 6 hrs after the injection. The present data suggest that the change in the measureble P-450 results from the binding of the metabolite(s) of CS2 to the cytochrome, and its subsequent degradation. The increase in measurable UDP-glycuronosyltransferase activity results probably from the activated perturbation of the structure of microsomal membrane by the metabolites of CS2 in vivo.

Animals↗
PubMed1977

Reduced sulfhydryl groups of rat neurons, glial cells and neurofilaments.

Reactive thiol groups were measured in neurons glial cells and neurofilaments of rat central nervous system. Neurons displayed 27 nmol/mg prot. reactive SH-groups while the figures for glia and neurofilaments were 36.5 and 44 nmol, respectively. For comparison, brain and spinal cord homogenates contained 3.2 and 6.9 nmol/mg of prot. extractable free thiol residues.

Animals↗
PubMed1977

Styrene and acrylonitrile induced depression of hepatic nonprotein sulfhydryl content in various rodent species.

Adult female mice, male rats, female hamsters and male guinea pigs received various doses of styrene (150-1000 mg/kg of body weight) and acrylonitrile (20-80 mg/kg of body weight) intraperitoneally. Both styrene and acrylonitrile caused a depression of the hepatic nonprotein sulfhydryl content. Mouse was the most vulnerable and rat the most resistant species to the effect of both of these two important plastic monomers.

Acrylonitrile↗
PubMed1977

Neurochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Wistar and Gunn rats.

Normal Wistar, heterozygous and homozygous Gunn rats were killed one week after a single intragastric dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 20 microgram/kg in acetone-olive oil. Control animals were treated similarly but without TCDD. The brain protein and RNA content were measured together with enzyme assays of lysosomal acid proteinase and soluble DT-diaphorase. Acid proteinase activity was increased in the brains of the normal Wistar rats after TCDD treatment. RNA and protein contents were lowered in the heterozygous Gunn rats whereas no changes were detected in the homozygous Gunn rats. The cerebral soluble DT-diaphorase activity was slightly enhanced (about 35%) by TCDD treatment only in normal Wistar rats. Our results may point at modified neurotoxic effects of TCDD in chronic exposure to bilirubin as in the case of Gunn rats.

Animals↗
PubMed1976

High binding of CS2 sulphur in spinal cord axonal fraction.

The binding of carbon disulphide sulphur was studied in the spinal cord and its axons of four control and four phenobarbitone pretreated adult rats 3 and 6 h after an intraperitoneal injection of 650 mumol of CS2 in olive oil. The binding of CS2 carbon was measured in the same fractions of two adult control rats 4.5 h after a similar administration of 1.3 mumol of the compound for reference. The specific binding of sulphur was highest in the axons of control animals 3 h after the injection while binding was 17.5% smaller in the axons of phenobarbitone treated animals. The uptake of sulphur was higher in the spinal cord homogenate of the pretreated animals in comparison to control rats. Sulphur was removed from the axonal fraction at a rate of 5.1 natoms/mg of protein/h. Phenobarbitone treatment increased the disappearance of sulphur in the control animals while the rate in the treated rats was 4.9 natoms/mg of protein/h. Phenobarbitone treatment increased the disappearance of sulphur in the spinal homogenate from the removal rate of 0.22 natoms/mg of protein/h in control animals to 0.37 natoms/mg of protein/h in treated rats. The binding of CS2 carbon was negligible 4.5 h after the injection in the axonal fraction. The present data indicate that the release and binding of CS2 sulphur may be responsible for the toxic neural manifestations in chronic CS2 poisoning.

Animals↗