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S H Sterri

Publications and source records attributed to S H Sterri.

17 recordsLinked to original sources
PubMed1987

Carboxylesterases in guinea-pig plasma and liver. Tissue specific reactivation by diacetylmonoxime after soman inhibition in vitro.

The carboxylesterase activity in both plasma and liver of guinea-pig were separated into three main peaks by chromatofocusing. Two of the three plasma enzymes were retained by affinity chromatography on Affi-Gel Blue (100-200 mesh). Isoelectric points determined by chromatofocusing or isoelectrofocusing were pI 6.1, pI 5.2 and pI 4.0 for the plasma enzymes, and pI 5.7, pI 5.2 and pI 4.5 for the liver enzymes. The effect of selective esterase inhibitors, soman, physostigmine (cholinesterase inhibitor) and bis-4-nitrophenyl phosphate (carboxylesterase inhibitor), suggested that the three enzymes in both tissues may be regarded as carboxylesterases. However, the pI 5.7 carboxylesterase was partially inhibited by physostigmine, and the pI 4.5 carboxylesterase was almost not affected by bis-4-nitrophenyl phosphate. The ratio between the activities towards 4-nitrophenyl butyrate and methyl butyrate differed among the carboxylesterases in both tissues. All three carboxylesterases in plasma were partially reactivated by diacetylmonoxime after soman inhibition in vitro, but to a different extent. The soman inhibited liver carboxylesterases were not reactivated by diacetylmonoxime.

Animals↗
PubMed1985

A method for generating toxic vapors of soman: toxicity of soman by inhalation in rats.

A method for administration of highly toxic chemicals by inhalation was developed. The model has three features of special interest: (1) a diffusion cell for producing a constant gas concentration, if necessary for several hours and days, (2) a small rapidly equilibrated inhalation chamber (1100 ml), and (3) complete isolation of the toxic chemicals from the atmosphere. The LCt50 of the anticholinesterase soman [o-(1,2,2 trimethylpropyl)-methyl-phosphonofluoridate] was 400 mg min/m3, registered 24 hr after the end of exposure. The lethal concentration X time of soman was 520 +/- 60 mg min/m3 when exposing the animals until death in the inhalation chamber. The exposure was less than 30 min and the concentration of soman was 21 mg/m3. The inhibition of acetylcholinesterase, cholinesterase, and carboxylesterase activities in different tissues was analyzed to study the possible barrier mechanisms that might exist in the body to soman. There was a large inhibition of the carboxylesterase and cholinesterase activities in bronchi and lungs as well as in blood. Carboxylesterases were important as detoxifying enzymes, as shown by 70% enhancement in toxicity of soman following sc pretreatment with TOCP (tri-ortho-cresyl-phosphate), a carboxylesterase inhibitor.

Acetylcholinesterase↗
PubMed1985

A radiochemical assay method for carboxylesterase, and comparison of enzyme activity towards the substrates methyl [1-14C] butyrate and 4-nitrophenyl butyrate.

A radiochemical assay for carboxylesterase based on the substrate methyl[1-14C]butyrate is described. The blank value corresponds to 1.04 micrograms (liver)-1.44 mg (plasma) of tissues with the highest and lowest activity respectively, which constitute the sensitivity of the method. The hydrolysis of methyl butyrate and 4-nitrophenyl butyrate by plasma, liver, lung, heart, diaphragm, cerebrum, kidney and duodenum of rat have been compared. The results showed that the two substrates were hydrolysed preferentially by two different groups of the enzyme. The effect of selective esterase inhibitors showed that both groups can be characterized as carboxylesterase, because bis-4-nitrophenyl phosphate inhibits the hydrolysis of both substrates, physostigmine has only a slight effect and EDTA is no inhibitor. The exception is the enzyme in the duodenum which is inhibited by all three inhibitors. The effect of phenobarbital induction and soman treatment on enzyme activity towards the two substrates were similar. Sex difference in the plasma activity towards methyl butyrate, but not 4-nitrophenyl butyrate, indicates that the group of carboxylesterase preferentially hydrolyzing 4-nitrophenyl butyrate may be the most important for the detoxification of soman.

Animals↗
PubMed1985

Carboxylesterases, importance for detoxification of organophosphorus anticholinesterases and trichothecenes.

Several different types of experiments, including the use of inhibitors, have shown that carboxylesterases are a major factor in the metabolism and therefore detoxification of organophosphorus compounds such as soman and trichothecene toxins. The development of a new assay method for the enzyme has allowed us to separate the carboxylesterases into two major groups. The carboxylesterases can, however, be further separated by gel filtration, affinity chromatography, isoelectric focusing, and chromatofocusing into several isoenzymes. Liver microsomal carboxylesterases can be separated into five or six isoenzymes whereas guinea-pig plasma contains two isoenzymes. The isoenzymes differ in molecular weights, isoelectric points, substrate specificities, and affinity for inhibitors. Intravenous administration of a carboxylesterase preparation lowered the toxicity of soman in young rats. Carboxylesterases from rat and guinea-pig plasma inhibited by soman could be reactivated by DAM, whereas enzymes from porcine liver were not reactivated. Only one of the isoenzymes from rat liver microsomal preparation was responsible for the metabolism of T-2 toxin to HT-2. The further metabolism of HT-2 was performed by esterases from rat liver cytoplasma. Long-term exposure of the bronchial muscle to low concentration of soman modulate the bronchial contraction.

Animals↗
PubMed1985

Esterase activities and soman toxicity in developing rat.

The activity of carboxylesterase and cholinesterase in plasma, liver and lung of young rats at different ages (5-31 days old) have been measured. The cholinesterase activity in the tissues of both sexes were almost constant during the development, and were similar to adult male activity. The carboxylesterase activity towards methyl butyrate and 4-nitrophenyl butyrate in plasma of both sexes increased from negligible (5 days old) to adult male value (31 days old). The carboxylesterase activities in liver increased markedly during the period, whereas the lung activities increased only slightly. The toxicity of soman was 6-7 fold higher in 5 days old rats compared to 30 days old rats. The decrease in toxicity correlated well with the increase in plasma carboxylesterase.

Aging↗
PubMed1982

Reduction of blood cholinesterase activities following administration of soman by different routes in guinea-pig.

The inhibition of erythrocyte acetylcholinesterase activity following intravenous, intraperitoneal, subcutaneous, or percutaneous administration of sublethal doses of soman in guinea-pig has been investigated. The inhibition was found to be almost completed within 1 min., 20 min., 60 min. or 90-120 min. respectively, the inhibition rates were of first order, and half-lives were dose dependent. The possibility of storage of soman after administration of sublethal doses was also examined by the injection of electric eel acetylcholinesterase. It is concluded that there is very little, if any, storage of free soman in the organism after injection of sublethal doses of soman.

Acetylcholinesterase↗
PubMed1981

Toxicity of soman after repetitive injection of sublethal doses in guinea-pig and mouse.

Injection of sublethal doses of soman in guinea-pig and mouse subcutaneously every 3.5, 8, 12 or 24 hours led to cumulative LD50 doses which were markedly higher than the acute one. When animals were exposed every 24 hrs to half LD50 doses of soman, a majority of guinea-pigs but relatively few mice, survived a total exposure of 5-6 times the acute LD50 dose. Guinea-pig brain and diaphragm acetylcholinesterase activities declined steadily during the repeated soman exposure. Plasma cholinesterase activity was less than 10% 1 hr after soman injection, but was restored to 40-50% of control within 24 hrs. Liver aliesterase activity was not significantly inhibited by soman, whereas plasma aliesterase activity was 70% inhibited after 1 hr and restored to control level within 24 hrs. TOCP treatment of guinea-pig led to 3-fold increase in acute soman toxicity, and reduced their tolerance from more than 6 lD50 to 2.5 LD50 dose of soman. It is included that the recovery of plasma aliesterase and cholinesterase play an important part in the observed tolerance towards repeated soman treatment.

Acetylcholinesterase↗
PubMed1981

Factors modifying the toxicity of organophosphorus compounds including dichlorvos.

The effect of repetitive doses of organophosphorus agents in experimental animals has been studied. The cumulative LD50 dose depended upon the time interval between injections of toxic agent. From these data it was possible to obtain the rate of detoxification of these agents. In the case of soman and sarin TOCP pretreatment, an inhibitor of plasma aliesterase, modified both the acute LD50 and the rate of detoxification. The results therefore suggest that recovery of plasma aliesterase contributes to a large extent in detoxification of chronically administered soman and sarin. In contrast, tolerance to chronically administered dichlorvos can not be correlated to recovery of plasma aliesterase, but correlates well with a rapid spontaneous reactivation of acetylcholinesterase.

Acetylcholinesterase↗
PubMed1980

Acetyl-CoA synthesizing enzymes in cholinergic nerve terminals.

The activities of five enzymes involved in acetyl-CoA synthesis, pyruvate dehydrogenase complex, ATP citrate lyase, carnitine acetyltransferase, acetyl-CoA synthetase, and citrate synthase, were determined in normal nucleus interpeduncularis and nucleus interpeduncularis in which cholinergic terminals were removed following lesion of the habenulointerpeduncular tract. The activities of aspartate transaminase, fumarase, and GABA transaminase also were determined to compare the effect of lesion on other mitochondrial enzymes which are not linked to the biosynthesis of ACh. In normal nucleus interpeduncularis the activities of carnitine acetyltransferase and pyruvate dehydrogenase complex were higher than the activity of ChAT (choline acetyltransferase), whereas the activities of acetyl-CoA synthetase and citrate synthase were considerably lower than that of ChAT. The effect of the lesion separated the enzymes into two groups: the activities of pyruvate dehydrogenase complex, carnitine acetyltransferase, fumarase and aspartate transaminase decreased by 30--40%, whereas the activities of the other enzymes descreased 5--15%. ChAT activity was in all cases less than 15% of normal. It could be concluded that none of the acetyl-CoA synthesizing enzymes decreased to the degree that ChAT did. Only pyruvate dehydrogenase complex and carnitine acetyltransferase seem to be localized in cholinergic terminals to a significant degree. ATP citrate lyase as well as acetyl-CoA synthetase seem to have less significance in supporting acetyl-CoA formation in cholinergic nerve terminals.

4-Aminobutyrate Transaminase↗
PubMed1980

Toxicity of soman after repetitive injection of sublethal doses in rat.

Injection of sublethal doses of soman in rat intraperitoneally or subcutaneously every 4, 8, 12 or 24 hours led to chronic LD50 doses which were markedly higher than the acute one. When rats were exposed every 24 hrs to half LD50 doses of soman, several of the animals did not show symptoms of soman poisoning and survived a total exposure of 4-7 times the acute LD50 dose. Brain and diaphragm acetylcholinesterase activities declined steadily during the chronic soman exposure. The so-called external acetylcholinesterase activity of the diaphragm was inhibited to a slightly less degree than the total acetylcholinesterase of the same tissue. The ability of the liver to hydrolyze soman was similar in rats which survived several 24 hr doses and untreated rats.

Acetylcholinesterase↗
PubMed1979

Effect of toxogonin and P2S on the toxicity of carbamates and organophosphorus compounds.

Toxogonin (80 mg/kg intraperitoneally) given 15 min. prior to the administration of organophosphorus insecticides dimethoate, malathion, parathion and azinphos-methyl, organophosphorus warfare agents soman and tabun, or carbamates physostigmine, pyridostigmine and aldicarb, reduced the toxicity in mice of these agents by increasing their LD50 dose 1.5-3 fold. The toxicity of the carbamate insecticide carbaryl, however, was significantly increased by toxogonin. Similar results were obtained for P2S (150 mg/kg intraperitoneally) with respect to the toxicity of dimethoate, soman and pyridostigmine, whereas no effect could be detected on the toxicity of tabun. Only a slight reduction in the toxicity of physostigmine was observed. The acetylcholinesterase activity in erythrocytes, cerebrum and diaphragm of surviving mice 20 hours after organophosphate intoxication was similar both in toxogonin and P2S treated animals and untreated animals.

Animals↗
PubMed1978

Isolation of organic anions by extraction with liquid anion exchangers and its application to micromethods for acetylcholinesterase and 4-aminobutyrate aminotransferase.

Organic anions of particular importance to biochemistry such as Krebs cycle intermediates, glycolysis intermediates, simple fatty acids, adenine nucleotides and CoA derivatives can be quantitatively extracted from a buffered solution by high-molecular-weight ammonium salts in an organic solvent. Phosphate salts of tertiary amines in chloroform were the most efficient extractants. The isolation procedure was found to be an example of amine neutralization. The effect of pH, different inorganic anions, volume ratios between the two phases, concentration of the isolated anions and concentration of the ammonium salts have been investigated. The extraction technique has been applied to rapid and sensitive radiochemical methods for the determination of acetylcholinesterase and 4-aminobutyrate aminotransferase activities.

4-Aminobutyrate Transaminase↗