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S Yannai

Publications and source records attributed to S Yannai.

At least 37 records · Page 2Linked to original sources

Effect of inorganic mercury on in vitro placental nutrient transfer and oxygen consumption.

The effect of mercury (HgCl2) on placental amino acid and glucose transfer as determined by the use of their nonmetabolizable radioactive analogues, aminoisobutyric acid (AIB) and 3-o-methyl glucose (3MG), respectively, was studied in an in vitro perfusion model of a term human placenta. Hg2+ was found to decrease the transfer and accumulation of AIB without affecting 3MG transfer. It was also found to decrease the placental oxygen consumption rate. Placental circulation and tissue morphology remained intact, as demonstrated by the antipyrine transfer rate, and by electron microscopy, respectively. The mechanism by which Hg2+ may interfere with placental amino acid transfer and accumulation is discussed. Although much higher concentrations than those found in the ordinary polluted environment were used, this is the first report showing that Hg2+ interferes with an essential human placental function in a system employing a whole human placental cotyledon. This finding may indicate the possible involvement of Hg2+ in impaired organogenesis in early pregnancy or deranged fetal growth during the last trimester.

3-O-Methylglucose↗

In vitro effect of mercury on enzyme activities and its accumulation in the first-trimester human placenta.

The effect of incubating young placental explants with HgCl2 on the activities of aryl hydrocarbon hydroxylase (AHH) (a phase I enzyme), quinone reductase (QR), catecholamine-O-methyltransferase (COMT) (both phase II enzymes), and glucose-6-phosphate dehydrogenase (G-6-PD) is described. Mercury (Hg) at low doses significantly elevated placental phase I and phase II enzyme activities, but decreased the activity of G-6-PD. The increase in activities, which was time- and dose-dependent, was higher in explants incubated for 24 hr than in those incubated for 6 hr. The decrease in placental G-6-PD activity was drastic at low Hg dose levels but at higher levels the inhibitory effect was milder for both incubation periods. Placental explants accumulated Hg in amounts proportional to its concentration in the incubation medium and this accumulation was greater in explants incubated for 24 hr. The data suggest that contamination with low Hg levels from the environment during pregnancy may affect placental enzymatic activity. The accumulation of Hg during short incubation indicates a strong placental cell affinity for Hg, which could affect its other metabolic functions. The system used in sensitive, as it shows alteration in enzyme activity even with relatively low concentrations of the metal and the response is dose-related.

Analysis of Variance↗

The influence of mercury on the secretion of human chorionic gonadotropin in superfused young placental tissue.

The effect of mercury (Hg), as HgCl2, in levels ranging from 0.75 to 12 micrograms/ml medium, on the secretion of human chorionic gonadotropin (hCG) was examined in first-trimester placental explants, after 6 or 24 hr incubation, employing both static and dynamic systems (the latter by superfusion). Later the unbound Hg was washed for 45 min. with fresh medium devoid of Hg, followed by superfusion with the latter medium for 75 min., during which time samples were collected for hCG assay. For the superfusion experiments the parameters used for evaluating the hCG secretion pattern were: mean peak amplitude, pulse frequency and the area under the hCG secretion curve (AUC). The results observed after 24 hr incubation indicate that in the dynamic system the hCG secretion increased significantly, and this increase was dose-dependent. There was also a dose-related increase in mean total hCG secreted by the explants exposed to Hg. Maximal hCG secretion was observed after 24 hr exposure of explants to 6 micrograms of the metal/ml. Both the mean peak amplitude and AUC parameters showed a statistically-significant increase for this dose level. At 12 micrograms/ml, the pulsatile secretion of hCG decreased, but the value for the mean hCG secretion was still higher than that observed for 0.75 and 3 micrograms/ml. After 6 hr incubation, however, there were no significant changes from the control, as judged by all of the above parameters. The levels of hCG secreted by the explants into the media in the static system were not significantly different from their respective controls, for both incubation periods and Hg levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

Enzyme activities in the term human placenta: in vitro effect of cadmium.

The effect of cadmium (Cd) as CdCl2 on some placental enzyme activities were studied after explants had been incubated with the salt for 6 or 24 hr. The results indicated that, for both incubation periods, Cd at low doses had a stimulatory effect on aryl hydrocarbon hydroxylase (AHH) (a phase I enzyme) and on quinone reductase and catecholamine-O-methyltransferase (COMT) (both phase II enzymes). This effect was dose- and time-dependent. Only the activities of AHH and COMT showed a biphasic response, (i.e., increases at the lower dose levels and decreases with the higher ones), whereas that of quinone reductase continually increased with all the dose levels of the metal administered. Glucose-6-phosphate dehydrogenase (G-6-PD) activity was found to be inhibited at all the dose levels of Cd tested, the effect also being time- and dose-dependent. In conclusion, it appears that the use of placental explants can serve as a valuable means for studying the toxic effects of certain xenobiotics, as reflected in the activity of various important enzymes.

Analysis of Variance↗

Transfer and accumulation of cadmium, and the level of metallothionein in perfused human placentae.

The purpose of the present study was to investigate the effect of perfusion with a medium containing 12 or 24 micrograms Cadmium (as CdCl2) per ml on this metal's accumulation, transfer rate and metallothionein (MT) level. The experiments were performed with an isolated lobule of a dually-perfused human term placenta. Placental cell integrity and viability were characterised by their morphology and metabolic function, manifested in the tissue's electron microscopic structure and glucose and oxygen (O2) consumption, respectively. Perfusion with 24 micrograms Cd/ml medium for 5 h resulted in significant elevation in MT. The transfer rate of Cd to the fetal side of the placenta was very slow, and not until 40 min after the addition of Cd into the maternal side was a significant increase in the metal's level observed in the fetal perfusate. Thereafter, the level of the metal increased gradually and reached a steady state about 1 h later, at a level which was less than 1/20th of its concentration in the maternal perfusate. There was a 60-fold increase in Cd level in the cytosolic fraction obtained from the Cd-treated samples. At 12 micrograms Cd/ml no significant changes were noted in morphology, metabolic function and MT content. None of the Cd levels caused a significant change in O2 and glucose consumption, in spite of the fact that with the higher Cd dose the microstructure of the tissue showed some pathological changes. The observed elevation in MT may provide the fetus some protection against the harmful effects of the metal.

Cadmium↗

In vitro effect of mercury on aryl hydrocarbon hydroxylase, quinone reductase, catecholamine-O-methyltransferase and glucose-6-phosphate dehydrogenase activities in term human placenta.

The effect of HgCl2 on human term placental aryl hydrocarbon hydroxylase (AHH), quinone reductase (QR), catecholamine-O-methyltransferase (COMT), and glucose-6-phosphate dehydrogenase (G-6-PD) enzyme activities was studied after incubation of placental explants with the salt for either a 6 or 24 hr period. Mercury (Hg) increased the activities of AHH, QR and COMT, but decreased that of G-6-PD. The increases in enzyme activities, as well as the decrease in G-6-PD activity observed were in all cases time- and dose-dependent. The data suggest that Hg exerts an enhancing effect on the activity of placental phase I enzyme (AHH) and phase II enzymes (QR and COMT). This enhancement may be due to increased de novo synthesis, elimination of some suppressing agent(s), or the decreased breakdown of enzyme protein. Also, the inhibitory effect of Hg on G-6-PD activity appears to indicate that this enzyme is appreciably more sensitive to Hg than the other three enzymes. These findings may imply increased cellular resistance to Hg toxicity. The altered state of activity may also be used as a tool for monitoring exposure to this metal.

Aryl Hydrocarbon Hydroxylases↗

Effects of dietary supplementation with vitamin E, riboflavin and selenium on central nervous system oxygen toxicity.

We attempted to modify the resistance of rats to hyperbaric oxygen (HBO)-induced central nervous system (CNS) toxicity, by increasing the tissue antioxidant potential through dietary factors. Groups of rats were fed excesses of vitamin E (VIT E) alone or in combinations with riboflavin (RIB), selenium (Se) or both, for 30 days. A control group was maintained on an unsupplemented diet. On the 23rd day animals to be exposed were implanted with chronic electrodes for electrocorticographic (ECoG) recording. Later, each group was divided into two subgroups, of which one was exposed to 4.5 atmospheres absolute (ATA) of 100% oxygen (O2) for 30 min., hereafter referred to as "exposed", noting the time of appearance of first electrical discharge (FED) in their ECoG. The remaining subgroups were left unexposed. Forty-eight hours later, all animals were sacrificed and some of their tissues were analyzed for glutathione (GSH). The GSH level in the liver, brain, lungs and blood of all experimental subgroups were significantly higher than in the control unexposed counterparts. Combinations of RIB and/or Se with VIT E failed to show a greater increase in GSH over VIT E alone. This increase was, however, not accompanied by a meaningful delay in the appearance of FED. Forty-eight hours post-exposure, the brain GSH levels of all exposed subgroups were still lower than the respective pre-exposure levels. Yet, in the treated exposed subgroups the GSH levels observed 48 hr after exposure were already higher than in the untreated unexposed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transformations of inorganic mercury by Candida albicans and Saccharomyces cerevisiae.

Saccharomyces cerevisiae and Candida albicans were incubated with 0.25, 0.5, or 0.75 micrograms of Hg (as HgCl2) per ml of Nelson's medium in the presence of trace amounts of oxygen at 28 degrees C for 12 days. Two control media were used, one without added Hg and one without yeast inoculum. Yeast cell growth was estimated after 1, 2, 3, and 8 days of incubation. The contents of organomercury in the system and of elemental mercury released from the media and collected in traps were determined at the end of the experiments. The results were as follows. (i) C. albicans was the more mercury-resistant species, but both yeast species failed to grow in the media containing 0.75 micrograms of Hg per ml. (ii) The amounts of organomercury produced by the two species were proportional to the amount of HgCl2 added to the medium. In all cases C. albicans produced considerably larger amounts of methylmercury than S. cerevisiae. (iii) The amounts of elemental Hg produced were inversely proportional to the HgCl2 level added in the case of S. cerevisiae but were all similar in the case of C. albicans. (iv) Neither organomercury nor elemental Hg was produced in any of the control media.

Biotransformation↗

Effects of dietary factors on antioxidant enzymes in rats exposed to hyperbaric oxygen.

To delineate the effect of dietary supplementation with vitamin E (Vit E) alone or in combination with riboflavin (Rib) or selenium (Se) or both, on biological oxidative damage in rat brain and lungs we exposed rats to hyperbaric oxygen (HBO) and measured the activities of glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G-6-PD) prior to or 48 h after exposure. Rats fed the dietary supplements, and a control group maintained on an unsupplemented diet, for 30 d, were each divided into 2 subgroups, of which 1 was exposed to 4.5 absolute atmospheres (ATA) of 100% oxygen for 30 min, hereafter referred to as "exposed". The remaining subgroups were left unexposed. Pre-exposure GSSG-R activity in brain was elevated in all experimentally fed groups (ranging from 23 to 84%) compared with the unexposed control, whereas GSH-Px, G-6-PD and SOD activities were unchanged. The lungs showed significant increases in pre-exposure GSSG-R, ranging from 15 to 28%, and GSH-Px, ranging from 13 to 23%, activities in all the groups fed the supplemental nutrients, except those on Vit E alone. Increases in G-6-PD activity were observed only in those fed supplements of Rib. In most cases exposure to oxygen caused an increase in GSSG-R, GSH-Px and G-6-PD activities. However the increases were higher in the supplemented groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of N-acetyl-cysteine, D-penicillamine and buthionine sulfoximine on glutathione levels and CNS oxygen toxicity in rats.

The effect of glutathione (GSH) synthesis modulators - L-buthionine sulfoximine (BSO), N-acetyl cysteine (NAC) and D-penicillamine (DPA) - on the susceptibility of rat CNS to O2 toxicity was investigated. The animals were given 5% sucrose or 40 mM solutions of BSO, NAC or DPA in 5% sucrose as drinking water for one week and sacrificed prior to or after exposure to 4.5 ATA O2. The GSH content in brain, liver, lung and blood, and the activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PD) and superoxide dismutase (SOD) in brain and lungs were measured. The brain GSH content and the enzyme activities were not changed by any of the drugs. BSO decreased the GSH content in all the other tissues; NAC and DPA treatments increased the GSH content in lungs, blood and/or liver. The CNS toxicity threshold as measured by the time of appearance of first electrical discharge (FED) on ECoG recording was not changed by NAC or DPA, but BSO brought about a significant delay in FED time. It is suggested that increased extracerebral GSH levels do not protect against CNS oxygen toxicity, and that BSO provides some protection, probably via a glutathione-independent mechanism.

Acetylcysteine↗

Extracorporeal complexation and haemodialysis for the treatment of cadmium poisoning. I. Effects of four chelators on the in vitro elimination of cadmium from human blood.

The effect of ethylenediamine tetraacetic acid (EDTA), glutathione (GSH), citrate and 2,3-dimercaptosuccinic acid (DMSA) on the elimination of cadmium (Cd) from human blood, by complexing haemodialysis, was investigated in vitro. A significant increase in elimination rate was observed with all four chelators compared to that observed without chelators. EDTA was found to be the most effective agent, which at a level of 0.01M in the dialysate facilitated elimination of 80% of the blood Cd originally present.

Blood Cells↗

Efficiency of arsenic clearance from human blood in vitro and from dogs in vivo by extracorporeal complexing haemodialysis.

In vitro dialysis using human blood and in vivo extracorporeal haemodialysis trials with dogs, in the presence and absence of various chelating agents, showed that haemodialysis alone facilitated efficient removal of the metal, even in the absence of any of the chelating agents. In vitro haemodialysis for 5 hr without chelating agents caused the removal of 85% of the arsenic (As) added to the blood 1 hr before the beginning of the treatment. Ten-33% of the single dose given to the dogs, were removed into the dialysate during the first treatment and 8-15% during the second. The amounts of As excreted in the urine of dogs given 0.25 mg As/kg b.wt./day for 6 days were 6.8-7.4 mg As/24 hr, while the same amounts of the metal were removed into the dialysate during haemodialysis for 5 hr. This demonstrates the advantage of employing haemodialysis over the conventional treatment for the enhanced removal of As from the body.

Animals↗

Extracorporeal complexation haemodialysis for the treatment of cadmium poisoning. II. In vivo mobilization and removal.

The purpose of this study was to apply our earlier in vitro findings for extracorporeal complexation combined with haemodialysis to in vivo conditions, for the enhancement of cadmium (Cd) removal from dogs. The results showed that ethylenediaminetetraacetic acid (EDTA), glutathione (GSH) and combination of the two agents (EDTA + GSH) facilitated efficient elimination of cadmium. GSH, EDTA and EDTA + GSH treatments brought about the clearance of 2.2, 14.7 and 18.2 micrograms Cd/kg body weight/hr haemodialysis, respectively. Treatment with EDTA + GSH brought about the most rapid extravascular redistribution of the metal.

Animals↗

In vitro effects of cadmium and arsenite on glutathione peroxidase, aspartate and alanine aminotransferases, cholinesterase and glucose-6-phosphate dehydrogenase activities in blood.

The activity of several blood enzymes in the presence and absence of arsenite (As) and cadmium (Cd) was investigated under in vitro conditions. Both human and rat blood glutathione peroxidase (GSH-Px) activities were adversely affected by As at the 0.8 and 1.6 micrograms/ml levels. The latter was completely inactivated whereas the former retained approximately 30% of its original activity. The effect of Cd on this enzyme was much smaller: 650 g Cd/ml were needed to decrease its activity by 30% of the original value. As noted for GSH-Px, the rat's glutamyl oxaloacetate transaminase (GOT) appears to be appreciably more sensitive to the As inhibitory effect than the human enzyme (by a factor of 3). Cd, however, failed to bring about any inhibition of GOT. In the case of glutamyl pyruvate transaminase (GPT) both As and Cd had a marked effect, manifested in 70% and 78% inhibition, respectively. Blood glucose-6-phosphate dehydrogenase (G-G-PD) was inhibited by both Cd and As, however, within the concentration range used, only Cd inhibited it completely. Cholinesterase (ChE) activity was inhibited completely by both Cd and As.

Alanine Transaminase↗

Effects of divicine, one of its degradation products and hydrogen peroxide on normal and pre-treated rat erythrocytes.

The effects of divicine (DV), one of its degradation products ("blue DV"), and H2O2 on normal and pre-treated rat erythrocyte (RBC) reduced glutathione (GSH) content, spontaneous hemolysis at different tonicity levels, optical absorption spectrum of the hemolysate, as well as on their morphology were investigated. The influence of experimental conditions (temperature, pre- and post-treatment incubation period, presence and absence of glucose in the medium, aerobic and anaerobic conditions and levels of DV and "blue DV") were also studied. Only DV caused a marked decrease in GSH, which is regenerated when the DV level is below 4mM, and in the absence of glucose the regenerating capacity is abolished. DV and "blue DV" not only failed to induce hemolysis but they actually increased the cells' resistance to it; especially "blue DV", which probably lacked GSH-depressing effect. DV caused changes in the absorption spectrum of the hemolysate and to some extent in that of a purified hemoglobin solution, whereas "blue DV" and H2O2 did not. DV also produced profound and long-lasting morphologic changes in the RBC.

Animals↗

Gossypol in cottonseed products: toxicology and inactivation.

The little attention given to the potential of cottonseeds as food for monogastric animals and man is due to the presence of toxic principles in them, especially gossypol. The injury to livestock associated with ingestion of cottonseeds results from the unfavorable physiological effect of gossypol per se, as well as from its adverse effects on the protein nutritive value of the food (mainly by rendering lysine metabolically unavailable). Various approaches have been employed to overcome these problems, by removing the gossypol glands, growing glandless varieties, extraction of gossypol with solvents, or through inactivation by heat processing, reacting with cations or with certain organic compounds. In this study the phospholipid fraction (gums) derived from soybeans, which is relatively rich in phospholipids containing a free amino group, was used with a view to lowering the tendency of gossypol to bind with lysine, and at the same time to inactivate the gossypol by converting it into a bound form. Dehulled and flaked cottonseeds were mixed with 5% soybean gums and 0.5% NaOH, in a laboratory cooker resembling the apparatus used in the cottonseed processing industry. The meat was cooked for different periods and at several temperatures. Later the oil was extracted with hexane and the meal was tested for free gossypol, "available lysine" and protein nutritive value, in comparison with a control batch treated similarly but without gums. The results proved the superiority of the meal treated with gums, as evidenced by all the above parameters.

Animals↗

Toxicological evaluation of a liquid fraction derived from palm oil.

The possible toxicity and mutagenicity of a heated liquid fraction derived from palm oil by transesterification was tested with rats fed diets containing 15% of the oil and by various in vitro and chemical assays on the animals sera. No adverse effects of any kind were noted in the animals fed diets containing a high level of the oils, and the Ames Test failed to reveal a mutagenic potential in any of them. The chemical tests did not show any noteworthy undesirable changes, either.

Acetylcholinesterase↗

Conversion of inorganic lead into a highly-toxic organic derivative by marine microorganisms.

It has been reported that certain microorganisms isolated from lake sediments may transform inorganic lead compounds to organic derivatives, which are by at least one order of magnitude more toxic than the parent (inorganic) compounds. The purpose of this study was to investigate whether microorganisms isolated from a marine sediment could also produce such metabolites in an in vitro system simulating the marine ecosystem. The experimental setup included: 1) A sterile control system containing added inorganic lead (referred to as Pb2+); 2) a nonsterile control system without added Pb2+; 3) a nonsterile experimental system containing added Pb2+. The amount of added Pb2+ ranged from 5 to 1,000 ppm. Aliquots were taken at different intervals from the nonsterile systems and the surviving microorganisms were identified and counted. The main results were as follows: 1) The higher lead levels were toxic to all microorganisms. 2) Organic lead was only detected in the nonsterile experimental system, apparently due to microbial action, since none was found in the sterile systems. 3) Several bacteria exhibiting various degrees of tolerance for lead were isolated.

Aerobiosis↗