Correction with formate of metabolic disorders in alcoholic intoxication

Formate was studied for its effect on the content of acetaldehyde, activity of the total aldehyde dehydrogenase, content of substrates of glycolysis and tricarbonic-cycle and pool of free amino acids of rat tissues during alcohol intoxication. The introduction of formate during the acute alcohol intoxication lowers the acetaldehyde content in the blood; the ethanol load being prolonged--it increases the activity of aldehyde dehydrogenase and normalizes the content of pyruvate, glutamate and malate in the liver and glutamate and oxaloacetate in the brain, that evidences for the correction of metabolic disturbances in the organism.     

Transition between Acute and Chronic Hepatotoxicity in Mice Is Associated with Impaired Energy Metabolism and Induction of Mitochondrial Heme Oxygenase-1

The formation of protein inclusions is frequently associated with chronic metabolic diseases. In mice, short-term intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) leads to hepatocellular damage indicated by elevated serum liver enzyme activities, whereas only minor morphological changes are observed. Conversely, chronic administration of DDC for several weeks results in severe morphological damage, characterized by hepatocellular ballooning, disruption of the intermediate filament cytoskeleton, and formation of Mallory-Denk bodies consisting predominantly of misfolded keratins, Sqstm1/p62, and heat shock proteins. To evaluate the mechanistic underpinnings for this dichotomy we dissected the time-course of DDC intoxication for up to 10 weeks. We determined body weight change, serum liver enzyme activities, morphologic alterations, induction of antioxidant response (heme oxygenase-1, HO-1), oxidative damage and ATP content in livers as well as respiration, oxidative damage and the presence and activity of HO-1 in endoplasmic reticulum and mitochondria (mtHO-1). Elevated serum liver enzyme activity and oxidative liver damage were already present at early intoxication stages without further subsequent increase. After 2 weeks of intoxication, mice had transiently lost 9% of their body weight, liver ATP-content was reduced to 58% of controls, succinate-driven respiration was uncoupled from ATP-production and antioxidant response was associated with the appearance of catalytically active mtHO-1. Oxidative damage was associated with both acute and chronic DDC toxicity whereas the onset of chronic intoxication was specifically associated with mitochondrial dysfunction which was maximal after 2 weeks of intoxication. At this transition stage, adaptive responses involving mtHO-1 were induced, indirectly leading to improved respiration and preventing further drop of ATP levels. Our observations clearly demonstrate principally different mechanisms for acute and chronic toxic damage.     

Comparison of Effects of Potassium Iodide and Iodosalicylates on the Antioxidant Potential and Iodine Accumulation in Young Tomato Plants

Iodine (I) is classified as a beneficial element for plants. Until now, there have been only hypotheses regarding the uptakes of organic iodine compounds by plant roots. The purpose of our research was to compare the uptakes and effects of the application of the following mineral and organic iodine compounds on young tomato plants: KI, 5-iodosalicylic (5-ISA), and 3,5-diiodosalicylic (3,5-diISA) acids. An additional control combination included the treatment with salicylic acid (SA) alone. All compounds were introduced into the nutrient solution in 5, 10, 25, and 50 μM I concentrations. It was established that after the application of 5-ISA and 3,5-diISA, iodine is taken up to a smaller extent than from KI. The tested KI, 3,5-diISA, and 5-ISA doses had no negative impact on the growth and development of plants, apart from the reduction of shoot biomass after the application of 3,5-diISA in 10 and 25 µM I doses. All applied compounds, except for SA, caused a reduction of ascorbic acid (AA) content and increase of dehydroascorbic acid (DHA) content in leaves. A significant increase of APX activity was noted only for the highest doses of KI and 5-ISA. None of the iodine compounds, in most tested doses, have substantially increased the CAT and POX activities in tomato leaves. Application of KI decreased the levels of all analyzed sugars in tomato leaves. The effect of iodosalicylates on sugar content varied depending on the compound: when applied in the highest dose 5-ISA increased, while 3,5-diISA decreased the sugar accumulation in tomato plants. In all tested treatments, a reduction of SA content in leaves was noted. We conclude that organic iodine compounds, i.e., 3,5-diISA and 5-ISA, can be taken up by the roots of tomato plants at an early stage of development.

     

Effect of alcohol intoxication on ascorbic and dehydroascorbic acid levels in rat tissue. and human blood

It is found that acute ethanol intoxication is accompanied by a decrease in the ascorbic acid content in the brain, liver and kidneys. The content of dehydroascorbic acid in kidneys in this case increases and in the brain tends to decrease. The chronic alcohol intoxication of rats has an opposite (as compared to the acute intoxication) effect on changes in the content of ascorbic and dehydroascorbic acids in the studied organs. People with chronic alcohol intoxication have the lower content of ascorbic acid in blood plasma and the higher content in erythrocytes, the content of dehydroascorbic acid being increased.     

Modifications of liver content of cyclic nucleotides in the rat poisoned with white phosphorus]

In rat liver following white phorphorus poisoning a biphasic increase in cyclic AMP concentration was observed. After a lag period of 1 hour the cyclic AMP content rose to a first peak at 4 hours and to a second peak at 12 hours of intoxication. The cyclic AMP level fell to normal after 24 hours, by which time the cyclic nucleotide concentration was approaching control values. On the contrary, cyclic GMP content was found to the normal level during the different stages of intoxication. Only at 36 hours the cyclic GMP amount appeared significantly increased above the control values. Serum activity of alanine- and aspartate-amino transferases was found changed from 8 hours to 24 hours after poisoning. The serum level of the two enzymes was overlapping the control values after 36 hours. These results are discussed in relation to hepatocyte necrosis following white phosphorus intoxication.     

Quantitative autoradiographic analysis of muscarinic receptors and quantitative histochemistry of acetylcholinesterase in the rat brain after trimethyltin intoxication

The influence of trimethyl tin (TMT) intoxication on muscarinic cholinergic receptors and histochemistry of acetylcholinesterase (AChE) in the rat brain 21 days after treatment was studied. The topographical distribution and reduction in muscarinic receptor sites were analysed by means of quantitative receptor autoradiography using [³H]quinuclidinyl benzilate (QNB). TMT treatment produced a decrease in cholinergic receptors in a large number of brain regions.

The quantitative distribution of AChE was examined in over 60 regions following TMT intoxication. The activity of AChE was significantly affected. Reduced AChE content was found in several brain regions following TMT intoxication. The effect on AChE content was confined to cholinergic terminal areas, e.g. the hippocampus, while in the area dentata a significant increase in AChE content was detected.

The results are interpreted in terms of TMT producing disruption of the cholinergic system with implications for a neuroanatomical basis of impaired memory mechanisms.     

Lipid peroxidative damage on cadmium exposure and alterations in antioxidantsystem in rat erythrocytes: A study with relation to time

Cadmium induced lipid peroxidation (LPO) and the activity of antioxidantenzymes after the administration of a single dose of CdCl 2 (0.4 mg kg body wt, ip) was studied in rat erythrocytes.Cd intoxication increased erythrocyte LPO along with a decrease insuperoxide dismutase (SOD) up to three days of Cd treatment. Thedecrease in erythrocyte catalase (CAT) activity was marked within9 h of Cd intoxication. After three days of Cd treatment, LPOdecreased towards normal, along with an increase in erythrocyteSOC and CAT activity. Blood glutathione (GSH) decreased significantlywithin 24 h of Cd treatment, followed by an increase towards normal.Erythrocyte glutathione S-transferase (GST) activity increased up to10 days of Cd intoxication, probably in an attempt to reduce Cd toxicity.Serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase(SALP) and serum bilirubin increased up to 10 days of Cd intoxication.Blood urea increased significantly up to three days, followed by a decreasetowards normal. The results show that Cd induced LPO was associated with adecrease in antioxidant enzymes and GSH in erythrocytes; as these antioxidantsincrease in erythrocytes with recovery from Cd intoxication, the Cd inducedLPO reversed towards normal. The increase in the SGPT, SALP and serum bilirubincorrelated with LPO. The results suggest that Cd intoxication induces oxidativestress and alters the antioxidant system, resulting in oxidative damage torat erythrocytes. © Rapid Science 1998     

The activity of 2',5'-oligoadenylate-synthetase in rat spleen lymphocytes in the chronic ethanol intoxication and administration of zinc acetate

It was shown that the activity of interferon-induced enzyme 2',5'-oligoadenylate-synthetase is suppressed in rat spleen lymphocytes under the chronic alcohol intoxication. The values of enzyme activity were minimal under the long-term action of etanol (21 day). The combined administration of zinc acetate and etanol to rats causes the increase of enzyme activity, the effect is most expressed on the late stages of alcohol intoxication development.     

Carbohydrate, protein and glycoprotein metabolism by the guinea-pig liver in chronic metribuzin poisoning

Male guinea-pigs weighing 400-600 g, 8 months old, were given metribuzin directly into the gastric lumen over a period of 30 days (20 animals) or 90 days (20 animals) 6 times a week. In the liver of the poisoned animals, the glycogen level and the AspAT and AlAT activities, while in the serum the total protein and the fractions albumin, alpha 1-globulin and gamma-globulin significantly decreased; serum glucose and the serum fractions alpha 2-globulin and beta-globulin, each showed an increase. The glycogen level in the liver, total protein, glucose as well as the alpha 1 and alpha 2 globulin fractions in the serum showed not appreciable difference between 30 and 90 days of intoxication. After 90 days of metribuzin treatment AspAT and AlAT dropped in the liver and rose in the serum, in comparison to the 30-day values. As to the parameters of glycoprotein metabolism, the intoxicated animals showed a significant decrease and increase in concentration of hexosamines and sialic acids in the liver and serum, respectively. Metribuzin intoxication also cause a significant decrease in activity of glucosamine phosphate isomerase and significant increase in activity of glycosidases in the liver. The results suggest that metribuzin disturbs the metabolism of carbohydrates, proteins and glycoproteins in the guinea-pig liver.     

Lesions of skeletal muscles in rats with acute alcoholic intoxication

Histological and histochemical studies of the rat skeletal muscles in acute alcohol intoxication have revealed metabolic disturbances, characterized by a decreased glycogen level, small-drop fatty infiltration, decreased activity of aerobic and enhanced activity of anaerobic enzyme glycolysis, dystrophic and focal necrotic myocyte changes. Acute alcohol intoxication in fasting animals is accompanied by more pronounced dystrophic and necrotic myocyte changes, decreased glycogen and lipid content.     

A Possible Role for Taurine in Osmoregulation Within the Brain

Intracranial microdialysis was used to measure changes in extracellular amino acids within the rat brain during local osmotic alteration of the extracellular microenvironment or during systemic water intoxication. Increased cellular hydration produced by either of these methods was accompanied by a marked increase in extracellular taurine levels without affecting the other amino acids measured. With local osmotic alteration, this increase was osmolarity dependent and reversible. The specificity, sensitivity, and reversibility of the increase in extracellular taurine strongly suggest a functional role in osmoregulation in the brain under normal as well as pathological conditions.     

The synthesis and in vitro testing of structurally novel antibiotics derived from acylnitroso Diels-Alder adducts

The structural similarity between beta-lactam antibiotics, such as penicillin, and isoxazolidine-3,5-dicarboxylic acids led to the hypothesis that isoxazolidine-3,5-dicarboxylic acids could be effective analogs of beta-lactam antibiotics. The syntheses of relevant isoxazolidine-3,5-dicarboxylic acids from acylnitroso Diels-Alder adducts and subsequent biological testing have shown that these first examples are inhibitors of Escherichia coli X580.     

Fatty acid composition of lipids in erythrocytes and blood plasma in cadmium intoxication and its correction with unitiol

The effect of cadmium chloride on the fatty acid composition of lipids of the erythrocytes and blood plasma has been studied. It has been established that in the process of cadmium intoxication the decrease of the level of unsaturated fatty acids takes place and the most considerable changes in the content of oleic and arachidonic acids. It makes possible to assume the disturbance of both the erythrocytes membrane structure and metabolism in the erythrocyte. Unitiol injection promotes the normalisation of the indices under investigation.     

Evolution des Teneurs en Acides Chlorogénique et "Isochlorogénique' au Cours du Traitement de Vernalisation des Racines de Cichorium intybus

In a cold-requiring variety of endive (chicory, Cichorium intybus L. ev. Witloof) we could demonstrate a relationship between the variations in the content of chlorogenic acid during the cold treatment of the roots and their disposition to produce flowers in vitro. An increase in the level of chlorogenic acid in the roots preceded the development of their aptitude to form flower buds. In addition, the three main forms of “isochlorogenic’ acid are present in the roots of this cultivar: 3,5-dicaffeoyl-quinic acid, 3,4-dicaffeoyl-quinic acid, and traces of 4,5-dicaffeoyl-quinic acid. The variations in the levels of chlorogenic and “isochlorogenic’ acids indicate that part of the chlorogenic acid (3-caffeoyl-quinic acid) is converted to 3,5-dicaffeoyl-quinic acid.     

Plasma and liver amino acids in rats after administration of ethanol or acetaldehyde

The changes in the level and pattern of free amino acids in plasma and liver after ethanol or acetaldehyde intoxication has been investigated in rats. After administration of 30% (w/v) ethanol, 6 g kg-1, or 1.5% (w/v) acetaldehyde, 0.3 ml kg-1, for 4 weeks we found a decrease in plasma and liver branched-chain amino acids and an increase in plasma aromatic amino acids and methionine. The results are analogous to those found in studies of damaged liver.     

The dose-dependent effect of 3,5-dicarbomethoxyphenylbiguanide on activity of the glutathione antioxidant system in heart and blood serum of rats with experimental myocardial infarction

Administration of a synthetic compound with predicted anti-ischemic and cardioprotective activity, 3,5-dicarbomethoxyphenylbiguanide (3,5-DCMPBG) to rats with experimental myocardial infarction led to a decrease in the lipid peroxidation level, glutathione peroxidase activity, the level of reduced glutathione, activity of NADP-isocitrate dehydrogenase in the heart and blood serum, and activity of glucoso-6-phosphate dehydrogenase in heart in comparison with their levels in untreated animals with myocardial infarction. This may be attributed to a decrease of free radical processes and reduction of antioxidant system loading induced by the protective effect of the administered compound. At the same time the increase glutathione reductase activity observed under these conditions in the heart and blood serum is probably associated with specific influence of 3,5-DCMPBG on this enzyme.     

The role of pi-acidic and pi-basic chiral stationary phases in the high-performance liquid chromatographic enantioseparation of unusual beta-amino acids

The application of 3,5-dimethylphenyl-carbamoylated-beta-cyclodextrin (Cyclobond I 2000 DMP) and 2,6-dinitro-4-trifluoromethylphenyl-ether-beta-cyclodextrin-based (Cyclobond DNP) chiral stationary phases for the high-performance liquid chromatographic enantioseparation of unusual beta-amino acids is reported. The investigated amino acids were saturated or unsaturated alicyclic beta-3-homo-amino acids and bicyclic beta-amino acids. Prior to chromatographic analyses, all amino acids were transformed to N-3,5-dinitrobenzoyl- or N-3,5-dimethylbenzoyl form to ensure a pi-acidic or pi-basic function and to enhance the pi-acidic-pi-basic interactions between analytes and chiral selectors. Chromatographic results are given as retention, separation and resolution factors. The chromatographic conditions were varied to achieve optimal separation. The sequence of elution of the enantiomers was determined in some cases.     

Sexual specificity of change of pancreatic alpha-amylase activity in rats in cadmium intoxication

It was shown that the activity of alpha-amylase in the pancreas tissue, intestine content and blood, as well as kinetic characteristics in different substratum concentration changed in males and females after unitary oral administration of chloride cadmium in the dose 5 mg/kg. It was revealed that, after a single administration of chloride cadmium, growth of the pancreas weight, contents of protein and activity of alpha-amylase in the pancreatic tissue increased with parallel reduction of activity of enzyme in the small intestine. In acute cadmium intoxication, functional reorganizations in the pancreas are identical to initial stages of carcinogenic shifts. Such shifts are more expressed in females in comparison with males, especially after the cadmium intoxication.     

Characteristics of creatine kinase isoenzyme spectrum in the blood of rats in aging and acute alcoholic intoxication

The study of creatine kinase (CK) activity in biological liquids of rats of different age has shown that CK blood activity is decreased in aged rats. Acute alcohol intoxication leads to significant increase of CK blood activity.