Interrelationship between iron deficiency and lead intoxication (part 1)

The influence of lead exposure, iron deficiency, or their combination on certain biochemical parameters in blood, plasma, and urine of rats was investigated in an attempt to identify the specific diagnostic tests of the two conditions and to draw a possible interrelationship between the two factors. The decrease in blood-glutathione peroxidase activity, -packed cell volume, plasma-ceruloplasmin, and-Fe levels and increase in urinary excretion of delta-aminolevulinic acid, plasma-cholesterol, and-total Fe binding capacity occur under Fe deficiency as well as Pb intoxication. However, increase in the activity of blood delta-aminolevulinic acid dehydratase (ALAD) without any change in blood zinc protoporphyrin (ZPP) level appears to be a specific effect of Fe deficiency that could be distinguished from Pb intoxication, a condition characterized by the inhibition in blood ALAD activity accompanied by an increase in blood ZPP level. The linear regression analysis of the data showed that the blood Pb and plasma free cholesterol levels increase with the decrease in plasma Fe level.     

The use of blood plasma with elevated titers of antibodies to Re-chemotype glycolipid in peritonitis

The article analyzes the possibility of immunotherapy of septic complications in cases of peritonitis caused by gram-negative bacteria. A strictly inverse correlation between the severity of intoxication and the level of antibodies to glycolipid Re in blood serum has been established. About 5% of healthy nonimmunized donors have elevated Re-antibody titers (1:128 and higher) in their blood plasma. Screening of blood preparations from more than 1000 donors permitted the creation of the blood plasma bank used for the treatment of peritonitis patients. Immunotherapy of such patients has made it possible to decrease almost two-fold the death rate and to reduce the severity and duration of the intoxication syndrome in patients, as well as to improve the results of the treatment of peritonitis.     

Morphological and biochemical alterations in growing rats induced by etretinate

Etretinate is an aromatic retinoid extensively used on Dermatology. Its toxic effects, however, reduce its application from a clinical point of view. In the present paper, we study etretinate intoxication of 48 growing Wistar rats. The intoxication was for 12 weeks using etretinate doses of 0.5 and 6 (mg/kg)/day. The concentrations of etretinate in plasma and liver were determined. Total seric cholesterol and triglyceride concentrations were analyzed. Structural and ultrastructural histological studies of liver samples were carried out. Continuous etretinate ingestions seem to produce an alteration in the detoxication of enzymatic complexes in the growing rats with both the concentrations, due to the increase in etretinate blood plasma observed during the study. There is a relationship between the etretinate dose and its blood plasma concentration and toxic effect, but there is not with etretinate concentration in the liver. The blood plasma concentration of cholesterol and triglycerides is not related to histological liver lesions. The histological study confirms hepatotoxicity with both doses. Nevertheless, the anatomopathological lesions observed do not seem to be related to the blood plasma and liver etretinate concentrations.     

Effects of pharmacological doses of Vitamin D3 on mineral balance and profiles of plasma Vitamin D3 metabolites in horses

Metabolism and functions of Vitamin D in horses differ from those in humans, pigs and rats. In horses, calcidiol and calcitriol concentrations in blood plasma are remarkably low (<10 nmol L(-1); 20-40 pmol L(-1), respectively). When a toxic amount of Vitamin D(3) is administered, the responsiveness of calcium and calcitriol concentrations in blood plasma is much reduced compared to the other domestic animal species but inorganic phosphate (Pi) response is much more marked, leading to an increase of the Ca x Pi product. Also, soft tissue calcifications have been observed to develop in horses during Vitamin D(3) intoxication. It was suggested that the elevation of the Ca x Pi product may play a causative role in this calcification process. To test this assumption, two horses were treated with 40,000 IU kg(-1) of Vitamin D(3) whilst dietary uptake of Ca and Pi was restricted to prevent or to diminish the increase of the Ca x Pi product. Distribution, number and severity of calcification centres were considerably less in these horses than in the control animals of a previous experiment which had received the same amount of Vitamin D(3) but where Ca and Pi intake was not restricted. It appears from these findings that in horses, the increase of the Ca x Pi product in blood plasma during a Vitamin D intoxication contributes to the soft tissue calcifications. It is further concluded that in the event of a Vitamin D intoxication, it is recommended to restrict the Ca and Pi uptake immediately. The authors believe that this may help to prevent or at least diminish soft tissue calcifications which are often fatal to the horse due to nephrocalcinosis.     

The level of free radical oxidation products in heart and blood plasma in diabetes mellitus combined with chronic alcohol intoxication

The level of glycemia, contents of free radical oxidation products (thiobarbituric acid reactive substances, oxidatively modified proteins) have been investigated in blood plasma and heart of rats with diabetes mellitus subjected to chronic alcohol intoxication. Preexisting diabetes mellitus had no influence on the effect of chronic alcohol consumption on the blood plasma levels of oxidatively modified proteins, thiobarbituric acid reactive substances and glucose. However, the contents of thiobarbituric acid reactive substances and products of oxidative modification of proteins were significantly higher in hearts of diabetic rats with chronic alcohol intoxication than in diabetic rats without alcohol intoxication or in rats subjected to chronic alcohol treatment. The alcohol-induced hyperactivation of free radical processes found in the heart may have additional damaging effect.     

Aldosterone and electrolyte content in blood and myocardium of rats after single physical load in acute alcoholic intoxication]

It is shown that acute alcoholic intoxication causes essential changes of aldosterone content and balance of electrolytes in blood plasma of Wistar rat males. The SPL test revealed the inadequate reaction in the mineral-corticoid function of the adrenal glands in the rats with acute alcoholic intoxication. The method of the free choice of the load by the experimental rats is the most optimal way to assess. The rats with acute alcoholic intoxication displayed smaller tolerance to physical load.     

Protective effects of N-acetyl-L-cysteine against acute carbon tetrachloride hepatotoxicity in rats

In recent years, N-acetyl-L-cysteine (NAC) has been widely investigated as a potentially useful protective and antioxidative agent to be applied in many pathological states. The aim of the present work was further evaluation of the mechanisms of the NAC protective effect under carbon tetrachloride-induced acute liver injuries in rats. The rat treatment with CCl4 (4 g/kg, intragastrically) caused pronounced hepatolysis observed as an increase in blood plasma bilirubin levels and hepatic enzyme activities, which agreed with numerous previous observations. The rat intoxication was accompanied by an enhancement of membrane lipid peroxidation (1.4-fold) and protein oxidative damage (protein carbonyl group and mixed protein-glutathione disulphide formations) in the rat liver. The levels of nitric oxide in blood plasma and liver tissue significantly increased (5.3- and 1.5-fold, respectively) as blood plasma triacylglycerols decreased (1.6-fold). The NAC administration to control and intoxicated animals (three times at doses of 150 mg/kg) elevated low-molecular-weight thiols in the liver. The NAC administration under CCl4-induced intoxication prevented oxidative damage of liver cells, decreased membrane lipid peroxidation, protein carbonyls and mixed protein-glutathione disulphides formation, and partially normalized plasma triacylglycerols. At the same time the NAC treatment of intoxicated animals did not produce a marked decrease of the elevated levels of blood plasma ALT and AST activities and bilirubin. The in vitro exposure of human red blood cells to NAC increased the cellular low-molecular-weight thiol levels and retarded tert-butylhydroperoxide-induced cellular thiol depletion and membrane lipid peroxidation as well as effectively inhibited hypochlorous acid-induced erythrocyte lysis. Thus, NAC can replenish non-protein cellular thiols and protect membrane lipids and proteins due to its direct radical-scavenging properties, but it did not attenuate hepatotoxicity in the acute rat CCl4-intoxication model.     

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.     

Post-resuscitation toxemia and possibilities of its correction by albosorb

Albumin with enhanced sorption capacity (albosorb) was infused in animals after 10 min long clinical death caused by blood loss to correct endogenic intoxication. The albosorb infusion enhanced the blood plasma astringency both with respect to hydrophobic and hydrophilic molecules.     

Elevation of Taurine in Hippocampal Extracellular Fluid and Cerebrospinal Fluid of Acutely Hypoosmotic Rats: Contribution by Influx from Blood?

Previous work has demonstrated that there is a selective increase in extracellular taurine in the brain during acute water intoxication. One aim of the present study was to investigate whether plasma taurine contributes to this increase. To this end, the concentrations of taurine, other amino acids, and ethanolamine (EA) were measured in plasma and CSF of urethane-anesthetized rats injected with 150 ml/kg body weight of distilled water. Blood pressure, blood gases, and pH, as well as plasma and CSF osmolality, were also measured. The CSF level of albumin was quantitated to study the function of the blood-CSF barrier. In separate experiments, hippocampal microdialysis was performed to determine the effects of acute plasma hypoosmolality on extracellular amino acids. Finally, the effect of water injection on hippocampal specific gravity and tissue amino acids was assessed. Blood gases and pH were essentially unchanged after water administration. Mean arterial blood pressure increased to peak levels approximately 50 mm Hg above control. Plasma osmolality decreased rapidly, whereas the depression of CSF osmolality was slower and less pronounced. The average volume of the hippocampus increased by 8%. Water injection was accompanied by a 25-fold elevation of taurine in plasma, whereas phosphoethanolamine (PEA) and EA increased moderately. A small fraction of the increase in plasma taurine might derive from blood cells because dilution of blood in vitro led to doubled plasma levels of the amino acid. Taurine, PEA, and EA increased consistently in CSF and hippocampal microdialysates. Plasma hypoosmolality transiently opened the blood-CSF barrier is reflected by augmented CSF concentrations of albumin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in rat mineral metabolism induced by acute ammonium acetate infusion

1. Acute ammonium intoxication in rat was produced by an i.v. overload of 1000 nmoles of ammonium acetate infunded during 15 min. 2. The load of ammonium produced sodium and potassium accumulation in muscle and plasma, minor in liver, and decreased these metal levels in kidney. 3. Blood and muscle magnesium content was strongly altered as a result of ammonium intoxication. 4. Calcium plasma levels, iron blood levels and iron hepatic stock diminished after the ammonium infusion. 5. Copper and zinc homeostasis were insignificantly altered.     

Prostaglandins and cyclic nucleotides in the dynamic development of an experimental poisoning syndrome caused by Yersinia pestis lipopolysaccharide

This work deals with the influence of Y. pestis lipopolysaccharide (LPS), introduced intraperitoneally in a dose of 2 LD50, on the content of prostaglandins (PG), such as PGE, PGF2 alpha and 6-keto-PGF1 alpha, thromboxane, cAMP and cGMP in the liver, lungs and blood plasma of guinea pigs in the process of the development of experimental intoxication. The content of thromboxane in blood plasma increased 2.4-fold in 2 hours after intoxication and remained elevated for as long as 5 hours. Other parameters of blood plasma remained unchanged. The data obtained in this investigation indicate that thromboxane, known as a regulator of thrombogenesis, may induce early disturbances in microcirculation. A change in the content of PG was shown to occur in pulmonary tissue 2 and 5 hours after the beginning of intoxication. The content of PG in liver tissue was found to occur at a later period of the toxic action. The concentration of cyclic nucleotides (CN) in the tissues under study sharply increased even at the initial stage of the development of shock in guinea pigs. The effect of LPS on the metabolism of PG and CN, revealed in this investigation, resembles the effect produced by the thermostable fraction of "mouse" toxin.     

Rat liver mitochondria impairments under acute carbon tetrachloride-induced intoxication. Effects of melatonin

The aim of the present work was to investigate the mechanisms of oxidative damage of rat liver mitochondria in vitro, under hypochlorous acid (HOCl)-induced oxidative stress, and in vivo, under acute carbon tetrachloride-induced intoxication in rats. Hypochlorous acid (50–300 μM), the main inflammatory agent, inhibited liver mitochondria respiratory activity and caused uncoupling in the respiratory and phos-porylation processes. The toxic damage of rat liver after 24 h of acute carbon tetrachloride-induced intoxication (4 g/kg, intragastrically) was accompanied by a significant reduction in succinate- and glutamate-dependent respiration rate in state 3 (by 65%, p < 0.001, and by 50%, p < 0.01, respectively). The respiration control ratio approached 1, reflecting the loss of respiration control. The phosphorylation coefficient significantly decreased due to uncoupling of the oxidation and phosphorylation processes. The mitochondrial alterations were associated with oxidation of intramitochondrial GSH by 25% (p < 0.05), the marked inhibition of succinate dehydrogenase (complex II) by 35% (p < 0.05), and the rise of blood plasma nitric oxide level by 45% (p < 0.05). The impairment of mitochondrial respiratory function may result from the inhibition of enzymatic activities in the respiratory chain and the damage of mitochondrial membrane during intoxication and plays a key role in the development of the CCl₄-induced hepatotoxicity. Melatonin administration under CCl₄-induced intoxication (three times at a dose of 10 mg/kg) increased the rate of succinate oxidation in state 3 by 30% (p < 0.05) and reversed the increase in glutathione peroxidase activity. Melatonin prevented an elevation of nitric oxide level in the blood plasma of intoxicated animals but did not protect mitochondrial functions under acute intoxication.     

Contents of aldosterone and electrolytes in blood plasma and the myocardium of rats after single physical exertion during acute alcoholic intoxication]

It was proved in experiments with male Wistar rats that acute alcohol intoxication caused significant changes in electrolytes balance in blood plasma and myocardium remaining for a long time after ethanol injection. SPL test makes it possible to reveal inadequate reaction of blood plasma aldosterone in alcohol injected rats. This fact may be considered as the fact of involving extracardiac component of compensation of myocardial functional insufficiency conditioned mainly by electrolyte unbalance. The tolerance to physical loading is significantly higher in alcohol injected rats than in intact animals.     

Outbreak of Anticonvulsant Intoxication in an Australian City

An outbreak of anticonvulsant intoxication occurred in epileptic patients in Australia during 1968-9. All affected patients studied in Brisbane were taking one brand of phenytoin. In 87% of them the blood phenytoin levels were above the therapeutic range. Reduction of phenytoin dosage relieved the intoxication in all patients. The excipient in the responsible phenytoin capsules had been changed several months before the outbreak, and this change was probably related causally to the altered blood phenytoin concentrations.     

Effect of the composition of branched chain amino acids, taurine, and tryptophan on the amino acid metabolism in experimental models of alcoholism

Ethanol withdrawal after forced alcoholization of rats according to Majchrowicz led to the development of amino acid imbalance in the pool of free amino acids in the liver (increasing levels of alanine, aspartate, glutamate, glutamine and histidine, decreasing levels of glycine, lysine, threonine and taurine) and blood plasma (increasing levels of tyrosine and alanine, decreasing levels of most glycogen aminoacids, branched-chain aminoacids and Lys). Less profound changes were observed after prolonged alcohol intoxication (decreasing levels of alanine, ornitine, citrulline and increasing level of Glu in liver, increasing levels of sulfur-containing compounds, Asp and Lys in blood plasma). Amino acid mixture which contained branched-chain amino acids, taurine and tryptophan administered intragastrically was found to correct levels of sulfur-containing amino acids, threonine, lysine and isoleucine after ethanol withdrawal and to eliminate disorders in urea cycle, exchange of threonine, glycine and phenylalanine after prolonged alcohol intoxication.     

Leukocytic shifts following pancreatic resection with a plasma scalpel and cryodestruction]

Two series of experiments were carried out on dogs. In the first series, blood leukocytes count was studied after resection of the pancreas using plasma scalpel. The resection caused two-phase leukocyte reaction: neutrocytosis (phase I) and leukocytosis involving mainly lymphocytes and monocytes (phase II). During the first 24 hours after the resection, a sharp increase of the leukocyte intoxication index (LII) was observed. The second series of experiments was performed using the combination of plasma scalpel and cryodestruction. The graphic curves denoted a sharp fall both in total leukocytic counts and in the different types of leukocytes which were plotted separately (neutrophils, eosinophils, etc.) This can be explained by the absence of the second (lympho-monocyte) reaction. Only a slight increase in LII occurred. These results reflect lower degree of the protection and adaptation reactions of leukocytes, this being in favor of a combination of plasma scalpel and cryodestruction during the operation.     

The role of endothelin-1 and nitric oxide in the pathogenesis of hypertension in diabetic patients

The pathogenesis of renal hypertension has not yet been fully clarified. As the potential role of endothelin-1 (ET-1) and nitric oxide (NO) has been postulated, their concentrations were determined in plasma and urine of diabetic patients. The study included 30 diabetic patients (both IDDM and NIDDM) with initial or advanced diabetic nephropathy (decreased endogenous creatinine clearance, proteinuria) and 20 healthy control subjects. The correlation with blood pressure and other renal function parameters was monitored and compared with the control group. Also, the effect of ACE inhibitors (ACEI) on ET-1 and NO patterns was monitored in correlation with arterial hypertension. In diabetic patients that did not receive ACEI therapy, the increase in plasma ET-1 was associated with both systolic and diastolic blood pressure elevation, whereas in those administered ACEI the increase in plasma ET-1 was associated with a systolic blood pressure decline. In addition, the increase in plasma NO was accompanied by a statistically significant decline of both systolic and diastolic blood pressure in diabetic patients receiving ACEI.     

Effect of methanol-induced oxidative stress on the neuroimmune system of experimental rats

It is well known that the nervous system has increased susceptibility to methanol intoxication. The present study reveals the effect of methanol intoxication on antioxidant status, lipid peroxidation and DNA integrity in hypothalamic-pituitary-adrenal (HPA) axis organs and spleen. Non-specific and specific immune functions were analyzed. In addition, open field behavior, plasma corticosterone level and blood methanol level were estimated. Male Wistar albino rats were intoxicated with methanol (2.37 g/kg b.wt., i.p.) for 1 day, 15 and 30 days. Administration of methanol showed significant increase in enzymatic (superoxide dismutase, catalase, glutathione peroxidase), non-enzymatic (reduced glutathione and Vitamin C) antioxidants and lipid peroxidation (LPO) in hypothalamus and adrenal gland of day 1 group. However, decrease in enzymatic and non-enzymatic antioxidants with concomitant increase in LPO level were observed in 15 and 30 days groups. Plasma corticosterone level was significantly increased in day 1 and 15 days groups whereas, 30 days methanol intoxication group showed considerable decrease in corticosterone level compared with control animals. Cell-mediated immune response of footpad thickness was significantly decreased with an increased leukocyte migration inhibition. Humoral immune response of antibody titers was elevated in methanol-intoxicated groups. Neutrophil functions, adherence and phagocytic index (PI) were found to be significantly decreases. Furthermore, significant increase in the avidity index and nitro blue tetrozolium reduction was observed in the methanol exposed animals. Day 1 methanol exposed group showed increased PI compared to the control ones. Methanol exposure for 30 days showed an increased DNA fragmentation in the hypothalamus, adrenal glands, and spleen. In conclusion, exposure to methanol-induced oxidative stress disturbs the HPA-axis function altering the level of corticosterone, which lead to varied non-specific and specific immune response in experimental rats.     

Effect of nitrobenzoic acid on methemoglobin content in blood and activity of antioxidative enzymes in erythrocytes]

Intraperitoneal administration of meta-nitrobenzoic, 3,5-dinitrobenzoic, 2,4,6-trinitrobenzoic and 3,5-dinitro-4-methylbenzoic acids to the white mice in a dose equal to LD50 has induced an increase in the methaemoglobin content in their blood. Total activity of dehydrogenases of pentosephosphate pathway, content of 2,3-diphosphoglycerate increase in response to the intoxication evoked by the mentioned acids. The acute intoxication does not practically change the activity of the key enzymes of antioxidant protection: superoxide-dismutase, catalase and glutathione peroxidase.