Hepatic and renal concentrations of vitamins E and C in lead- and ethanol-exposed rats. An assessment of their involvement in the mechanisms of peroxidative damage.

The study was aimed at investigating vitamin E and vitamin C concentrations in a liver and kidney as well as their involvement in the mechanism of peroxidative action of lead (Pb) and ethanol (EtOH) in these organs in rats receiving 500 mg Pb/l (in drinking water) or/and 5 g EtOH/kg body wt./24h (p.o.) for 12 weeks. The exposure to Pb and EtOH alone and in combination led to a decrease in vitamin E concentration in the liver compared to the control group (by 30%, 26% and 50%, respectively). The decrease in the liver vitamin E concentration in the rats co-exposed to Pb and EtOH was more marked than in those separately treated with these xenobiotics. The treatment with Pb alone and in combination with EtOH led to a decrease in vitamin E concentration in the kidney (by 13% and 21%, respectively). The liver vitamin C concentration decreased as a result of exposure to EtOH, both separately (by 17%) and in combination with Pb (by 11%). The kidney vitamin C concentration increased in the rats exposed to EtOH alone (by 10%), whereas in those treated with Pb, both separately and in combination with EtOH it decreased (by 26% and 6%, respectively). ANOVA/MANOVA analysis revealed that the changes in vitamin E concentration in the liver and kidney at co-exposure to Pb and EtOH resulted from their independent action, whereas those in vitamin C were due to an independent action of these xenobiotics (EtOH in the liver, Pb and EtOH in the kidney) and an interaction between them. There was no correlation between vitamins E and C concentrations in the liver and kidney. The liver concentration of vitamin E and the liver and kidney concentration of vitamin C negatively correlated with malondialdehyde concentration (MDA, lipid peroxidation index) in these organs. Based on the results of the present study and our previous findings in this experimental rat model it can be hypothesized that vitamins E and C are involved in the mechanism of peroxidative action of Pb and EtOH in the liver and kidney, both at separate and combined exposure. The probable protective involvement of vitamins E and C in the damaging action of EtOH and Pb may be related to scavenging of free radicals directly and indirectly generated by these xenobiotics.

Pentobarbital in tobacco.

The spectrometric analysis of extracts from tobacco and tobacco smoke revealed the presence of pentobarbital in the analyzed substances. Tobacco samples and tobacco smoke were extracted with chloroform, determinations were performed with the Perkin-Elmer Autosystem XL system, on a Turbo Mass spectrometer. Subject to analysis were 4 cigarette brands manufactured in Poland and raw, unprocessed tobacco. The presence of pentobarbital in the analyzed samples was confirmed by the analysis of the mass spectrum of the substance, as well as by comparison of retention time with standard of pentobarbital. The determined pentobarbital concentrations in tobacco amounted to 3-6 microg/cigarette, and in tobacco smoke they were approximately 45% lower. In case of tobacco extracts it can with high probability be excluded that pentobarbital is synthesized during chromatographical analysis. The presence of pentobarbital in tobacco is thus beyond question.

Bone mineral density, chemical composition and biomechanical properties of the tibia of female rats exposed to cadmium since weaning up to skeletal maturity.

The influence of exposure to cadmium (Cd) during skeletal development on the risk of bone fractures at the stage of skeletal maturity was investigated on a female rat model of human exposure. The tibias of rats treated with 1, 5 or 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months (since weaning) were used. The exposure to Cd dose- and time-dependently influenced the tibia bone mineral density (BMD) and chemical composition. In skeletally matured animals, at each level of the exposure to Cd, the BMD at the whole tibia and its diaphysis as well as the percentage of minerals content in the bone, including the content of zinc, copper and iron, were decreased compared to control. Moreover, in the 50 mg Cd/l group, the percentage of organic components content increased. The Cd-induced changes, at all levels of exposure, resulted in weakening in the yield strength and fracture strength of the tibia (a three-point bending test of the diaphysis and compression test with vertical loading) of the skeletally matured females. A very important and clinically useful finding of this study is that a decrease (even by several percent) in the tibia BMD results in weakness in the bone biomechanical properties and that the BMD may predict the risk of its fracture at the exposure to Cd. Moreover, the results together with our previous findings seem to suggest that tibia, due to higher vulnerability of its diaphysis, compared to the femoral diaphysis, to damage by Cd may be more useful than femur to investigate the effect of Cd on the cortical bone. The present study revealed that a low exposure to Cd (1 mg Cd/l), corresponding to low human environmental exposure, during the skeletal development affects the tibia mineral status leading to weakening in its mechanical properties at the skeletal maturity. The findings allow for the conclusion that environmental exposure to Cd during childhood and adolescence may enhance the risk of low BMD and fractures at adulthood.

Mechanical properties of femoral diaphysis and femoral neck of female rats chronically exposed to various levels of cadmium.

The effect of chronic exposure to cadmium (Cd) on the mechanical properties of femoral diaphysis and femoral neck was investigated on a rat model of human exposure. Three-week-old female Wistar rats were exposed to Cd in drinking water at concentrations of 1, 5, 50, or 100 mg/L for 12 months. Biomechanical properties of the femoral diaphysis were evaluated in a three-point bending test and those of the femoral neck in a bending test with vertical loading of the head. Bone mineral content (BMC) and bone mineral density (BMD) at the whole femur, and BMD at the diaphysis and proximal femur (head and neck region) of the Cd-treated rats decreased in a dose-dependent manner, except for the diaphyseal BMD at a Cd concentration of 1 mg/L. Exposure to Cd concentrations of 1 and 5 mg/L had only little effect on the diaphyseal mechanical properties (decreased yield load with unchanged bending strength, stiffness, yield stress, ultimate stress, and Young modulus), whereas the bending strength and stiffness of the neck decreased and the yield load clearly tended to decline or declined. The effect of Cd at the two locations was more marked in the 50 and 100 mg/L groups, and changes in the bone geometry were observed in these animals. The results clearly revealed that chronic, even low-level, exposure to Cd results in demineralization and weakening of the femur. The femoral neck seems to be more vulnerable than the diaphysis to failure from Cd. We conclude that environmental exposure to Cd may be an important risk factor for femoral neck fracture.

Low-level lifetime exposure to cadmium decreases skeletal mineralization and enhances bone loss in aged rats.

The effects of low-level lifetime exposure to cadmium (Cd) on the skeleton mineral status and the risk of bone loss in the elderly were studied in an experimental model of human environmental exposure in non-Cd-polluted areas. Young female Wistar rats were exposed to 1 mg Cd/l in drinking water for 24 months. Bone mineral content (BMC), density (BMD) and area of the lumbar spine (L1-L5) and femur, and total skeleton BMD (T-BMD) were measured densitometrically at the baseline and after 6, 12, 18, and 24 months. Prevalence of osteopenia and osteoporosis was evaluated based on the BMD T score and Z score. Osteocalcin (OC) in the serum and total alkaline phosphatase (total ALP) in the serum, cortical and trabecular bone samples as bone formation markers, and C-terminal cross-linking telopeptide of type I collagen (CTX) in the serum and urine as bone resorption markers were measured. Calcium (Ca) and Cd concentrations in the serum/blood and urine were determined as well. In the Cd-exposed females, the L1-L5 and femur BMC and BMD at all the studied time points were lower compared to control. The exposure to Cd resulted in lower accumulation of peak bone mass, accelerated osteopenia, and enhanced the prevalence of osteoporosis in aged rats. The effect of Cd was more pronounced at the L1-L5 than at the femur. CTX concentration in the urine was decreased after 6 months and next increased compared to control, whereas the urinary loss of Ca was enhanced during the exposure to Cd. After 24 months of the treatment, the serum total ALP activity and the activity of this enzyme in cortical and trabecular bone decreased and serum CTX concentration increased, whereas the concentrations of OC and Ca were unchanged. The study clearly revealed that low-level lifetime exposure to Cd diminishes the accumulation of bone mass during skeletal growth and influences bone metabolism at maturity causing osteopenia, and enhances the age-related bone loss due to high turnover rate leading in consequence to osteoporosis in aged rats. The results together with our previous findings confirm the hypothesis that environmental exposure to Cd may be a risk factor for skeletal diseases.

Mineral status and mechanical properties of lumbar spine of female rats chronically exposed to various levels of cadmium.

The effects of chronic exposure to cadmium (Cd) on the mineral status, mechanical properties and incidence of deformities and fractures of the lumbar spine (L1-L5) were studied in a rat model of human exposure. Young female Wistar rats were exposed to 1, 5, 50 or 100 mg Cd/l for 12 months. Cd, dose and time dependently, disturbed the mineral status of the lumbar vertebrae as reflected in decreased bone mineral content (BMC) and density (BMD) at the L1-L5 (DEXA technique) and ash weight (AW) of the fourth lumbar vertebral body (L4). However, the changes were too small to be evident radiographically. Cd had no effect on the ratio of nonorganic to organic component content, except for its decrease at the 100 mg Cd/l. Weakness in the mechanical properties (compression test; Instron machine) of the L4 was noted. At the 1 mg Cd/l, a decrease was observed in the deformation at the yield point, with a simultaneous increase in the L4 stiffness, but not in strength (defined by load at yield or ultimate load). In the 5 mg Cd/l group, similar changes took place and a decrease in the ultimate load was evident as well. At the 50 and 100 mg Cd/l, Cd more seriously affected the L4 mechanical properties. At all levels of Cd exposure, the L4 deformities and/or fractures took place. Intact L4 was noted only in the 1 and 5 mg Cd/l groups. The study clearly revealed that chronic exposure to Cd disturbs the L1-L5 mineral status resulting in weakness in its mechanical properties and in turn in vertebral body (cancellous bone) deformities and fractures. The results allow us to conclude that the critical Cd concentration for these effects is very low [about 0.06-0.09 microg/g dry defatted weight (DW)] and seem to indicate an osteoporotic character of changes. A very important finding of the study is that Cd affects cancellous bone even at low-level intoxication corresponding to the general population exposure. Thus, we hypothesize that environmental exposure to Cd may be a risk factor for the lumbar spine demineralization and increased incidence of vertebral deformities and fractures.

Antioxidant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol.

The oxidative status of liver and kidney of rats co-exposed to cadmium (50 mg Cd/l in drinking water) and ethanol (5 g EtOH/kg body weight/24 h, intragastrically) for 12 weeks was studied. The activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) as well as the concentration of malondialdehyde (MDA), as an indicator of lipid peroxidation, were measured in homogenates of the liver and kidney. Concentrations of zinc (Zn), copper (Cu), iron (Fe) and Cd in the serum or blood, and their content in the liver and kidney as well as EtOH concentration in the whole blood were assayed. Daily Cd intake in the Cd and Cd+EtOH groups was similar and ranged from 2.39 to 4.88 mg/kg body weight/24 h and from 2.64 to 4.14 mg/kg body weight/24 h, respectively. After the administration of EtOH alone, the activity of SOD increased in the kidney and decreased in the liver, whereas the activity of CAT decreased in both these organs, and MDA concentration increased in the liver and was unchanged in the kidney. The exposure to 50 mg Cd/l led to a decrease in the activities of SOD in the liver and CAT in the liver and kidney, and an increase in the kidney activity of SOD and MDA concentration in both these organs. In the rats co-exposed to Cd and EtOH, the kidney activity of SOD and the liver concentration of MDA were lower, whereas the kidney activity of CAT was higher compared to the Cd group. The concentration of Fe in the serum and its content in the liver of rats treated with EtOH increased, whereas the concentrations of Zn and Cu in the serum and the content of Zn, Cu and Fe in the kidney and that of Zn and Cu in the liver were unchanged. In the liver and kidney of rats treated with Cd alone, the content of Fe was decreased and that of Zn and Cu was enhanced. After EtOH administration to Cd-exposed rats, a decrease in Cu serum concentration and its liver content and an increase in Fe concentration in the serum and its content in the liver and kidney, compared to the group exposed to Cd alone, were noted. Moreover, EtOH decreased the blood Cd concentration and its accumulation in the liver and kidney of these animals. EtOH alone decreased Cd content in the liver and increased in the kidney, however the whole content of Cd in these organs was unchanged compared with control. The results of this study indicate that despite the ability of Cd and EtOH to induce the oxidative stress the effect in the liver and kidney is not intensified at simultaneous exposure to both substances. The changes in the studied indicators of oxidative stress (SOD, CAT and MDA) observed in the kidney and especially in the liver of the rats co-exposed to Cd and EtOH may result from an independent effect of Cd and/or EtOH and also from their interaction. The interactive effect may involve, among others, changes in Cd accumulation and content of Zn, Cu and Fe in these organs and their concentration in serum. Since the rats treated with Cd and Cd+EtOH had reduced drinking fluids intake that might result in dehydratation, the effect of the both xenobiotics on the oxidative status of the body may be not solely due to Cd and/or EtOH, but also the modyfing influence of accompanying alterations such as reduced water intake and dehydratation. The results of the study allow us to hypothesize that Cd-exposed alcohol misusers are not at enhanced risk of liver and kidney damage due to lipid peroxidation.

A preliminary study of the submandibular gland of the rat after one-year cadmium intoxication. Part I. Cadmium concentration.

The aim of the present study was to establish to what degree a one-year exposure of rat females to 5, 50 and 100 mg Cd/l affects the weight of the submandibular glands and their cadmium levels. We observed a decrease in the weight of the submandibular glands in the rat females from Groups I, II and III, compared to the control rats. We also found an increase in cadmium levels in the submandibular glands in Groups I, II and III, in comparison to the control. The highest cadmium concentration was noted in the submandibular glands in Group III, which was accompanied by the greatest weight reduction, the correlation being negative. The present experiment indicates that one-year administration of cadmium to rat females at a dose of 5, 50 and 100 mg Cd/l leads to a cadmium dose-dependent decrease in the weight of the submandibular glands.

Iron body status of rats chronically exposed to cadmium and ethanol.

AIMS: The present study was performed to assess the effect of simultaneous long-term exposure to cadmium (Cd) and ethanol on iron (Fe) status of male Wistar rats. METHODS: The animals received drinking water containing 50 mg of Cd/l and/or 10% (w/v) ethanol for 12 weeks. Fe and Cd concentrations in serum (blood), certain tissues, urine and feces were determined by atomic absorption spectrometry. The total pool of Fe was calculated as a sum of its content in liver, spleen, kidneys, heart and brain. Fe bioavailability was evaluated based on its apparent absorption. RESULTS: The daily Cd intake ranged from 3.17 to 4.28 mg/kg (Cd group) and from 2.41 to 3.17 mg/kg (Cd + ethanol group); ethanol consumption ranged from 47.5 to 86.9 g/kg/24 h (ethanol group) and from 47.3 to 63.4 g/kg/24 h (Cd + ethanol group). Exposure to Cd or/and ethanol caused serious disturbances in Fe metabolism, as indicated by Fe body depletion. Both substances, applied alone and in combination, reduced the apparent Fe absorption and decreased its total pool in certain organs, and urinary excretion. However, the Cd- and ethanol-induced changes in the tissue Fe concentrations were different. Cd exposure decreased the concentration of Fe in serum, liver, spleen and femur, whereas ethanol decreased it in the spleen. In rats co-exposed to Cd and ethanol, decreased serum, spleen and brain Fe concentrations were all observed. CONCLUSIONS: The changes in Fe status in rats co-exposed to Cd and ethanol can be explained by the independent action of the two substances, leading to a decrease in Fe bioavailability, or by their interactions, which involves a modifying effect of ethanol on Cd turnover. The results allow the conclusion that ethanol may increase Cd accumulation, making the organism more susceptible to Fe depletion. Alcoholics thus may be at increased risk of disorders in Fe body status.

Liver and kidney function and histology in rats exposed to cadmium and ethanol.

AIMS: The present study was performed to assess the function and histology of the liver and kidney in rats exposed to 50 mg Cd/l (as cadmium chloride) and/or 10% (w/v) ethanol (EtOH) for 12 weeks. METHODS: The activities of alanine aminotransferase (ALAT) and asparate aminotransferase (AspAT) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, total protein and urea concentrations in serum and urine, as well as urinary alkaline phosphatase (ALP) activity were determined, and creatinine clearance was calculated. Both organs were subjected to histopathological analysis. RESULTS: Daily Cd intake ranged from 3.17 to 4.28 mg/kg body weight and from 2.41 to 3.17 mg/kg body weight in the Cd and Cd + EtOH groups, respectively. The daily intake of 10% EtOH ranged from 47.5 to 86.9 g/kg body weight in the EtOH and from 47.3 to 63.4 g/kg body weight in the Cd + EtOH-exposed rats. Cd and EtOH, independently of separate or combined application, changed liver and kidney function and histology. Rats treated with Cd alone and those co-exposed to both substances showed qualitatively similar, but different magnitudes of changes, in liver and kidney histology. Blurred trabecular structure, vacuolar degeneration and increased density of nuclear chromatin with very compact nuclear structure were found in hepatocytes of zones 2 and 3. Moreover, mononuclear cell infiltrations and necrosis of single cells were evident in zone 1. In the kidney tubules, degeneration and hypertrophy of epithelial cells and dilation in the glomeruli were also observed. Some functional (increased serum AspAT and urinary ALP, decreased urinary urea) and structural changes in the liver and kidney were more evident in the case of combined exposure, while others were more evident after single exposure. However, a decrease in creatinine clearance, noted only in the animals treated with Cd and EtOH, shows that functional changes indicating renal insufficiency are more serious in the co-exposed group. CONCLUSIONS: Due to lower Cd and EtOH intake (resulting from a stronger aversion to drinking water containing both substances) in the co-exposed rats, as compared to the Cd- and EtOH-treated groups, it is difficult to draw a definite conclusion from this study. The findings, however, seem to indicate that EtOH increases Cd nephrotoxicity in rats, and thus may suggest a higher risk of kidney damage in alcoholics exposed to Cd. Unfortunately, this study does not provide clear evidence if, and to what extent, EtOH influences Cd hepatotoxicity.

Effect of chronic administration of cadmium on the rat thyroid: radioimmunological and immunohistochemical studies.

The effect of chronic (12 months) oral cadmium (Cd) administration (5 or 50 mg Cd/dm3) to rats on the structure and function of the thyroid was evaluated. Paraffin thyroid and parathyroid sections were stained with H+E and immunocytochemically for calcitonin (CT), somatostatin (ST), synaptophysin (SPh), chromogranin A (CgA) and thyroid transcription factor-1 (TTF-1). Serum levels of thyroid hormones: triiodothyronine (T3) and tetraiodothyronine (T4) as well as levels of Cd in the blood and calcium (Ca) in the serum were estimated. CT, ST and SPh were detected in C cells of the thyroid, while CgA in both thyroid and parathyroid cells. In animals exposed to Cd, proliferation of CT- and SPh-positive thyroid C cells was observed, ST being found only in very few C cells--both in control animals and in those exposed to Cd. Serum T3 concentration was not affected by Cd, while T4 was reduced but only at the exposure to the higher Cd concentration. Moreover, the rats exposed to Cd showed a decrease in serum Ca concentration.

Cadmium turnover and changes of zinc and copper body status of rats continuously exposed to cadmium and ethanol.

The effects of continuous exposure to cadmium (Cd) and ethanol on Cd turnover and zinc (Zn) and copper (Cu) body status of male Wistar rats were studied. The animals received an aqueous solution of 10% (w/v) ethanol and/or 50 mg Cd/l as the only drinking fluid for 12 weeks. The concentrations of Zn, Cu and Cd in the serum (or blood), liver, kidneys, spleen, brain, heart, femoral muscle and femur as well as in 24-h urine and faeces specimens were assessed by atomic absorption spectrometry (AAS). Ethanol alone had no effect on Cd accumulation or excretion. By contrast, co-administration of ethanol with Cd influenced the turnover of this toxic metal. Long-term consumption of ethanol alone caused a decrease in femur Zn and liver Cu concentrations. Moreover, the urinary loss of both bioelements decreased, whereas their faecal excretion was increased. Exposure to Cd resulted in an increase in liver and kidney and in a decrease in femur and 24-h urine Zn concentrations. An increase in Cu concentration in the kidney and a decrease in the brain were also noted. Moreover, Cd increased the total pool of Zn in organs (kidneys, liver, spleen, heart and brain), but did not influence that of Cu. Zn concentration in the liver, kidney and spleen of rats co-exposed to Cd and ethanol were increased, but were decreased in the brain and femur, compared to controls. The concentrations of Cu in livers and brains of these rats were decreased, whereas those in kidney, spleen and heart were increased. The urinary excretion of the elements was decreased, whereas their faecal excretion was increased. Moreover, the total amount of Cu in organs decreased below the control value and that of Zn was in the normal range. These changes in Zn and Cu levels could be explained by different effects of both toxic substances, differences in bioelement intakes (due to reduced consumption of drinking solutions and food), and the modifying effect of ethanol on Cd turnover. Our results suggest that alcoholics may be more susceptible to Cd accumulation and its effects on body Zn and Cu.

Interactions between cadmium and zinc in the organism.

It is well known that many toxic effects of cadmium (Cd) action result from interactions with essential elements, including zinc (Zn). These interactions can take place at different stages of absorption, distribution in the organism and excretion of both metals and at the stage of Zn biological functions. Exposure to Cd leads to disturbance in Zn in the organism on the one hand, while dietary Zn intake has an important effect on Cd absorption, accumulation and toxicity on the other. The Zn status of the body is important in relation to development of Cd toxicity. Numerous data show that increased Zn supply may reduce Cd absorption and accumulation and prevent or reduce the adverse actions of Cd, whereas Zn deficiency can intensify Cd accumulation and toxicity. In this review, the interactions between these two trace elements in humans and animals are discussed on the basis of the available literature and our own results, against the background of general population exposure to Cd and common nutritional deficiency of Zn.

The effect of zinc supply on cadmium-induced changes in the tibia of rats.

It has been determined that zinc supplementation (240 microg Zn/ml) during (for 12 weeks) or after (for 2 weeks) cadmium exposure (50 microg Cd/ml for 12 weeks) can prevent the accumulation and toxic action of Cd in the tibia of rats. The exposure to Cd led to disturbances in bone metabolism reflected by changes in the chemical composition of bone and decreased bone mineral density (osteomalacian changes). The Zn supply in conditions of Cd intoxication completely prevented the Cd-induced increase in percentage of water content and decrease in tibia ash weight, ash weight/dry weight, non-org. comp./org. comp., Zn content and concentration. Moreover, Zn partly protected from the decrease in Ca concentration and content, percentage of non-organic components content, Ca/wet weight, Ca/ash weight and Ca/dry weight. Zn administered after Cd exposure partly, but not completely, protected from Cd-induced decrease in percentage of non-organic components content, Ca/wet weight as well as Ca content and concentration. This protective effect on bone was most evident when Zn was administered during Cd exposure. But Zn, independently of the manner of its administration, did not prevent Cd accumulation in the tibia. Our results suggest that Zn supply in conditions of simultaneous exposure can prevent Cd-induced bone loss to some extent, and used after Cd treatment can give therapeutic benefits.

Effect of short-term ethanol administration on cadmium retention and bioelement metabolism in rats continuously exposed to cadmium.

The present study was performed to assess the effect of short-term ethanol administration on cadmium retention and accumulation as well as on bioelement metabolism (zinc, copper, calcium, and magnesium) in rats exposed to an aqueous solution of cadmium chloride for 8 weeks. Intoxication with cadmium led to accumulation of this toxic metal, particularly in the liver and kidney, which was linked to metallothionein synthesis as well as to a disturbance in the metabolism of zinc, copper, and calcium. These effects were dependent on the level of exposure. The administration of ethanol in the final phase of cadmium treatment increased cadmium retention and accumulation in the body with simultaneous elevation in liver and kidney metallothionein concentration. Ethanol alone or with cadmium caused or intensified the cadmium-induced changes in metabolism of zinc and copper. Calcium metabolism disturbed by cadmium was not influenced by ethanol. Neither agents had any effect on magnesium metabolism. We conclude that even short-term ethanol consumption in conditions of exposure to cadmium can increase this heavy metal body burden and lead to more serious disturbances in metabolism of important elements such as zinc and copper. Cadmium- and ethanol-induced changes in the homeostasis of these microelements are probably connected with the ability of both xenobiotics to cause metallothionein induction.

Evaluation of the influence of N-nitrosodimethyloamine (NDMA) on the apoptosis of neutrophils of peripheral blood (PMN) and the expression of the IL-6R membrane receptor--in vitro research.

Evaluation of the influence of N-nitrosodimethyloamine (NDMA) on the apoptosis of neutrophils of peripheral blood (PMN) and the expression of the IL-6R membrane receptor - in vitro research. The aim of the present work was the evaluation of N-nitrosodimethyloamine (NDMA) on the induction of apoptosis in the neutrophils of peripheral blood as well as the evaluation of the surface receptors for IL-6. The isolated neutrophils were incubated for 1 and 3 hours with NDMA of a concentration of 2.5, 5, 7.5, and 10 mg/ml. In the samples incubated for 1 hour a significant, dose- dependent increase of apoptosis in the examined cells was observed. In the cells incubated for 3 hours, the increase of apoptosis was observed only at concentration of NDMA of 2.5 and 5 mg/ml. In case of higher concentration used, probably necrotic processes dominated in the cells. No influence of NDMA on the expression of IL-6R was observed.

[The impact of acute poisoning by chlorfenvinphos on the activity of antioxidant enzymes and concentration of malondialdehyde in rats]. / Wplyw zatrucia ostrego chlorfenwinfosem na aktywnosc enzymów antyoksydacyjnych oraz stezenie dialdehydu malonowego u szczurów.

The aim of this paper was examination of the influence of chlorfenvinphos on the activity of an antioxidant enzymes in the blood and concentration of the serum malonondialdehyd in rats. It were found increase of the activity of SOD in 24 h and decrease in the 48 h; increase CAT activity, decrease GR activity in the 48 h and increase of G-6-P-DH activity in the 24 and 48 h after intoxication. Activity of GPX did not change statistically significant. It was observed decrease of MDA concentration in the serum in 1 and 24 h after intoxication and return to value in the control groups in the 48 h. It can be concluded that the changes of the activity of enzymes and concentration of MDA in the blood indicates hypoxia in the first period of intoxication (to 24 h) and reoxidation process in the later period.

The influence of calcium content in diet on cumulation and toxicity of cadmium in the organism.

Voluminous literature data show that great interdependence exists between the nutrition status of the organism and the degree of accumulation and toxicity of heavy metals. In this work, the connection between dietary calcium and cadmium toxicity is discussed from the toxicological point of view. Cadmium is one of the most dangerous occupational and environmental poisons. The intake of diet containing an inappropriate amount of calcium causes increased absorption of cadmium from the gastrointestinal tract and increased accumulation of this metal in the organism, finally leading to enhancement of cadmium toxic action. The large intake of calcium protects against absorption, cumulation and toxicity of this heavy metal. Interactions between calcium and cadmium may take place at different stages of their metabolism (absorption, distribution in the organism, elimination) and cadmium may interfere with the biological functions of Ca2+ ions.

[Changes in rats liver in late period of intoxication with chlorphenvinphos in a single dose]. / Zmiany w watrobie szczura w póznym okresie zatrucia chlorfenwinfosem w dawce jednorazowej.

The present investigation was undertaken to study the effect of chlorphenvinphos on the activity of liver enzymes in acute poisoning with this compound. The investigation was carried out on male Wistar rats. The animals received oil--control group and oil solution of chlorphenvinphos in dose 0.5 or 0.1 LD50--the examined group, intragastrically. Material for examination was collected in the 48 h after intoxication. Activity of GOT and GPT in a serum, cytosolic and mitochondrial fractions of liver; BGR and AcP in a serum and lysosomal fraction of liver, ChE in a serum and concentration of lactate in the cytosolic fraction of liver were assayed. It can be concluded that in the 48 h after intoxication with chlorphenvinphos, activity of ChE was normalized in the case of lower dose and has such tendency in the case of higher dose. The changes of other assayed parameters in the serum and liver homogenate indicates that in this period of study, the liver is in point of no return.