Erzsébet Tátrai

Acute effects of cadmium on preovulatory serum FSH, LH, and prolactin levels and on ovulation and ovarian hormone secretion in estrous rats

On the day of diestrus II CFY rats were given 5, 10, or 15 mg/kg cadmium chloride (CdCl2) or 1.0 mL/kg of 0.9% NaCl. On the next day a group of animals was anesthetized with pentobarbital and blood was collected from the aorta at 13:00, 15:00, 16:30, or 18:00 h. for FSH, LH, prolactin (PRL), progesterone (P), and estradiol-17 beta (E2) determination. On the day of the expected estrus, the second group of animals was anesthetized with pentobarbital and cannulas were inserted in one of the femoral arteries and veins, and in one of the utero-ovarian veins. Five-minute blood fractions were collected from the ovary for 40 min, and following the first blood samples, 10 IU hCG was injected iv. Ovarian venous outflow and blood pressure were continuously recorded. From the blood fractions, P and E2 were determined, and their secretion rates were calculated. In a third group of treated animals, the ovaries were excised for histological examination, and oviducts were flushed for counting oocytes. CdCl2 in the dose of 10 or 15 mg/kg increased the PRL serum levels at 13:00 h; it diminished FSH serum levels in the dose of 10 mg/kg and LH serum levels in the doses of 10 and 15 mg/kg at 15:00 h. The decrease in LH levels continued until 16:30 h in the dose of 10 mg/kg CdCl2. In estrous animals, CdCl2 did not influence the blood pressure and ovarian blood flow. In animals receiving 10 or 15 mg/kg CdCl2, a decrease in basal secretion of P occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential toxic effects of iron oxide nanoparticles in in vivo and in vitro experiments

The aim of this study was to determine the potential toxic effects of iron(II,III)oxide nanoparticles (IONPs). In in vivo experiments, the toxic effects of IONPs were monitored in adult male Wistar rats by morphological methods after a single intratracheal instillation. For the control group 1 ml of physiological saline per animal was given, and the treatment group received the same volume of a suspension containing 1 and 5 mg kg−1 body weight IONPs. Lungs and internal organs underwent histopathological examination after 1, 3, 7, 14 and 30 days. The mutagenic effect of these nanoparticles was evaluated by the bacterial reverse mutation assay on Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains, and on Escherichia coli WP2uvrA strain, in the presence and absence of the mammalian metabolic activation system S9. The in vitro cytotoxic effect of IONPs was also examined in Vero cells after short‐term (4 h) and long‐term (24 h) exposure. There were no pathological changes in examined internal organs, except a very weak pulmonary fibrosis developing by the end of the first month in the treated rats. While in vitro MTT assay showed a moderate cytotoxic effect, IONPs proved to be devoid of mutagenic effect in the bacterial systems tested. The results may be a useful extension of our knowledge on the safety of magnetite nanoparticles in view of their possible medical applications, such as in hyperthermia and magnetic resonance imaging. Copyright

Studies on the embryotoxic effects of ortho-, meta- and para-xylene

Abstract CFY rats were exposed to inhalation of ortho -, meta -, or para -xylene at 150, 1500, or 3000 mg/m 3 concentration for 24 h/day from day 7 to day 14 of pregnancy. Additional groups of 3 rats were exposed to o -xylene at 150, 1500, or 3000 mg/m 3 concentrations for 2 h only on the 18th day of pregnancy. In this latter group of rats exposed to o -xylene 18th day of pregnancy, the o -xylene concentration in the blood of the rats was proportional to that in the atmosphere. The solvent crossed the placenta; it was present in the fetal blood and amniotic fluid. All the 3 xylene isomers inhaled at the highest concentration brought about toxic effects in the mother animals. All the 3 isomers brought about the retardation of fetal development: a decrease in the weight of the fetuses, an increase in the incidence of the symptoms of skeletal retardation, a decrease in the activity of different enzymes, succinic dehydrogenase, alkaline- and acid phosphatase and glucose 6-phosphatase, characteristic features of the functional maturity of the nephron. Retardation of the fetuses was dose-dependent, but also dependent on the chemical structure of the particular isomer; their effectiveness was para -, ortho - and meta -xylene in the decreasing order of potency. None of the isomers proved to be teratogenic. Meta - and para -xylene inhalation at the highest concentration increased the incidence of extra ribs. Preimplantation fetal loss was increased by meta - and para -xylene, meta -xylene at the highest concentration interfered with the process of implantation, while para -xylene exposure resulted in an increased postimplantation loss of the fetuses. Ortho -xylene inhalation was without effect on the incidence of the extra ribs, either on implantation, or on the pre- and postimplantation fetal losses.

Effects of cobalt sulfate on prenatal development of mice, rats, and rabbits, and on early postnatal development of rats

The effects of cobalt sulfate administered to pregnant C57Bl mice, OFA-SD rats, and New Zealand rabbits was studied on fetal and postnatal offspring. Cobalt concentration in the maternal blood was increased in proportion to the administered doses. Cobalt crossed the placenta and appeared in the fetal blood and amniotic fluid. Regardless of the administered dose of cobalt sulfate, cobalt concentration in the blood peaked 2 h after administration. Cobalt produced dose-dependent maternal toxicity and was found to be embryotoxic in all three species, as evidenced by elevated frequency of fetuses with body weight or skeletal retardation and embryolethality. Cobalt increased the frequency of major anomalies significantly in mice and rats, with anomalies of the eyes, kidneys, skull, spine, and sternum in mice, and anomalies of the urogenital system in rats. Cobalt sulfate was not teratogenic in rabbits. Intra-amnial administration of cobalt sulfate produced a dose-dependent increase of the frequency of dead fetuses, and weight retardation of the live fetuses. The direct cytotoxic effect probably plays a role in the embryotoxic and teratogenic effects of cobalt. The postnatal examinations revealed a decrease of the perinatal index in the treated group. The body weight of the pups in the treated group was lower during wk 1 of life, but no difference was found between the control and treated by the end of wk 2. Eye opening was completed in the usual time period in both groups, while time of appearance of the teeth, descending of the testes, shaping of ears, and development of hearing was delayed in the treated group. The development of muscle strength and of the locomotor system was delayed. All the functions studied (forward movement, swimming, righting reflex) normalized by postnatal d 21, with the exception of muscle strength. It was concluded that cobalt sulfate exposure decreases the perinatal viability of the fetuses, but the functions of the surviving fetuses with perinatal retardation become compensated by postnatal wk 2-3. The development of fetuses is undisturbed thereafter.

Study on the role of maternal sex steroid production and metabolism in the embryotoxicity of para-xylene☆

CFY rats were exposed to inhalation of clean air or air containing para-xylene (3000 mg/m3) on the 10th, and 9th and 10th days of gestation. Uterine and ovarian venous blood flow, fetal weight, ovarian progesterone and 17 beta-oestradiol secretion, and the progesterone and 17 beta-oestradiol level of peripheral blood (uterine and femoral veins) were measured on the 11th day of gestation. Exposure to para-xylene decreased the weight of the fetuses and the progesterone and 17 beta-oestradiol levels of peripheral blood, but it did not influence the uterine and ovarian venous outflow and the ovarian progesterone and 17 beta-oestradiol secretion rate. It is concluded that para-xylene, by inducing the hepatic monooxygenase system, facilitates the biotransformation of progesterone and 17 beta-oestradiol, which is metabolized by this enzyme system. The decrease in the sex hormone level of peripheral blood is supposed to play a role in the embryotoxicity (retarding and lethal effects) of para-xylene.

In vivo pulmonary toxicity of cellulose in rats.

Cellulose after a single intratracheal dose (15 mg per animal) brought about fibrosing granulomatous alveobronchiolitis and an increase of IgA production in the bronchoalveolar lavage. Fibrosing alveolitis showed moderate progression as a function of time. With different morphological methods, injury of type I pneumocytes and the incomplete repair of type II pneumocytes were detected. The damage of the alveolar epithelium initiated and activated a series of processes that led to definite pulmonary alterations: pulmonary fibrosis leading to the disintegration of the alveolo‐capillary morphological functional unit.

Embryotoxic and teratogenic effects of indium chloride in rats and rabbits.

Daily indium chloride doses of control (0), 50, 100, 200, or 400 mg/kg were administered orally to Sprague-Dawley rats by gavage, on d 6-15 of gestation, and daily metal doses of control (0), 50, 100, or 200 mg/kg were administered to New Zealand rabbits on d 6-20 of gestation. Further groups of pregnant rats were treated with control (0) or 400 mg/kg indium chloride orally on one of d 8, 9, 10, 11, 12, 13, 14, or 15 of gestation. The dams and fetuses were examined on d 21 (rats) and 30 (rabbits) of gestation, using standard teratological methods. Indium concentration was determined in the maternal and fetal blood, as well as in the amniotic fluid, by atomic absorption spectrometry. Indium was found to cross the placenta and appeared in fetal blood in proportion to the metal concentration of the maternal blood. In the amniotic fluid, indium concentrations remained below the detection limit. In rats, indium chloride produced dose-dependent maternal toxic effects, with a dose of 400 mg/kg inducing embryotoxicity (embryolethality) and teratogenicity. Doses of 200 and 100 mg/kg were embryotoxic (retarding) and teratogenic, causing skeletal and visceral anomalies in addition to external anomalies (rudimentary or missing tail, syndactylia, clubfoot, exencephalia) in rats. In rabbits, 200 mg/kg indium chloride was lethal for the dams and the embryos (some of the animals died, and the number of abortions and full resorptions increased). This dose was found to be teratogenic (caused gross renal anomalies) and increased the frequency of fetuses with skeletal retardation. In rats, the effects of indium chloride causing fetal retardation was found to be independent of exposure time. The teratogenic effects were the highest on d 11 and 12 of gestation, when indium chloride caused gross external malformations. Data suggest that the teratogenic effects of indium chloride can be attributed primarily to a direct cytotoxic action of indium resulting from placental transfer, but the effect is not a selective one, as it appears only in the presence of maternal toxic effects.Daily indium chloride doses of control (0), 50, 100, 200, or 400 mg/kg were administered orally to Sprague-Dawley rats by gavage, on d 6-15 of gestation, and daily metal doses of control (0), 50, 100, or 200 mg/kg were administered to New Zealand rabbits on d 6-20 of gestation. Further groups of pregnant rats were treated with control (0) or 400 mg/kg indium chloride orally on one of d 8, 9, 10, 11, 12, 13, 14, or 15 of gestation. The dams and fetuses were examined on d 21 (rats) and 30 (rabbits) of gestation, using standard teratological methods. Indium concentration was determined in the maternal and fetal blood, as well as in the amniotic fluid, by atomic absorption spectrometry. Indium was found to cross the placenta and appeared in fetal blood in proportion to the metal concentration of the maternal blood. In the amniotic fluid, indium concentrations remained below the detection limit. In rats, indium chloride produced dose-dependent maternal toxic effects, with a dose of 400 mg/kg inducing embryotoxicity (embryolethality) and teratogenicity. Doses of 200 and 100 mg/kg were embryotoxic (retarding) and teratogenic, causing skeletal and visceral anomalies in addition to external anomalies (rudimentary or missing tail, syndactylia, clubfoot, exencephalia) in rats. In rabbits, 200 mg/kg indium chloride was lethal for the dams and the embryos (some of the animals died, and the number of abortions and full resorptions increased). This dose was found to be teratogenic (caused gross renal anomalies) and increased the frequency of fetuses with skeletal retardation. In rats, the effects of indium chloride causing fetal retardation was found to be independent of exposure time. The teratogenic effects were the highest on d 11 and 12 of gestation, when indium chloride caused gross external malformations. Data suggest that the teratogenic effects of indium chloride can be attributed primarily to a direct cytotoxic action of indium resulting from placental transfer, but the effect is not a selective one, as it appears only in the presence of maternal toxic effects.

In vitro and in vivo assessment of the pulmonary toxicity of cellulose

The lung‐damaging effect of intratracheally administered cellulose was studied by biochemical and histological methods. Cell count, protein, phospholipid, lactate dehydrogenase and acid phosphatase were determined in bronchoalveolar lavage fluid 1, 3 and 7 days after intratracheal instillation. Histological tests were performed after days 1, 3 and 30. In vitro, cellulose did not damage the macrophage cells. In vivo, interstitial oedema as well as the initial signs of inflammation could be detected in the lung after the first day. Inflammation after 1 week could be noted, partly interstitial and partly intra‐alveolar and intrabronchial. In the bronchoalveolar lavage fluid, protein, lactate dehydrogenase, acid phosphatase, phospholipid and cell count were enhanced after days 1 and 3. After 1 month, the developing bronchioalveolitis is fibrous in character. Contrary to the in vivo study, cellulose did not damage rat peritoneal macrophages.

Effect of toluene exposure on the liver under different experimental conditions.

Abstract The effect of exposure to toluene inhalation was studied in adult mice, rats, and rabbits, and, further, in rats of different age groups and rats subjected to partial hepatectomy or ligation of the common bile duct. It was found that (1) toluene has no substantial liver damaging effect on the mouse, rat, or rabbit; (2) induction of microsomal monooxygenase enzymes by toluene is almost completely independent of physiological changes affecting the functional-anatomical state of the liver (aging), of restriction of the functional capacity of the organ (partial hepatectomy), and of irreversible hepatic damage (bile duct ligation); (3) toluene does not in any way interfere with surgically induced hepatic damage. The consequences of surgical interventions, in turn, just like the age-dependent changes, do not modify the minimal ultrastructural damaging effect of toluene.

Characterisation of lectin binding patterns of mouse bronchiolar and rat alveolar epithelial cells in culture.

Lung epithelial cell differentiation pathways remain unclear. This is due in part to the plasticity of these cells and the lack of markers which accurately reflect their differentiation status. The aim of this study was to determine if lectin binding properties are useful determinants of functional differentiation status in vitro. Mouse Clara cells were cultured for 5 days. During this time, no alteration in differentiation was evident by electron microscopy. No significant alteration in binding reactivity of Bauhinia purpurea (BPA), Maclura pomifera (MPA), Concanavalin A, Wheat germ or Helix pomatia lectins occurred in cultures compared with Clara cells in mouse lung tissue. In contrast, nitrotetrazolium blue reductase activity and CC10 expression declined in culture. Rat type II cells were cultured for 8 days. Between days 0 and 4, the number of type II cells identified by electron microscopy was constant at 70–80%, decreasing to 8% by day 6. In contrast, by day 4, only 42% cells retained alkaline phosphatase activity. BPA and MPA reactivity was altered at day 0 and day 4 respectively, compared with cells in situ. Therefore, the reactivity of lectins analysed here does not reflect functional differentiation status of cultured mouse Clara cells. However, BPA and MPA reactivity may be a sensitive indicator of alterations in rat type II cell differentiation in vitro.