László Nagymajtényi

A study on behavioral, neurotoxicological, and immunotoxicological effects of subchronic arsenic treatment in rats.

Male Wistar rats were treated for 4, 8, and 12 wk with 3.33, 6.66, 13.3, or 26.6 mg/kg of inorganic arsenic (NaAsO 2 ) per os by gavage. Changes in behavioral and electrophysiological parameters (spontaneous open-field exploration; electrocorticogram mean frequency and power spectrum; latency and duration of somatosensory, visual, and auditory evoked potentials; conduction velocity; and relative and absolute refractory period of a peripheral nerve) were determined. Treated rats exhibited hypoactivity of horizontal ambulation in the open field and showed depressed rates of grooming. The electrophysiological data, recorded from anesthetized rats, did not show any significant dose- and time-dependent changes. Changes in humoral immune response, tested after 4 wk of treatment, were not marked. The weight of organs responsible for immune response (thymus, spleen, adrenals), was significantly reduced, as were delayed-type hypersensitivity (DTH) reaction and mean cell volume (MCV) of red blood cells a hematological parameter. Plaque-forming cell (PFC) assay proved to be insensitive in this short-time exposure. These results suggest that subchronic low-level exposure to arsenic can affect immune responses and/or spontaneous behavior of rats.

Behavioural and functional neurotoxicological changes caused by cadmium in a three-generational study in rats.

1 Three consecutive generations of Wistar rats were orally treated by gavage with 3.5, 7.0 or 14.0 mg/kg cadmium (in form of cadmium chloride diluted in distilled water) over the period of pregnancy, lactation and 8 weeks after weaning. 2 Behavioural (open field behaviour) and electrophysio logical (spontaneous and evoked cortical activity, etc.) parameters of male rats from each generation were investigated at the age of 12 weeks. 3 The main behavioural outcomes were change in vertical exploration activity (rearing) and increased exploration of an open field centre. The spontaneous and evoked electrophysiological variables showed dose- and generation-dependent changes (increased frequencies in the electrocorticogram, lengthened latency and duration of evoked potentials, etc.) signalling a change in neural functions. 4 The data show that low-level, multigeneration expo sure to inorganic cadmium can affect functions of the nervous system. This suggests that cadmium exposed human populations may be at risk of developing nervous system disorders.

Behavioral and neurotoxicological effects of subchronic manganese exposure in rats.

In male Wistar rats, behavioral and electrophysiological investigations, and blood and brain manganese level determinations, were performed; during 10 weeks treatment with low-dose manganese chloride and a 12 weeks post-treatment period. Three groups of 16 animals each received daily doses of 14.84 and 59.36mg/kg b.w. MnCl(2) (control: distilled water) via gavage. During treatment period, Mn accumulation was seen first in the blood, then in the brain samples of the high-dose animals. Short- and long-term spatial memory performance of the treated animals decreased, spontaneous open field activity (OF) was reduced. The number of acoustic startle responses (ASR), and the pre-pulse inhibition (PPI) of these, diminished. In the cortical and hippocampal spontaneous activity, power spectrum was shifted to higher frequencies. The latency of the sensory evoked potentials increased, and their duration, decreased. By the end of the post-treatment period, Mn levels returned to the control in all samples. The impairment of long-term spatial memory remained, as did the number of acoustic startle responses. Pre-pulse inhibition, however, returned to the pre-treatment levels. The changes of the open field activity disappeared but a residual effect could be revealed by administration of d-amphetamine. The electrophysiological effects were partially reversed. By applying a complex set of methods, it was possible to obtain new data for a better-based relationship between the known effects of Mn at neuronal level and the behavioral and electrophysiological outcomes of Mn exposure.

Nervous system effects in rats on subacute exposure by lead-containing nanoparticles via the airways

Context and objective: Lead (Pb) is a heavy metal harmful for human health and environment. From leaded gasoline (still used in certain countries), and in Pb processing and reprocessing industries, airborne particles are emitted which can be inhaled. In such exposure, the size of particles entering the airways is crucial. The nervous system is a primary target for Pb, and consequences like occupational neuropathy and delayed mental development of children are well-known. The aim of this work was to investigate the neurotoxicity of Pb nanoparticles (NPs) applied into the airways of rats. Methods: Nano-sized lead oxide particles (mean diameter ca. 20 nm) were suspended in distilled water and instilled into the trachea of adult male Wistar rats (in doses equivalent to 2 and 4 mg/kg Pb), 5 times a week for 3 and 6 weeks. At the end, open field motility was tested, then central and peripheral nervous activity was recorded in urethane anesthesia. Results and conclusion: The treated rats’ body weight gain was significantly lower than that of the controls from the 3rd week onwards, and the weight of their lungs was significantly increased. Horizontal motility increased while vertical motility decreased. Spontaneous cortical activity was shifted to higher frequencies. The somatosensory cortical evoked potential showed increased latency and decreased frequency-following ability, and similar alterations were seen in the tail nerve. Significant Pb deposition was measured in blood, brain, lung and liver samples of the treated rats. The experiments performed seem to constitute an adequate model of the human effects of inhaled Pb NPs.

Accumulation of aluminum in rat brain: Does it lead to behavioral and electrophysiological changes?

The present study was undertaken to examine possible aluminum (Al) accumulation in the brain of rats and to investigate whether subchronic exposure to the metal leads to behavioral and neurophysiological changes in both treated and control groups. Each of the groups consisted of 10 animals. Aluminum chloride (AlCl3) at a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by gavage for 8 wk. Al-free water by gavage was given to the control group throughout the experiment. Behavioral effects were evaluated by open-field (OF) motor activity and by acoustic startle response (ASR). Electrophysiological examination was done by recording spontaneous activity and sensory-evoked potentials from the visual, somatosensory, as well as auditory cortex. The Al content of each whole brain was determined by electrothermal atomic absorption spectrophotometry. Subchronic Al exposure slightly caused some changes in the evoked potentials and electrocorticograms and in the OF and ASR performance, but these results were not statistically significant. The brain Al levels of the control and the low and high dose of Al-exposed groups were measured as 0.717±0.208 µg/g (wet weight), 0.963±0.491 µg/g (wet weight) and 1.816±1.157 µg/g (wet weight), respectively.

Immunotoxicological effects of repeated combined exposure by cypermethrin and the heavy metals lead and cadmium in rats

The immunotoxic effect of a 28 days oral exposure by 55.4, 22.2, and 11.1 mg/kg cypermethrin (CY) was investigated in 4 weeks old male Wistar rats. The applied test system involved the determination of general toxicological parameters (body weight gain, organ weight of thymus, heart, lung, liver, spleen, kidneys, adrenals and the popliteal lymph node), haematological parameters (white blood cell count, red blood cell count, haematocrit, mean cell volume of red blood cells, cellularity of the femoral bone marrow), as well as immune function assays (splenic plaque forming cell assay, delayed type hypersensitivity reaction). The highest dose resulted in a significant increase of the relative liver weight, and all three doses resulted in (although inconsistent) changes in the haematocrit and MCV values. The maximum of DTH reaction decreased at all three doses. On combination of the highest CY dose with non-effective doses of lead or cadmium the immunotoxic effects of the former were modified. When immunotoxic doses of Cd or Pb were combined with the lowest CY dose, further interactions were observed on the examined parameters. The alterations of the immunotoxic effects of CY by simultaneous exposure with Cd or Pb, as described here, can lead to unexpected health consequences and/or can lead to false positive or negative results in human epidemiological studies.

Smoking behaviour and attitudes of Hungarian Roma and non-Roma population towards tobacco control policies

ObjectivesTo assess the smoking status and support for tobacco control policies among the Roma minority compared with the non-Roma population in Hungary.MethodsA cross-sectional survey was delivered among Roma minority and local non-Roma population; 83 Roma and 126 non-Roma people were interviewed. Chi-square tests and logistic regression were applied to compare Roma and non-Roma populations.ResultsThe prevalence of smoking was significantly higher and the support for tobacco control measures was significantly lower in the Roma population. This effect of ethnicity on attitudes toward tobacco control was explained somewhat, but not completely, by the Roma group’s higher rate of smoking and lower level of education.ConclusionsTobacco control policies are a proven strategy for denormalizing smoking and discouraging initiation. This strategy has important potential for Roma communities because of their high rates of tobacco use. However, this study shows that the Roma are resistant the efforts to limit smoking. Changing these attitudes will require targeted public health interventions that take into account not only the lower educational levels of the Roma, but also their cultural beliefs regarding tobacco.

Preconceptional and prenatal predictors of folic acid intake in Hungarian pregnant women

OBJECTIVE The purpose of the study was to determine demographic, obstetric and pregnancy care related factors of folic acid intake during preconceptional and prenatal period of pregnancy. STUDY DESIGN A questionnaire-based retrospective study was delivered at the Department of Obstetrics and Gynecology and Pregnancy Care Centre. The frequency of folic acid intake was measured before and during pregnancy in 349 pregnant women. RESULTS Factors influencing preconceptional folic acid consumption were planning of pregnancy, previous infertility therapy, multivitamin intake before pregnancy, and folic acid intake during pregnancy. Probability of taking folic acid during pregnancy increased with age, and decreased with gestational age. Earlier detection of pregnancy corresponded to a higher chance of folic acid intake. Prenatal folic acid intake significantly related to the earlier intake of folic acid, and prenatal multivitamin medication. CONCLUSION It is important to target women who are less likely to take periconceptional folic acid as well as to increase awareness of women of childbearing age in general through an intensive campaign and improved education.

Neurophysiological markers as early signs of organophosphate neurotoxicity

The central and peripheral nervous system effects of acute and subchronic exposure to three organic phosphoro-acid esters (dimethoate, dichlorvos, parathion-methyl) were studied. CNS-dependent variables included mean EEG amplitude, mean frequency of the EEG, and the activity (power density) of six component frequency bands. Peripheral nervous system evaluations included determinations of conduction velocity, and both relative and absolute refractory periods. Cholinesterase activity was measured in blood, brain and other organs. The results indicate that acute large doses of these agents produce substantial changes in these measures of CNS and PNS function. In subchronic experiments it was found that a six weeks administration of 1/50 LD50 of the chemicals induced early functional changes in both the central and the peripheral nervous systems. It is recommended that when cholinesterase inhibition is detected in humans, functional evaluations of CNS and PNS should follow.

Behavioral effects of subchronic intoxication with parathion-methyl in male Wistar rats

The behavioral effects of subchronic exposure of male Wistar rats to the organophosphorus compound parathion-methyl (for 6 weeks 1/50 or 1/100 of LD50, PO) were studied. Open-field (OF) and elevated plus-maze (EPM) tasks were used to decide whether or not the compound can affect behavior. Significant effects were measured in the OF activity during the first minute, on the activity of crossing outer squares, increasing latencies to leave center, start of rearing, grooming, and defecation. EPM parameters showed an increased amount of time spent in the open arms and a clear tendency to enter more frequently open arms. The defecation rate in the EPM was significantly decreased. Results are discussed in terms of effects on emotional behavioral components (arousal) and on physiological functioning of the peripheral nervous system (lengthening of latencies).