Edina Horváth

Consequences of subacute intratracheal exposure of rats to cadmium oxide nanoparticles: Electrophysiological and toxicological effects

Cadmium (Cd) is a metal used in various industrial applications, thereby causing exposure to Cd-containing fumes. The submicron-sized particles in the fumes represent an extra risk due to their high mobility within the organism and high surface area. Toxicity of Cd on the liver, kidney and bones is well known, but there are less data on its neurotoxicity. Here, male Wistar rats were treated for 3 and 6 weeks by intratracheal instillation of cadmium oxide nanosuspension. The body weight gain in treated rats was significantly decreased, and in the rats treated with high dose (0.4 mg/kg Cd daily), there was a significant increase in the weight of lungs and thymus. In this group, the spectrum of spontaneous cortical electrical activity was shifted to higher frequencies, the latency of sensory-evoked potentials was lengthened, and the frequency following ability of the somatosensory evoked potential was impaired—even without detectable Cd deposition in the brain. The data support the role of the nano-sized Cd in the causation of nervous system damage and show the possibility of modeling human neurotoxic damage in rats.

Green tea and vitamin C ameliorate some neuro-functional and biochemical signs of arsenic toxicity in rats

Background/objectives: Nervous system damage is one of the consequences of oral exposure to waterborne inorganic arsenic. In this work, the role of oxidative status in the neurotoxicity of arsenic and the possible role of two foodborne antioxidants in ameliorating arsenic-related oxidative stress were investigated. Methods: Male Wistar rats were given 10 mg/kg b.w. of trivalent inorganic arsenic (in the form of NaAsO2), 5 day/week for 6 weeks by gavage, combined with vitamin C solution (1 g/l) or green tea infusion (2.5 g in 500 ml boiled water) as antioxidants given in the drinking fluid. Results: Body weight gain was reduced by arsenic from the second week and the antioxidants had no effect on that. Cortical evoked potentials had increased latency, tail nerve conduction velocity was reduced, and this latter effect was counteracted by the antioxidants. The effect of green tea was stronger than that of vitamin C, and green tea also diminished lipid peroxidation induced by As. There was fair correlation between brain As levels, electrophysiological changes, and lipid peroxidation, suggesting a causal relationship. Discussion: Natural antioxidants might be useful in the protection of the central nervous system against the toxicity of oral As.

Rutin, a flavonoid phytochemical, ameliorates certain behavioral and electrophysiological alterations and general toxicity of oral arsenic in rats

Arsenic affects large populations and attacks, among others, the nervous system. Waterborne or occupational exposure causes electrophysiological alterations and motor disturbances in humans, and analogous effects were found in animals. Certain phytochemicals may be protective against As-caused damages. In the present study it was investigated whether the flavonoid rutin, applied via the drinking water (2 g/L), ameliorates the effects of arsenic given by gavage (10 mg/kg b.w., in form of NaAsO2) on open field motility, evoked cortical and peripheral electrophysiological activity, and body weight gain in adult male Wistar rats. Body weight gain was significantly reduced from the 4th week of the 6 weeks arsenic treatment and this effect was largely abolished by rutin in the combination treatment group. Rats treated by arsenic alone showed decreased open field motility; latency of the cortical evoked potentials increased and peripheral nerve conduction velocity decreased. These functional alterations were also counteracted by co-administration of rutin, and both the antioxidant and the chelating activity of rutin might have contributed to the ameliorative effect. These results are apparently novel and support the potential role of natural agents in preserving human health in a contaminated environment.

Nervous system effects of dissolved and nanoparticulate cadmium in rats in subacute exposure

Cadmium, a toxic heavy metal with various applications in technology, can affect people both by environmental (foodborne) and occupational (inhalation) exposure and can cause nervous system damage. To model this, rats were subacutely treated either with CdCl2 solution per os (3.0 mg kg−1 b.w.) or nanoparticulate CdO2 (particle size ca 65 nm) by intratracheal instillation (0.04 mg kg−1 b.w.) alone or in sequential combination. Nervous system effects were observed at different levels of function (open field behavior, cortical electrical activity, nerve action potential) and some general toxicological indicators were also measured. Three weeks of oral plus one week of intratracheal exposure caused significant reduction of body weight gain and open field motility. Lengthening of latency of sensory evoked potentials, observed in all treated rats, was also the most significant in the group receiving oral plus intratracheal treatment. Conduction velocity of the tail nerve was likewise decreased in all treated groups. Several of the effects pointed to a potentiating interaction between the two forms of Cd. Modeling environmental and occupational Cd exposure by oral and intratracheal application in rats was feasible, with results suggesting serious negative health effects in humans suffering such a combined exposure.

General and Electrophysiological Toxic Effects of Manganese in Rats following Subacute Administration in Dissolved and Nanoparticle Form

In an attempt to model occupational and environmental Mn exposures and their possible interaction, young male Wistar rats were exposed to Mn by oral administration in dissolved form (MnCl2 ·4H2O, 14.84 and 59.36 mg/kg b.w.) and by intratracheal application of MnO2 nanoparticles (2.63 mg/kg b.w.). After 3 and 6 weeks oral, or 3 weeks oral plus 3 weeks intratracheal, exposure, general toxicological, and electrophysiological tests were done. Body weight gain was significantly reduced after 6 and 3 plus 3 weeks exposure, but the effect of the latter on the pace of weight gain was stronger. Organ weights signalized systemic stress and effect on lungs. Changes in evoked electrophysiological responses (cortical sensory evoked potential and nerve action potential) indicated that the 3 plus 3 weeks combined exposure caused equal or higher changes in the latency of these responses than 6 weeks of exposure, although the calculated summed Mn dose in the former case was lower. The results showed the importance of the physicochemical form of Mn in determining the toxic outcome, and suggested that neurofunctional markers of Mn action may indicate the human health effect better than conventional blood Mn measurement.

Behavioral and general effects of subacute oral arsenic exposure in rats with and without fluoride

Consequences of oral arsenic and fluoride exposure on motor behavior and general toxicity were modeled in young adult male rats which received sodium (meta)arsenite (10 mg/kg b.w.), sodium fluoride (5 mg/kg b.w.), and their combination by gavage, once daily, 5 days a week for 6 weeks. After 6 weeks, 6 animals per group were dissected, while the other 6 were kept for 6 more weeks untreated. Body weight, together with food and water consumption, was measured daily. Arsenic, alone or along with fluoride, caused significant decrease in rearing, and increase in immobility and local activity in the open field in the 3rd and 6th week. By the 12th week, these changes mostly diminished. Weight gain, and food and water consumption were significantly reduced by arsenic but normalized post treatment. Fluoride had no own effect and mostly no influence on effects of arsenic. Massive deposition of arsenic in the rats’ blood, cerebral cortex, and liver by the 6th week, and partial elimination by the 12th week, was seen. The results underline the risk of neuro-functional damage by arsenic and call for further investigations.

Neurotoxic effects of subchronic intratracheal Mn nanoparticle exposure alone and in combination with other welding fume metals in rats

Abstract Manganese (Mn) is a toxic heavy metal exposing workers in various occupational settings and causing, among others, nervous system damage. Metal fumes of welding, a typical source of Mn exposure, contain a complex mixture of metal oxides partly in nanoparticle form. As toxic effects of complex substances cannot be sufficiently understood by examining its components separately, general toxicity and functional neurotoxicity of a main pathogenic welding fume metal, Mn, was examined alone and combined with iron (Fe) and chromium (Cr), also frequently found in fumes. Oxide nanoparticles of Mn, Mn + Fe, Mn + Cr and the triple combination were applied, in aqueous suspension, to the trachea of young adult Wistar rats for 4 weeks. The decrease of body weight gain during treatment, caused by Mn, was counteracted by Fe, but not Cr. At the end of treatment, spontaneous and evoked cortical electrical activity was recorded. Mn caused a shift to higher frequencies, and lengthened evoked potential latency, which were also strongly diminished by co-application of Fe only. The interaction of the metals seen in body weight gain and cortical activity were not related to the measured blood and brain metal levels. Fe might have initiated protective, e.g. antioxidant, mechanisms with a more general effect.