RESUMEN
BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. MATERIALS AND METHODS: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m(3) for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h. RESULTS: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. CONCLUSION: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs.
Asunto(s)
Antiinfecciosos Locales/toxicidad , Compuestos de Benzalconio/toxicidad , Pulmón/patología , Animales , Peso Corporal/efectos de los fármacos , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocina CXCL2/análisis , Quimiocinas CC/análisis , Ingestión de Alimentos/efectos de los fármacos , Femenino , Inmunoglobulina E/análisis , Exposición por Inhalación , Interleucina-6/análisis , Recuento de Leucocitos , Ratas WistarRESUMEN
BACKGROUND: Organophosphates are cholinesterase (ChE) inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours) rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP) poisoning symptomatology. In rodents, corticosterone (CORT) is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentration (the CORT response) and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET) [2-methyl-1,2-di(pyridin-3-yl)propan-1-one] blocks CORT synthesis by inhibiting steroid 11ß-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP) [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. MATERIAL AND METHODS: The purpose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. CONCLUSION: The following was observed in the MET-treated rats: i) no rise in plasma CORT concentration after the CVP administration, ii) a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.
Asunto(s)
Clorfenvinfos/toxicidad , Inhibidores Enzimáticos/uso terapéutico , Insecticidas/toxicidad , Metirapona/uso terapéutico , Intoxicación por Organofosfatos/prevención & control , Animales , Inhibidores de la Colinesterasa/toxicidad , Colinesterasas/metabolismo , Corticosterona/sangre , Masculino , Ratas , Ratas Wistar , Esteroide 11-beta-Hidroxilasa/antagonistas & inhibidoresRESUMEN
OBJECTIVES: Exposure to various stressors is known to result in sensitization to psychostimulants, a state related to the psychostimulant dependence and addiction. It has been shown in some studies that the rise in corticosterone (CORT) concentration is indispensable for both the induction and the expression of behavioral sensitization. Therefore, it might be suspected that behavioral hyposensitivity to amphetamine (AMPH) is somehow related to a reduced CORT response to the psychostimulant subsequent to the chlorphenvinphos (CVP) intoxication. MATERIALS AND METHODS: The male adult Wistar rats received single i.p. injections of CVP at the doses 0.5, 1.0 or 3.0 mg/kg b.w., or pure corn oil. CORT concentration was determined in samples of blood drawn from the tail vein before and then 30, 60, 180 min and 24 h after injection. The other rats were divided into two groups and tested, three weeks after the CVP injection for the effect of AMPH (0.5 mg/kg b.w. i.p.) on the serum CORT concentration. In addition, behavioral sensitivity to AMPH was assessed by measuring locomotor activity of the animals in an open-field. RESULTS: 1) The stressor property of CVP was confirmed. The injection resulted in up to tenfold increase in the serum CORT concentration. The magnitude and duration of this response were dose-related. 2) Three weeks after the CVP exposure, the CORT response to AMPH was significantly increased. 3) The behavioral response to the psychostimulant, i.e. augmented locomotion, was significantly reduced compared to the control. CONCLUSIONS: The results confirm that CVP exposure causes behavioral hyposensitivity to AMPH. This effect, however, could not be ascribed to a diminished CORT response.
Asunto(s)
Anfetamina/farmacología , Conducta Animal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Clorfenvinfos/toxicidad , Insecticidas/toxicidad , Animales , Corticosterona/sangre , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
OBJECTIVES: Some data suggest that increased behavioural sensitivity to psychostimulants may develop after exposure to volatile chemicals in common use. The purpose of the present experiment was to find out whether and in what way inhalation exposure to pseudocumene (PS) or hemimellitene (HM) at low concentrations alters behavioural sensitivity to the psychostimulant amphetamine (AMPH), and propensity to develop behavioural sensitization to AMPH. MATERIAL AND METHODS: Adult male Wistar rats were exposed 6 h/day, 5 days a week for 4 weeks to PS or HEM at 0, 25, 100 or 250 ppm. Behavioural sensitivity to AMPH was assessed by measuring locomotor activity of the animals in an open-field. Behavioural sensitization to AMPH was induced by a repeated AMPH treatment. RESULTS: In rats exposed to HEM, the behavioural sensitivity to AMPH was increased, but remained unchanged in rats exposed to PS. The second testing revealed an augmented behavioural response to AMPH in control rats. In the HM exposed rats this augmenting was significantly more evident and in the PS exposed rats significantly less evident than in controls. For each of the two solvents, the concentration-effect relationship was nonlinear; out of the three concentrations used, 100 ppm was the most effective. CONCLUSIONS: The results confirm that low-level inhalation exposure to trimethylbenzene isomers may induce behavioural sensitisation and/or increase the susceptibility of the animals to develop this state upon repeated psychostimulant treatment. They show, however, that HM and PS differ markedly in their ability to induce such alterations.
Asunto(s)
Anfetamina/toxicidad , Conducta Animal/efectos de los fármacos , Derivados del Benceno/toxicidad , Estimulantes del Sistema Nervioso Central/toxicidad , Exposición por Inhalación/efectos adversos , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas WistarRESUMEN
OBJECTIVES: The aim of the study was to obtain quantitative data on the effect of inhalation exposure to benzalkonium chloride (BAC) on the concentration of catecholamines and their metabolites in selected brain structures. Additionally, concentration of corticosterone (CORT) in plasma was estimated. MATERIAL AND METHODS: Wistar rats were subjected to a single (6-hour) or repeated (3 days, 6 h/day) exposure to BAC aerosol at ca. 30 mg/m3. The Waters integrated analytical system of HPLC was used to determine the plasma corticosterone. Qualitative and quantitative determinations of catecholamines and their metabolites: 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic (HVA) acids were performed with the use of the Waters integrity HPLC. RESULTS: The determinations have shown that in the BAC-exposed rats the plasma CORT concentration was several times higher than in the control rats. A significant increase of the concentration of dopamine (DA) (striatum and diencephalon) and noradrenaline (NA) (hippocampus and cerebellum) and a significant reduction of adrenaline (A) level (cortex, hippocampus, striatum and mesencephaloon) was found to occur in the brain of rats exposed to BAC compared to control. In the animals exposed to BAC, the concentration of DOPAC, a DA metabolite, was significantly reduced, but the change occurred mainly in the striatum. This resulted in a significant decrease of the DOPAC/DA and HVA/DA metabolic ratio in this structure. CONCLUSION: It is assumed that the alterations in the concentration of catecholamines and their metabolites in the BAC-exposed rats were related to the unexpectedly strong and persistent activation of the hypothalamo-pituitary-adrenocortical (HPA) axis evidenced by the high plasma CORT concentration.
Asunto(s)
Compuestos de Benzalconio/toxicidad , Encéfalo/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Aerosoles , Animales , Cromatografía Líquida de Alta Presión , Cuerpo Estriado/metabolismo , Corticosterona/sangre , Dopamina/metabolismo , Epinefrina/metabolismo , Femenino , Ácido Homovanílico/metabolismo , Exposición por Inhalación , Norepinefrina/metabolismo , Ratas , Ratas Wistar , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) with a C8 to C18 chain length of alkyl groups. Since BAC exerts toxic effects on microorganisms, it has been used as an effective germicide and preservative, mostly in cosmetic industry and medicine. However, the toxic potential of BAC may be hazardous to humans, due to the common use of preparations containing BAC as a preservative. MATERIAL AND METHODS: To assess the possible toxic effects of BAC, two-stage experiments were performed on female Wistar rats. At first, LC50 after a single exposure to BAC aerosol was determined. Then, the animals were exposed to BAC aerosol at 30 mg/m3 for 6 h, and for 3 days (6 h/day). The controls were unexposed rats. Directly after BAC exposure and 18 h afterwards, BALF concentrations were measured of total protein, Clara cell protein, matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), immunoglobulin E (IgE) and cytokines (TF-alpha, IL-6 and MIP-20), lactate dehydrogenase (LDH) and GSH-S-transferase (GST). RESULTS: The LC50 value for exposed rats was ca. 53 mg BAC in m3 air for 4 h. All the rats survived single and repeated inhalation exposure to 30 mg/m3 BAC. After single and repeated exposure, lung weight, total protein, HA and LDH activity in BALF of exposed rats were higher than in controls while CC16 levels were decreased. A significantly higher BALF concentration of IL-6 and IgE was noted in animals exposed to single and repeated doses. BALF concentrations of MMP-9, TNF-alpha, and MIP-2 in exposed rats were similar to those in control animals. CONCLUSION: BAC may be classified to class I acute inhalation toxicity. It showed a strong inflammatory and irritant activity on the lungs after 6h inhalation and stimulated dynamic patterns of IL-6 and IgE production and protein infiltration from blood vessels to BALF. Continued exposure resulted in cellular destruction, a statistically significant increase in LDH activity and a continuous decrease in CC16 concentration in BALF.