RESUMEN
The adult male albino rats were grouped into five groups (control group and four variably treated groups with thorium (Th) in single or successive with or without alginate treatment). The IP administration of thorium nitrate (13.6 mg/kg b.wt.) induced a regional distribution and accumulation ordered as cerebellum > cerebral cortex > brain stem > hippocampus > hypothalamus > striatum. Also, it induces a significant increase in Na+, Ca2+, and Fe3+ ion content and malondialdehyde (MDA) level while K+ ions and glutathione (GSH) level were significantly decreased. On the other hand, the daily oral administration of 5% alginate showed a significant decreasing in the accumulation of thorium in the different brain areas and mitigated its hazardous effects. By the alginate treatment, Na+, Ca2+, Fe3+, and level of MDA were declined while K+ ions and GSH level showed a significant increase. The improvement of the investigated parameters was attributed to the specific chelating, regeneration, and antioxidant properties of the alginate. So, alginate administration could ameliorate the hazardous effects of thorium nitrate.
Asunto(s)
Ácido Algínico/farmacología , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Compuestos de Torio/antagonistas & inhibidores , Administración Oral , Ácido Algínico/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Encéfalo/metabolismo , Masculino , Ratas , Compuestos de Torio/administración & dosificación , Compuestos de Torio/farmacocinética , Distribución TisularRESUMEN
PURPOSE: Thorium ((232)Th), a heavy metal radionuclide that targets the liver and skeleton, has been shown to accumulate in the central nervous system at low levels. The present study was aimed to investigate neurobehavioural and neurochemical changes in mice treated with (232)Th at sub-lethal doses. MATERIALS AND METHODS: Swiss albino mice were administered intraperitoneally with thorium nitrate. The chelation-based therapeutic effect of calcium diethylenetriamine pentaacetate (Ca-DTPA) was tested on the (232)Th-treated mice. (232)Th localisation was determined in brain regions by the Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method. Achetylcholine esterase (AChE) activity in different brain regions was evaluated to assess the cholinergic function of mice CNS. Oxidative damage was evaluated by assessing the activities of antioxidant enzymes (i.e., superoxide dismutase and catalase) and the level of lipid peroxidation. The neurobehavioural alteration in the treated mice was studied by the shuttle box method. RESULTS: (232)Th accumulation found in different brain regions followed the order: Cerebellum (Cbl) > cortex (Ctx) > hippocampus (Hp) > striatum (Str). However, removal of (232)Th by Ca-DTPA was significant from brain regions like Cbl, Ctx and Str but not from Hp. A significant increase in lipid peroxidation and acetylcholine esterase (AChE) activity was observed in the treated mice but activities of superoxide dismutase and catalase was found substantially decreased. (232)Th treatment impaired the learning and memory-based neurobehaviour of the mice. Furthermore, our data suggest that Ca-DTPA injection in (232)Th-treated animals failed to improve the neurobehaviour of the treated mice, perhaps because Ca-DTPA could not decorporate (232)Th or mitigate (232)Th-mediated neurochemical changes effectively from/in hippocampus, a brain region implicated in learning and memory response. CONCLUSION: Administration of (232)Th in mice caused neurobehavioural alteration and impairment of cholinergic function, which might be the consequence(s) of oxidative stress induction in different brain regions.
Asunto(s)
Conducta Animal/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Neuroquímica , Torio/toxicidad , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/metabolismo , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/efectos de la radiación , Conducta Animal/efectos de la radiación , Transporte Biológico , Peso Corporal/efectos de los fármacos , Peso Corporal/efectos de la radiación , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/efectos de la radiación , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Femenino , Inyecciones , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/efectos de la radiación , Ratones , Ácido Pentético/farmacología , Torio/administración & dosificación , Torio/metabolismo , Compuestos de Torio/administración & dosificación , Compuestos de Torio/metabolismo , Compuestos de Torio/toxicidadRESUMEN
We studied histomorphology of the CBA line mice liver after 30 and 90 days of the low dose gamma-radiation influence combined with incorporated Th(NO3)4 in doses 0.03; 0.1; 0.3 grams per kilogram of the living mouse weight. Morphophysiological and morphometric changes were shown. The liver mass and index were significant by increased after 30 days influence. The same changes after 90 days influence were not shown. The morphometric parameters (dynamics of double-nucleus and polyploid hepatocytes, nucleoluses numbers) gave evidence of the liver energy disbalance.
Asunto(s)
Rayos gamma/efectos adversos , Hígado/patología , Traumatismos Experimentales por Radiación/patología , Contaminantes Radiactivos del Suelo/administración & dosificación , Compuestos de Torio/administración & dosificación , Animales , División Celular/efectos de la radiación , Núcleo Celular/patología , Núcleo Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Hígado/efectos de la radiación , Regeneración Hepática/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos CBA , Traumatismos Experimentales por Radiación/etiología , Contaminantes Radiactivos del Suelo/toxicidad , Compuestos de Torio/toxicidadRESUMEN
1. With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 228Th nitrate from the rat after subcutaneous (sc) and intramuscular (im) injection to simulate wound contamination. The commencement of treatment was delayed 30 min, 6 h or 1 d and the animals killed at 7 d. 2. In all cases 3,4,3-LIHOPO was appreciably more effective than DTPA although the efficacy of treatment and the relative effectiveness of the ligands decreased rapidly with their delay in administration. 3. Optimum removal with both ligands occurred when initial local administration at 30 min after exposure was followed by repeated intraperitoneal injection at 6 h, 1, 2 and 3 d. Under these conditions the body content of 228Th was reduced to 20% of controls after sc injection and 15% after im injection. The corresponding values using repeated DTPA administration were 80% and 54%. 4. It is concluded that 3,4,3-LIHOPO represents, potentially, a considerable advance on DTPA, the current agent of choice for the treatment of wounds contaminated by 228Th.