RESUMEN
Occupational exposure to beryllium may cause chronic beryllium disease (CBD), a granulomatous interstitial pneumonitis caused by a cell-mediated immune response with delayed hypersensitivity initiated by an electrostatic interaction with the MHC class II human leukocyte antigen (HLA). Increased research efforts focus on the development of a CBD treatment by chelation therapy. This work presents an in vitro evaluation of the beneficial effects of beryllium chelation with different organic substrates. We have used a standard beryllium lymphocyte proliferation test (BeLPT) adapted for mouse splenocytes. Three complexing agents, 4,5-dihydroxy-1,3-benzenedisulfonic acid (tiron), nitrilotripropionic acid (NTP) and nitrilotriacetic acid (NTA), were tested using different protocols of the splenocyte proliferation test (SPT). We studied their corrective effect (beryllium pre-exposed splenocytes), their protective effect (ligand pre-exposed splenocytes) and their combined effects at fixed Be:L ratio of 1:2, at fixed Be concentration and at fixed L concentration. We also studied the effect of tiron in preventing splenocyte sensitization to beryllium. All three complexing agents showed a corrective effect and proved efficient in the combined effects, except NTA in the fixed Be:L ratio. Only NTP and tiron showed a significant protection at lower beryllium concentrations, while NTA was not significant. Splenocytes pre-exposed to chelated beryllium did not show sensitization while splenocytes pre-exposed to beryllium were sensitized. We observed a strong correlation between the efficiency of the complexing agent and its affinity towards beryllium. Both tiron and NTP showed a similar affinity towards the beryllium ion that is 10(7) higher than that of NTA.
Asunto(s)
Beriliosis/inmunología , Berilio/toxicidad , Quelantes/farmacología , Bazo/efectos de los fármacos , Sal Disódica del Ácido 1,2-Dihidroxibenceno-3,5-Disulfónico/química , Sal Disódica del Ácido 1,2-Dihidroxibenceno-3,5-Disulfónico/farmacología , Animales , Beriliosis/prevención & control , Berilio/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Quelantes/química , Relación Dosis-Respuesta a Droga , Femenino , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ácido Nitrilotriacético/química , Ácido Nitrilotriacético/farmacología , Bazo/patologíaRESUMEN
The efficacy of Tiron and calcium disodium EDTA in the treatment of experimental beryllium intoxication was investigated in rats. Beryllium nitrate was administered intramuscularly (50 mg kg(-1)) once only, provoking duration-dependent changes. Maximum changes were recorded after a 7-day regimen. Considerable inhibition was recorded in protein and glycogen contents, as well as in the activity of alkaline phosphatase, glucose-6-phosphatase, acid phosphatase and lipid peroxidation. These parameters were restored considerably with chelation therapy, but comparatively Tiron offered better protection. These findings were further confirmed by atomic adsorption spectrophotometry. Tiron was found to be significantly more effective than CaNa(2)EDTA in reducing the beryllium concentration in the liver, kidney and lungs.
Asunto(s)
Beriliosis/prevención & control , Berilio/toxicidad , Quelantes/uso terapéutico , Sal Disódica del Ácido 1,2-Dihidroxibenceno-3,5-Disulfónico/uso terapéutico , Análisis de Varianza , Animales , Beriliosis/metabolismo , Berilio/farmacocinética , Modelos Animales de Enfermedad , Ácido Edético/uso terapéutico , Femenino , Radioisótopos/toxicidad , Ratas , Ratas Sprague-DawleyRESUMEN
An ayurvedic medicine, Liv-52, was studied as a prophylactic agent against beryllium-induced toxicity in rats. Administration of beryllium per se caused severe degenerative and necrotic changes in kidneys, liver, and uterus. Beryllium exposure also reduced glycogen content, activities of alkaline phosphatase, succinate-dehydrogenase, and adenosine-triphosphatase in these organs. On the contrary, activities of acid phosphatase and glucose-6-phosphatase showed marginal increase. Liv-52-primed rats exhibited comparatively less marked toxic effects.