RESUMEN
The aim of the present study was to evaluate the radioprotective effect of diltiazem (DTZ) on Swiss albino mice exposed to gamma radiation. In the present study, radioprotective efficacy of DTZ (a calcium channel blocker) was studied against radiation induced haematological and biochemical alterations. Swiss albino mice of 6-8 weeks old were administered diltiazem (100 mg kg(-1) by weight) intraperitoneally prior to whole body gamma-irradiation (7.5 Gy). Radiation exposure resulted in a significant decline in different bone marrow cells (pro- and normoblasts) and blood constituents (erythrocytes, leukocytes, differential leukocyte count, haematocrit, haemoglobin and erythrocyte sedimentation rate). Pro- and normoblasts, erythrocytes, leukocytes, haematocrit and haemoglobin values showed a significant (p<0.0051) decline until day 3, following a gradual recovery from day 7, but normal values were not recorded until 28 days post-exposure. In contrast, erythropoietin levels increased significantly and reached a maximum on day 3. In DTZ pre-treated irradiated animals, a significant increase in pro- and normoblasts, erythrocytes, leukocytes, differential leukocyte count, haematocrit and haemoglobin values, and a significant decrease in erythropoietin values, were observed compared with control. A significant elevation above normal in lipid peroxidation level was recorded in gamma irradiated mice, whereas this increase was considerably less in DTZ pre-treated animals. Similarly, pre-treatment of DTZ caused a significant increase in erythropoietin and glutathione levels in serum in comparison with irradiated animals. From our study it is clear that DTZ provides protection against radiation-induced haematological and biochemical alterations in Swiss albino mice.
Asunto(s)
Diltiazem/uso terapéutico , Rayos gamma/efectos adversos , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Irradiación Corporal Total/efectos adversos , Animales , Evaluación Preclínica de Medicamentos , Eritropoyetina/efectos de la radiación , Glutatión/metabolismo , Enfermedades Hematológicas/etiología , Peroxidación de Lípido , RatonesRESUMEN
During the period of 1998 to 2002, there was an increase in the incidence of antibody-positive pure red cell aplasia (PRCA) in patients receiving subcutaneous administration of EPREX (epoetinum alfa). As part of the investigation of this event, the aqueous formulation containing polysorbate 80, introduced in 1998, facilitated the leaching of small-molecule, aromatic compounds from the uncoated rubber syringe stoppers. The leachables were identified using Liquid Chromatography-Mass Spectroscopy, Electrospray Ionisation-MS/MS, Dithiothreitol reduction, and Hydrogen/Deuterium exchange. The major leachable was identified as a dialkylphenol disulfide, and the majority of the remaining peaks were identified as structural variants containing different numbers of sulfur atoms in the sulfide bridge. In this report, we describe the strategies and experimental designs that were used to overcome the analytical challenges and that led to successful structural identification of the leachables in EPREX pre-filled syringes with uncoated syringe stoppers.