Norepinephrine protects mice from acute lethal doses of carboplatin.

摘要: We demonstrated in previous studies that adrenergic agents may affect hematopoiesis via high- and low-affinity alpha1-adrenoceptors present on bone marrow (BM) cells [1-3]. Here we show norepinephrine administration mice rescued from the toxic effect of non-cell cycle specific chemotherapeutic agent, carboplatin. Protection granulocyte/macrophage colony-forming units (GM-CFUs) was already apparent only a few hours after carboplatin administration. On day 3, hematopoietic rescue reflected by higher leukocyte platelet counts. At its most effective dose (3 mg/kg, subcutaneously injected), protected 77% previously injected intravenously with 200 mg/kg (LD 100: 170 mg/kg). Simultaneous alpha1-adrenoceptor antagonist prazosin reduced percentage surviving to 30%, indicating mediated norepinephrine-induced rescue. Consistently, also blood counts GM-CFUs. In vitro, (1 microM) GM-CFUs BM cells, although this counteracted low concentrations (0.1-10 nM) prazosin. Our findings indicate undescribed novel mechanism regulation find application preventing myeloablative anticancer treatments.