García-de-la-Asunción J, Gómez-Cambronero L G, Del Olmo M L, Pallardó F V, Sastre J, Viña J
Department of Anaesthesiology and Surgical Critical Care, Hospital Clinic University, Valencia, Spain.
Free Radic Res. 2007 Mar;41(3):330-4. doi: 10.1080/10715760600868537.
A major limitation in the use of AZT for AIDS treatment is the occurrence of side effects, such as leukopenia. The effects of antioxidant vitamins C and E on AZT-induced leukopenia were investigated in mice. Mice were divided into four groups: (1) controls; (2) AZT-treated; (3) treated with AZT plus vitamins C and E; and (4) pre-treated with vitamins and then treated with AZT plus vitamins. Our results demonstrate that AZT causes leukopenia in mice, which was abrogated by administration of vitamins C and E in the pre-treated group. These vitamins prevented the decrease in cellular content induced by AZT in bone marrow and diminished peroxide levels in myeloid precursors in bone marrow. AZT also caused an increase in plasma malondialdehyde and blood oxidized glutathione levels, which was prevented by the administration of antioxidant vitamins. In conclusion, oxidative stress is involved in AZT-induced leukopenia which may be prevented by antioxidant treatment.
使用齐多夫定(AZT)治疗艾滋病的一个主要限制是会出现副作用,如白细胞减少症。研究了抗氧化维生素C和E对AZT诱导的小鼠白细胞减少症的影响。将小鼠分为四组:(1)对照组;(2)AZT治疗组;(3)AZT加维生素C和E治疗组;(4)先给予维生素预处理,然后用AZT加维生素治疗组。我们的结果表明,AZT可导致小鼠白细胞减少症,而在预处理组中给予维生素C和E可消除这种现象。这些维生素可防止AZT诱导的骨髓细胞含量降低,并降低骨髓中髓系前体细胞的过氧化物水平。AZT还导致血浆丙二醛和血液氧化型谷胱甘肽水平升高,而给予抗氧化维生素可防止这种情况。总之,氧化应激与AZT诱导的白细胞减少症有关,抗氧化治疗可能预防这种情况。