Arriaga-Alba M, Rivera-Sánchez R, Parra-Cervantes G, Barro-Moreno F, Flores-Paz R, García-Jiménez E
Dirección de Investigación y Enseñanza, Hospital Juárez de México, México, D.F., Mexico.
Arch Med Res. 2000 Mar-Apr;31(2):156-61. doi: 10.1016/s0188-4409(00)00046-1.
Quinolone-induced mutagenesis in the Salmonella typhimurium hisG48 strains suggests that these antibiotics are oxygen free radical generators. The use of beta-carotene as antioxidant was evaluated as an alternative to reduce oxidative cell damage in patients who need therapy with nalidixic acid, norfloxacin, or pipemidic acid. The studied beta-carotene (30%), used by pharmaceutical laboratories as dietary complements, was not toxic or mutagenic for the S. typhimurium TA102 strain at a dose equivalent to 1,500 I.U. At the studied concentrations, the evaluated antimutagen did not modify the minimum inhibitory concentration of nalidixic acid, norfloxacin, or pipemidic acid against uropathogenic Escherichia coli strains.
The mutagenic effect of nalidixic acid and norfloxacin against hisG48 strains was inhibited with 1500 I.U. of beta-carotene. The antimutagenic effect of beta-carotene against mutations induced by pipemidic acid was observed even with 150 I.U. of beta-carotene. The antimutagenic effect against mutations induced on S. typhimurium TA102 or TA104 strains was observed only when the aroclor 1254 rat-induced liver S9 mixture was used.
This mutagenic effect was detected only when the strains were exposed to quinolones and the beta-carotene simultaneously with the S9 mixture, suggesting that quinolones induce oxygen free radicals that may be scavenged by beta-carotene.
The antimutagenic effect of this vitamin A precursor is probably due to the active molecule of vitamin A, a desmutagen with the ability of radical capture. A diet rich in beta-carotene or vitamin A could be a good alternative to reduce genotoxic risk to patients being treated with quinolone.
喹诺酮类药物在鼠伤寒沙门氏菌hisG48菌株中诱导的诱变表明，这些抗生素是氧自由基生成剂。评估了使用β-胡萝卜素作为抗氧化剂，以替代减少需要使用萘啶酸、诺氟沙星或吡哌酸进行治疗的患者的细胞氧化损伤。所研究的β-胡萝卜素（30%），制药实验室用作膳食补充剂，在相当于1500国际单位的剂量下，对鼠伤寒沙门氏菌TA102菌株无毒且无致突变性。在所研究的浓度下，评估的抗诱变剂不会改变萘啶酸、诺氟沙星或吡哌酸对尿路致病性大肠杆菌菌株的最低抑菌浓度。
1500国际单位的β-胡萝卜素可抑制萘啶酸和诺氟沙星对hisG48菌株的诱变作用。即使使用150国际单位的β-胡萝卜素，也观察到β-胡萝卜素对吡哌酸诱导的突变具有抗诱变作用。仅当使用艾氏剂1254大鼠诱导的肝脏S9混合物时，才观察到对鼠伤寒沙门氏菌TA102或TA104菌株诱导的突变的抗诱变作用。
仅当菌株与S9混合物同时暴露于喹诺酮类药物和β-胡萝卜素时，才检测到这种诱变作用，这表明喹诺酮类药物诱导的氧自由基可能被β-胡萝卜素清除。
这种维生素A前体的抗诱变作用可能归因于维生素A的活性分子，一种具有自由基捕获能力的去诱变剂。富含β-胡萝卜素或维生素A的饮食可能是降低接受喹诺酮治疗患者遗传毒性风险的良好选择。
