桉叶油毒性及其对环磷酰胺致小鼠骨髓微核及精子畸形的保护作用

目的探讨桉叶油对环磷酰胺(CP)致小鼠遗传毒性的保护作用。方法①毒性实验:小鼠ig给予桉叶油1700,1750,1800,1850和1900mg·kg-1,检测桉叶油的半数致死量(LD50)。另小鼠分别ig给予桉叶油100,200和400mg·kg-1及花生油(阴性对照)组,每天1次,连续5d。阳性对照组ip给予CP40mg·kg-1,每天1次,共给2d。检测小鼠骨髓嗜多染红细胞微核率。30只雄性小鼠,分别ig给予按叶油100,200和400mg·kg-1和花生油,阳性对照组ip给予CP40mg·kg-1,每天1次,连续5d。观察小鼠精子畸形率。②保护作用实验:小鼠按照如下分组给药:CP+桉叶油400,200和100mg·kg-1,花生油+CP,CP组。第4天与阳性对照组一起ip给予CP40mg·kg-1,每天1次。第5天给药后测定小鼠骨髓微核率。30只雄性小鼠按分组,第6天起与阳性对照组一起每天ip给予CP40mg·kg-1,连续5d,实验共10d。测定小鼠精子畸形率。结果①毒性实验:桉叶油的LD50为1824.01mg·kg-1,95%可信限为(1799.48～1851.19)mg·kg-1。桉叶油对小鼠骨髓嗜多染红细胞微核率和精子畸形率无影响。②保护作用实验:桉叶油100,200和400mg·kg-1组的微核率和精子畸形率明显低于未ig给予桉叶油的CP诱发的微核率和精子畸形率(P<0.05)。结论桉叶油对小鼠无明显的遗传毒性,可降低CP所致小鼠骨髓嗜多染红细胞微核率和精子畸形率。

Toxicity of eucalyptus and its protective effect on micronuclear and sperm malformation induced by cyclophosphamide

OBJECTIVE To explore the protective effect of eucalyptus on genetic toxicity in mice treated by cyclophosphamide (CP). METHODS ① Toxicity experiments: (a)The mice were ig given eucalyptus 1700, 1750, 1800, 1850 and 1900 mg·kg^-1 to determine 50% lethal dose(LD₅₀) of eucalyptus (b). Fifty mice in equal genders were randomly divided into 5 groups, 10 mice each: eucalyptus 100, 200 and 400 mg·kg^-1, negative control group(oil) and positive control group (CP). Mice in eucalyptus groups and negative control group were ig given eucalyptus and oil 0.4 ml, respectively once a day, for 5 d, while mice in positive control group were ip given CP 40 mg·kg^-1 from the fourth to the fifth day . All groups were sacrificed on the fifth day. The micronuclear rate in mice was observed by micronucleus test of bone marrow cells of mice. (c) Thirty male mice were randomly divided into 5 groups. Eucalyptus groups and negative control group were treated as (b) mentioned above. Mice in positive control group were ip given CP 40 mg·kg^-1 for 5 d. The genetic toxicity of eucalyptus in mice was studied by sperm shape abnormality test. ② Protecting experiments: (a) Fifty mice were randomly divided into 5 groups. Mice in eucalyptus groups and negative control group were ig given eucalyptus or oil for 5 d, respectively. All groups were ip given CP 40 mg·kg^-1 from the fourth day to the fifth day and sacrificed on the fifth day. The micronuclear rate in mice was observed by micronucleus test of bone marrow cells. (b) Thirty male mice were randomly divided into 5 groups. Mice in 3 eucalyptus groups and negative control group were ig given eucalyptus or oil for 10 d, respectively. From the sixth to the tenth day, all rats were ip given CP and sacrificed on the thirty fifth day after the first administration with CP. The rate of teratospermia in mice was observed by sperm shape abnormality test. RESULTS ① The acute oral LD50 of eucalyptus was 1824.01 mg·kg^-1 and its 95% confidence interval was 1799.48-1851.19 mg·kg^-1. After mice were given eucalyptus, compared with negative control group, the bone narrow micronuclear rate and teratospermia showed no significant difference. ② Eucalyptus 100, 200 and 400 mg·kg^-1 could dramatically decrease bone narrow micronuclear rate and teratospermia induced by CP. CONCLUSION LD₅₀ of eucalyptus is 1824.01 mg·kg^-1 in mice. Eucalyptus shows no genetic toxicity and can restrain genetic toxicity in mice induced by cyclophosphamide.