庄宇, 王彦琴, 帅怡, 孙宇立, 肖萍. α-硫辛酸大鼠90d喂养实验研究[J]. 环境与职业医学, 2012, 29(6): 388-391,394.
引用本文: 庄宇, 王彦琴, 帅怡, 孙宇立, 肖萍. α-硫辛酸大鼠90d喂养实验研究[J]. 环境与职业医学, 2012, 29(6): 388-391,394.
ZHUANG Yu , WANG Yan-qin , SHUAI Yi , SUN Yu-li , XIAO Ping . A 90-Day Oral Toxicity Study of α-Lipoic Acid in Rats[J]. Journal of Environmental and Occupational Medicine, 2012, 29(6): 388-391,394.
Citation: ZHUANG Yu , WANG Yan-qin , SHUAI Yi , SUN Yu-li , XIAO Ping . A 90-Day Oral Toxicity Study of α-Lipoic Acid in Rats[J]. Journal of Environmental and Occupational Medicine, 2012, 29(6): 388-391,394.

α-硫辛酸大鼠90d喂养实验研究

A 90-Day Oral Toxicity Study of α-Lipoic Acid in Rats

  • 摘要:
    目的 观察大鼠经 α-硫辛酸(α-lipoic acid, ALA)较长期喂养后, 对其毒作用特征及所作用的靶器官, 并初步确定未观察到有害作用的最大剂量(NOAEL)。

    方法 取 Sprague-Dawley大鼠 96只, 按体重随机分成 4组, 雌雄各半, 分别给予实验组动物 180、90、45mg/kg的 ALA与 1%羧甲基纤维素钠(CMC-Na)混悬液, 对照组即给予 1%CMC-Na。

    结果 给予 ALA 90 d后, 180 mg/kg ALA组雌性大鼠出现较明显的中毒体征, 死亡动物多达 5只, 谷丙转氨酶及谷草转氨酶与对照组相比升高 2倍以上, 提示肝细胞损伤; 病理组织学同时显示, 180 mg/kg ALA组部分雌性大鼠的肝脏出现不同程度的病变。染毒第 4周开始, 90、180 mg/kg ALA组雄性大鼠的体重出现明显下降。除此以外, 各组雄性大鼠和对照组及 45、90 mg/kg ALA组雌性大鼠血常规、肝功能、肾功能、脏器系数、病理组织学检查均未见异常。

    结论 ALA的可能作用靶器官为雌性大鼠的肝脏。ALA大鼠 90 d喂养实验的 NOAEL雌雄均为 90 mg/kg。

     

    Abstract:
    Objective To investigate the subchronic toxicity of α-lipoic acid (ALA) on rats including target organ and no-observed-adverse-effect-levels (NOAEL).

    Methods A total of 96 Sprague-Dawley rats were randomly divided into 4 groups by body weight, half male and half female. The experimental groups were fed by gavage with suspensions of 180, 90 or 45 mg/kg ALA with 1% sodium carboxymethyl cellulose (CMC-Na), and the vehicle control group were fed with 1% CMC-Na.

    Results After 90 days of ALA treatment, the toxic signs of female rats in the 180 mg/kg ALA group were obvious, with 5 deaths. The alanine transaminase and the aspartate aminotransferase in the 180 mg/kg group were increased by more than 2 fold compared with the controls, indicating liver cell injury was induced. Meanwhile, histopathological examinations showed various lesions in part of the female rats in the 180mg/kg group. From the fourth week of this study, the body weight of male rats in the 90 and the 180mg/kg ALA groups were decreased significantly. In addition, no abnormality of hematological, biochemical and urinalysis determinants, weight coefficient of major organs, and histopathological examinations was found in all groups of male rats, nor in the 45 and the 90 mg/kg ALA groups of female rats.

    Conclusion Liver could be the target organ of ALA by evidences of the study. The NOAEL of ALA in the 90-day oral toxicity study is 90 mg/kg for rats of both genders.

     

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