Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Saudi Arabia.
Oxid Med Cell Longev. 2011;2011:365292. doi: 10.1155/2011/365292. Epub 2011 Sep 20.
We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients.
我们使用骨髓 DNA 链断裂、微核形成、精母细胞染色体畸变和精子特征分析等方法，研究了用多种剂量柚皮苷处理的糖尿病大鼠体细胞和生殖细胞中的染色体不稳定性。结果表明，柚皮苷在所有测试剂量下对大鼠既没有细胞毒性也没有遗传毒性。此外，柚皮苷还能显著降低糖尿病诱导的体细胞和生殖细胞中的染色体不稳定性，且呈剂量依赖性。此外，糖尿病诱导了特征性的氧化应激的生化改变，包括脂质过氧化增强、氧化型谷胱甘肽积累、还原型谷胱甘肽减少和细胞内活性氧积累。柚皮苷治疗能剂量依赖性地改善这些生化标志物。总之，柚皮苷对糖尿病诱导的大鼠体细胞和生殖细胞染色体不稳定性具有明显的保护作用，这可能部分是通过减少高血糖诱导的新自由基生成来实现的。因此，柚皮苷可能是降低与高血糖相关的遗传毒性风险的一个很好的候选物，可能会降低继发恶性肿瘤和异常生殖结果的风险，这对糖尿病患者来说尤为重要。
