Department of Anatomy, Melaka Manipal Medical College, Manipal, Karnataka, India.
Indian J Pharmacol. 2011 Jul;43(4):389-92. doi: 10.4103/0253-7613.83107.
Treatment of cancers with cytotoxic agents such as tyrosine kinase inhibiting drugs often, but not always, result in transient to permanent testicular dysfunction. Germ cells are important targets of many chemicals. Most of the drugs are genotoxins and induce irreversible effect on genetic makeup. These mutagenic changes are proportionally related to carcinogenesis. This is alarmingly dangerous in youth and children, since these effects last longer, affecting fertility or forming basis for carcinogenesis. There is paucity of reports on planned studies of imatinib on the testicular function. Hence, the study was planned to assess the effects of imatinib on biochemical markers of testicular functions in male Swiss albino mice.
Male Swiss albino mice were treated with imatinib and sacrificed at the end of first, second, fourth, fifth, seventh, and tenth week after the last exposure to imatinib. The testis were removed, weighed, and processed for biochemical analysis.
The intratesticular testosterone level was significantly (P<0.001) reduced in treated groups and severe effect was observed on week 4 and 5. The intratesticular lactate dehydrogenase (LDH) level was significantly increased by imatinib in all treated groups up to week 5.
Imatinib does affect testosterone and LDH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with imatinib for gastrointestinal tumors and chronic myeloid leukemia.
使用细胞毒性药物(如酪氨酸激酶抑制药物)治疗癌症通常会导致睾丸功能暂时或永久性障碍,但并非总是如此。生殖细胞是许多化学物质的重要靶标。大多数药物是遗传毒性物质,并对遗传物质造成不可逆转的影响。这些诱变变化与致癌作用成比例相关。这在年轻人和儿童中非常危险,因为这些影响持续时间更长,会影响生育能力或为致癌作用奠定基础。关于伊马替尼对睾丸功能的计划性研究报告很少。因此,本研究旨在评估伊马替尼对雄性瑞士白化病小鼠睾丸功能生化标志物的影响。
雄性瑞士白化病小鼠用伊马替尼处理,并在最后一次暴露于伊马替尼后的第一、第二、第四、第五、第七和第十周结束时处死。取出睾丸,称重并进行生化分析。
治疗组的睾丸内睾酮水平显著降低(P<0.001),第 4 周和第 5 周观察到严重影响。伊马替尼治疗组的睾丸内乳酸脱氢酶(LDH)水平显著升高,直至第 5 周。
伊马替尼确实显著影响睾酮和 LDH 水平,但一旦停药,这种影响是可逆的。这一发现可能有助于临床医生为接受伊马替尼治疗胃肠道肿瘤和慢性髓性白血病的年轻生育期患者计划和解决与生育相关的问题。