Rabbani Syed Imam, Devi Kshama, Khanam Salma
Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore-560 027.
Clin Med Oncol. 2008;2:423-9. doi: 10.4137/cmo.s678. Epub 2008 May 19.
Hyperglycemia is the main determinant of long term diabetic complications mainly through induction of oxidative stress responsible for secondary defects including cancer, infertility etc. Thiazolidinediones (TZDs) are known to posses the antioxidant potential against the reactive oxygen species. The ability of clinically used TZDs like Rosiglitazone (RSG) and Pioglitazone (PIO) in diabetic complications is still need to be studied extensively in the literature. In this study, the role of RSG and PIO on the frequency of nuclear and germinal cell damage was studied using bone marrow micronucleus (MN) test, sperm shape abnormality and sperm count in normal animals. The drugs were tested in the three doses (1, 10 and 100 mg/kg) after acute (48 hrs and 72 hrs) and chronic (4 weeks) treatment. The results indicated that RSG has produced significant (p < 0.01) decrease in P/N (polychromatic and normochromatic erythrocytes) ratio at 10 and 100 mg/kg without affecting the frequency of micronucleated erythrocytes, sperm shape morphology and sperm count. PIO in the tested doses did not induce any change in P/N ratio and sperm count but the higher dose (100 mg/kg) showed suppression of MN in normochromatic erythrocytes and % sperm shape abnormality compared to the control group.
高血糖是糖尿病长期并发症的主要决定因素,主要是通过诱导氧化应激,而氧化应激会导致包括癌症、不育等在内的继发性缺陷。噻唑烷二酮类药物(TZDs)已知具有对抗活性氧的抗氧化潜力。临床上使用的TZDs如罗格列酮(RSG)和吡格列酮(PIO)在糖尿病并发症中的作用在文献中仍需广泛研究。在本研究中,使用骨髓微核(MN)试验、精子形态异常和正常动物的精子计数,研究了RSG和PIO对核细胞和生殖细胞损伤频率的影响。在急性(48小时和72小时)和慢性(4周)治疗后,以三种剂量(1、10和100毫克/千克)对药物进行测试。结果表明,RSG在10和100毫克/千克时使P/N(多色和正色红细胞)比值显著降低(p < 0.01),而不影响微核红细胞的频率、精子形态和精子计数。测试剂量的PIO未引起P/N比值和精子计数的任何变化,但与对照组相比,较高剂量(100毫克/千克)显示正色红细胞中的MN受到抑制,精子形态异常百分比降低。