Aleisa A M, Al-Rejaie S S, Bakheet S A, Al-Bekari A M, Al-Shabanah O A, Al-Majed Abdulhakeem, Al-Yahya Abdulaziz A, Qureshi S
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Mutat Res. 2007 Dec 1;634(1-2):93-100. doi: 10.1016/j.mrgentox.2007.06.005. Epub 2007 Jun 27.
Diabetes mellitus (DM) is a chronic disease that is characterized by deteriorating glycemic control. The disease is known to be caused by imbalance between reactive oxygen species (ROS) and antioxidant defense systems. Hyperglycemia is commonly observed in a wide variety of diseases, including cancer. Although, therapy against glycemic control, is used in all these diseases, the diabetic cancer patients are on additional therapy with anticancer drugs. The objective of present study was to study if Glucophage (metformin), a very popular antidiabetic agent can avert the mutagenicity and lipid peroxidation caused by adriamycin (ADR), which is a commonly used cytotoxic drug. The experimental protocol included oral treatment of mice with different doses (62.5, 125 and 250 mg/kg day) of metformin for 7 days. Some mice in each group were injected i.p. with ADR (15 mg/kg). In each case animals were killed, 30 or 24, 48 and 72 h after the last treatment and femurs were excised for cytological studies by micronucleus test. Additional experiments on estimation of glutathione (GSH) and malondialdehyde (MDA) were undertaken in blood and serum, respectively. Twenty-four hour after the treatment, blood from each mouse was collected from heart and preserved for analysis. The results obtained revealed that pretreatment with metformin: (i) reduced the ADR-induced frequency of micronuclei without any alteration in its cytotoxicity and (ii) protected against the ADR-induced increase and decrease of MDA and GSH, respectively. The exact mechanism of action is not known, however, the inhibition of ADR-induced clastogenicity and lipid peroxidation by metformin may be attributed to the antioxidant action of the latter. Our results demonstrate that metformin might be useful to avert secondary tumor risk by decreasing the accumulation of free radicals and inhibition of mutagenicity.
糖尿病（DM）是一种以血糖控制恶化特征的慢性疾病。已知该疾病由活性氧（ROS）与抗氧化防御系统之间的失衡引起。高血糖在包括癌症在内的多种疾病中普遍存在。尽管在所有这些疾病中都采用了血糖控制疗法，但糖尿病癌症患者还需接受抗癌药物的额外治疗。本研究的目的是探究一种非常受欢迎的抗糖尿病药物二甲双胍是否可以避免由常用细胞毒性药物阿霉素（ADR）引起的致突变性和脂质过氧化。实验方案包括用不同剂量（62.5、125和250毫克/千克/天）的二甲双胍对小鼠进行口服治疗7天。每组中的一些小鼠腹腔注射阿霉素（15毫克/千克）。在每种情况下，在最后一次治疗后的30或24、48和72小时处死动物，并切除股骨进行微核试验的细胞学研究。分别在血液和血清中进行了关于谷胱甘肽（GSH）和丙二醛（MDA）估计的额外实验。治疗24小时后，从每只小鼠的心脏采集血液并保存用于分析。获得的结果表明，二甲双胍预处理：（i）降低了阿霉素诱导的微核频率，而其细胞毒性没有任何改变；（ii）分别防止了阿霉素诱导的MDA增加和GSH减少。确切的作用机制尚不清楚，然而，二甲双胍对阿霉素诱导的断裂形成性和脂质过氧化的抑制作用可能归因于后者的抗氧化作用。我们的结果表明，二甲双胍可能通过减少自由基的积累和抑制致突变性来避免继发性肿瘤风险。
