抗癌药物阿霉素对雄性大鼠肝、肾、心脏组织抗氧化及超微结构的影响

S. M. Kewedar
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引用次数: 0

摘要

阿霉素是一种众所周知的抗肿瘤药物,已被证明在治疗各种类型的癌症方面是成功的。我以大鼠为模型,评价阿霉素对肝脏、肾脏和心脏组织的抗氧化研究和超微结构的影响。雄性白化大鼠腹腔注射抗癌药物阿霉素1.0 mg/kg体重,每周3次,连续52天。这是总共18剂的数据。对照动物在52天内接受52次生理盐水,每次0.5 ml。与对照组大鼠相比,注射阿霉素的大鼠在最后一次剂量后体重明显下降。在这项研究中,测量了心脏、肾脏和肝脏的重量。除心脏组织外,治疗大鼠上述组织的蛋白质含量均与对照组有显著差异。实验大鼠肾脏谷胱甘肽(GSH)水平(7.946±0.781)与对照组(8.06±0.74)相比没有显著降低,但肝脏谷胱甘肽(GSH)水平(17.095±1.066)与对照组(13.8±1.3)相比无显著升高。此外,阿霉素治疗组的平均GSH水平(7.9462±0.781)明显低于对照组(8.06±0.74)。脂质过氧化(Lpx)和丙二醛(MDA)(脂质过氧化的标志物)在阿霉素治疗组的肝脏器官中的浓度(0.0162±0.00086)与对照组(0.20±0.02)相比明显降低,肾脏中的MDA含量(0.0239±0.0003)与对照组(0.31±0.03)相比降低,产热(0.0398±0.00097)与对照组(47.451±1.708)相比降低。同一组织处理组谷胱甘肽还原酶(GR)水平显著升高。评估谷胱甘肽- s -转移酶(G-S-T)活性,并在阿霉素模型的所有组织中显著升高。注射阿霉素后,上述组织中谷胱甘肽过氧化物酶(GPx)活性均显著降低。阿霉素处理后的大鼠过氧化氢酶(CAT)活性明显升高。在阿霉素治疗组中,肝脏和肾脏组织中细胞色素p450 (CYTp450)水平显著降低,心脏组织中细胞色素p450水平显著升高。阿霉素处理后,大鼠肝脏组织细胞色素b5 (CYTb5)水平较对照组(615±37.0)显著升高(837.177±61.197),肾脏细胞色素b5含量较对照组(2605.5±259.2)显著升高(447.685±35.215)。心肌组织细胞色素b5(165.352±8.7)低于对照组(88±0.4)。结果显示,阿霉素模型大鼠肝组织组织学、超微结构及生化变化均未见明显变化。长期应用阿霉素治疗肾组织在光镜下无明显变化,但电镜下从组织学角度看无变化。
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Effect of the Anticancer Drug Doxorubicin (Adriamycin) on Antioxidant Studies and Ultrastructural Investigation in the Liver, Kidney, and Heart Tissues of Male Rats
Doxorubicin is a well-known antineoplastic agent that has proved to be successful in the treatment of various types of cancer. I used rats as the model to evaluate the effect of doxorubicin on antioxidant studies and ultrastructural investigations in the liver, kidney, and heart tissues. Male albino rats were given 1.0 mg/kg body weight of the anticancer drug doxorubicin intraperitoneally three times a week for 52 days. This was for a total of 18 doses. Control animals received 52 doses of 0.5 ml of saline over 52 days. The body weights of rats injected with doxorubicin experienced a significant decrease after the last dose compared to the control group of rats. In this study, the weights of the heart, kidneys, and liver were measured. Except for cardiac tissues, the protein content in the aforementioned tissues in treated rats was significantly different from the control. Glutathione (GSH) levels in the kidneys of experimental rats were not significantly lower (7.946 ± 0.781) compared to controls (8.06 ± 0.74) but there was a non-significant increase in GSH levels in the liver (17.095 ± 1.066) compared to controls (13.8 ± 1.3). In addition, the mean GSH levels in doxorubicin-treated hearts were significantly lower (7.9462 ± 0.781) compared to controls (8.06 ± 0.74). Lipid peroxidation (Lpx) and malondialdehyde content (MDA), a marker of lipid peroxidation, were found in much lower concentrations in the liver organ of the doxorubicin-treated group (0.0162 ± 0.00086) as compared to (0.20 ± 0.02) controls, and MDA content in the kidney was decreased (0.0239 ± 0.0003) compared to control rats (0.31 ± 0.03), as well as heat production (0.0398 ± 0.00097) compared to (47.451 ± 1.708) controls. Glutathione reductase (GR) levels were significantly elevated in the same tissue treatment group. Glutathione-S-Transferase (G-S-T) activity was assessed and significantly increased in all tissues in the doxorubicin model. Glutathione peroxidase (GPx) activity showed a significant decrease in all the above tissues after doxorubicin injection. The catalase (CAT) activity of doxorubicin was greatly increased in one treated rat. In the doxorubicin-treated group, levels of cytochrome p450 (CYTp450) were significantly decreased in liver and kidney tissue and significantly elevated in heart tissue. After doxorubicin treatment, cytochrome b5 (CYTb5) levels in liver tissues increased significantly (837.177± 61.197) compared to controls (615 ± 37.0), and the contents of cytochrome b5 in rats' kidneys increased significantly (447.685 ± 35.215) compared to controls (2605.5± 259.2). and cytochrome b5 in heart tissues was lower (165.352± 8.7) when compared to controls (88± 0.4). The results showed that there were few obvious changes in histological, ultrastructural, and biochemical changes in liver tissue in the doxorubicin model. Long-term doxorubicin treatment in kidney tissue results in no significant changes at the light microscopic level, but the electron microscopic level reveals no change from a histological point of view.
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