Lipid peroxidation, free radical production and antioxidant status in breast cancer

Lipid peroxidation, free radical production and antioxidant status in breast cancer
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DOI:
10.1023/a:1006357330486
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发表时间:
2000-01-01
影响因子:
3.8
通讯作者:
Husain, SA
Husain, SA
中科院分区:
医学2区
文献类型:
--
作者:
Ray, G;Batra, S;Husain, SA

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活性氧代谢物(ROM),包括超氧阴离子(O-2(.-)),过氧化氢(H 2 O 2)和羟基自由基((OH)-O-),在致癌过程中起重要作用。有一些主要的抗氧化剂,如超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT),防止由ROM引起的细胞和分子损伤。我们进行了本研究,以确定O-2(.-)测定了54例乳腺癌(BC)患者血清中过氧化氢(H2 O2)、丙二醛(MDA)含量,并沿着测定了SOD、GPx和CAT活性。42例年龄和性别相匹配的轻微手术问题患者,无任何肿瘤或乳腺疾病史,作为对照。无论临床分期和绝经状态如何,BC患者的产生量均显著高于对照组(p < 0.001)。同样,H2 O2的生产是显着较高的BC患者,特别是在第三阶段和绝经后组,相比各自的控制。与相应的对照组相比,在II期(p < 0.001)、III期(p < 0.01)、绝经后(p < 0.005)和绝经前(p < 0.02)组中也观察到MDA浓度显著升高。除Ⅳ期GPx活性变化较小外(P <0.02),其余各组SOD、GPx活性均显著升高(P <0.001)。相反,CAT活性被发现在所有研究组中显着抑制。在II期观察到最大抑制(-61.8%)。在我们的研究中,较低的CAT活性可能是ROM,特别是O-2(.-)和(OH)-O-。而SOD和GPx则不受这些较高的ROM产量的影响。我们的研究结果表明,较高的ROMs生产和降低CAT活性,这支持了氧化应激致癌假说。相对较高的SOD和GPx可能是由于血液中ROM产生增加的反应。然而,较高的SOD和GPx活性可能不足以将高水平的H2 O2解毒为H2O,导致形成最危险的(OH)-O-。自由基其次是MDA。因此,CAT的管理可能有助于BC患者的管理。然而,需要进一步的临床研究来评估这种抗氧化酶在BC管理中的作用。
Reactive oxygen metabolites (ROMs), including superoxide anion (O-2(.-)), hydrogen peroxide (H2O2) and hydroxyl radical ((OH)-O-.), play an important role in carcinogenesis. There are some primary antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) which protect against cellular and molecular damage caused by the ROMs. We conducted the present study to determine the rate of O-2(.-) and H2O2 production, and concentration of malondialdehyde (MDA), as an index of lipid peroxidation, along with the SOD, GPx and CAT activities in 54 breast cancer (BC) patients. Forty-two age- and sex-matched patients with minor surgical problems, who had no history of any neoplastic or breast disorders, were taken as controls.The rate of O-2(.-) production was significantly higher (p < 0.001) in BC patients than controls, irrespective of clinical stages and menopausal status. Similarly, H2O2 production was significantly higher in BC patients, especially in stage III and postmenopausal groups, as compared to the respective controls. MDA concentration was also observed significantly elevated in stage II (p < 0.001), stage III (p < 0.01), postmenopausal (p < 0.005), and premenopausal (p < 0.02) group as compared to their corresponding controls. SOD and GPx activities were found significantly raised in all the groups (p < 0.001), except the GPx activity was found a smaller alteration in stage IV (p < 0.02). On the contrary, CAT activity was found significantly depressed in all the study groups. The maximum depression was observed in stage II (-61.8%). Lower CAT activity in our study may be the effect of higher production of ROMs, particularly O-2(.-) and (OH)-O-.. SOD and GPx, however, were less effected by these higher ROMs production. The results of our study have shown a higher ROMs production and decreased CAT activity, which support the oxidative stress hypothesis in carcinogenesis. The relatively higher SOD and GPx may be due to the response of increased ROMs production in the blood. However, the higher SOD and GPx activities may be inadequate to detoxify high levels of H2O2 into H2O leading to the formation of the most dangerous (OH)-O-. radical followed by MDA. Therefore, administration of CAT may be helpful in the management of BC patients. However, further elaborate clinical studies are required to evaluate the role of such antioxidant enzymes in BC management.