他莫昔芬对氧化应激诱导的成年母兔心肌细胞损伤及补锌对氧化应激的消除作用

Mohammed Ali, S. M., Ahmed E. Abood
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摘要

他莫昔芬(TAM)自1977年获得美国食品和药物管理局批准以来,一直用于乳腺癌化疗。然而,TAM治疗伴随着心肌细胞凋亡。氧化应激和炎症是TAM细胞凋亡的主要机制。在这项研究中,我们探讨了锌(Zn)的补充是否可以预防tam诱导的成年雌性兔心肌细胞损伤。锌组家兔口服锌(0.3 mg/ kg体重/天,连用42 d),他莫昔芬组家兔口服锌(0.25 mg/ kg体重,连用42 d),锌+他莫昔芬联合(Zn+Tam)组家兔口服锌和他莫昔芬等剂量。目的:研究选择性雌激素受体调节剂他莫昔芬对心肌的影响。结果锌处理组心脏组织病理检查未见明显组织学异常,他莫昔芬组心脏组织出现大量坏死组织,损伤部位有大量炎性细胞浸润,联合用药组病变部位炎症反应活跃,包括血管充血、水肿形成,炎性细胞聚集,尤其是巨噬细胞和肌细胞空泡化。因此,研究发现心脏细胞内活性氧(ROS)的过度产生以及ROS生成系统与抗氧化系统之间的不平衡可能导致对组织和细胞的潜在危害。
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Oxidative stress induced cardiomyocytes injury by Tamoxifen and abrogates by zinc supplement in adult female rabbits
Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and  Drug Administration in 1977. However, TAM therapy is accompanied with cardiomyocytes apoptosis. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM apoptosis. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced cardiomyocytes injury in adult female rabbits. Rabbits were received zinc orally (0.3 mg/ kg body weight / day for 42 days) in zinc group, Tamoxifen group were received orally (0.25 mg/ kg body weight for 42 days), and combination (Zn+Tam) group were received equal dose from zinc and tamoxifen. To study the effect of the tamoxifen (selective estrogen receptor modulator) on the cardiac muscle. Results showed of histopathological study of heart taken from zinc treated group not showed any important abnormalities in histological appearance, tamoxifen group in heart tissue showed a massive necrotic tissue  and a huge inflammatory cell infiltration to damaged area and combination group lesion showed active inflammatory process which included blood vessels congestion, edema formation,  inflammatory cell aggregation especially macrophage and Myocyte vacuolization. As a consequence, the finding of the research Tam induction over production of reactive oxygen species (ROS) within cardiac cell and the imbalance between the ROS generating system and the antioxidant system can lead to a potentially harmful to tissues and cells.
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