Department of Public Health Sciences, Penn State Hershey Cancer Institute, Penn State University College of Medicine, 500 University Drive, P.O. Box 850, Hershey, Pennsylvania 17033, USA.
Exp Gerontol. 2012 Mar;47(3):223-8. doi: 10.1016/j.exger.2011.11.015. Epub 2011 Dec 24.
Aging represents a major risk factor for prostate cancer; however, mechanisms responsible for this relationship remain unclear. Preclinical and some clinical investigations support the protective role of selenium against prostate cancer possibly through the reduction of oxidative stress. While increased levels of oxidative stress together with decreases in selenium and the major cellular antioxidant glutathione (GSH) are common in tissues of old animals, there is little data available on these parameters in the prostate. In the present study we have compared the levels of selenium, GSH and protein-bound GSH (GSSP) in blood and prostate tissues in young (4-month), mature (12-month), old (18 month), and very old (24 month) male F344 rats. Each prostate lobe (dorsolateral, DL; anterior, AL; ventral, VL) was analyzed separately based upon their differing potential for prostate cancer development. At all ages, selenium levels were lowest in DL<VL<AL. After 12 mo, an 85% reduction in selenium in the DL was observed (P<0.05), while levels in other lobes were unchanged. In animals of all ages, levels of GSH were lowest in the VL<DL=AL and no significant changes were observed in GSH levels by 18 mo. However, GSSP, a marker of oxidative stress, was increased 90% after 18 mo in the DL only (P<0.01). These findings of age-related changes in GSSP and selenium in the DL prostate are consistent with the sensitivity of this lobe to carcinogenesis and, thus, may be playing a mechanistic role.
衰老代表着前列腺癌的一个主要危险因素;然而,导致这种关系的机制仍不清楚。临床前和一些临床研究支持硒对前列腺癌的保护作用,这可能是通过降低氧化应激来实现的。虽然在老年动物的组织中,氧化应激水平的增加以及硒和主要细胞抗氧化剂谷胱甘肽 (GSH) 的减少很常见,但关于前列腺中这些参数的数据很少。在本研究中,我们比较了年轻(4 个月)、成熟(12 个月)、老年(18 个月)和非常老(24 个月)雄性 F344 大鼠血液和前列腺组织中的硒、GSH 和蛋白结合 GSH(GSSP)水平。根据不同的前列腺癌发生潜力,分别分析每个前列腺叶(背外侧、DL;前侧、AL;腹侧、VL)。在所有年龄段,DL<VL<AL 中的硒水平最低。12 个月后,DL 中的硒减少了 85%(P<0.05),而其他叶中的硒水平没有变化。在所有年龄段的动物中,GSH 水平在 VL<DL=AL 中最低,到 18 个月时 GSH 水平没有明显变化。然而,只有在 DL 中,氧化应激的标志物 GSSP 在 18 个月后增加了 90%(P<0.01)。这些与年龄相关的 GSSP 和硒在 DL 前列腺中的变化发现与该叶对致癌作用的敏感性一致,因此可能起着机械作用。