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Evidence for genistein mediated cytotoxicity and apoptosis in rat brain.

机译:金雀异黄素介导的大鼠脑细胞毒性和细胞凋亡的证据。

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The effects of chronic treatment with high doses of genistein, a major isoflavone of soybeans and soy-based products, have yet to be determined and what is known remains controversial. The present study was undertaken to investigate the cytotoxic effects of chronic ingestion of genistein on rat brain in vivo and the observations were compared with results from in vitro studies with primary cultures of cortical neurons. Sprague-Dawley rats were given 2 or 20 mg/day genistein (p.o.) for four weeks. The high dose of genistein (20 mg/day) significantly increased lactate dehydrogenase (LDH) in rat brain tissue homogenates, whereas the low dose of genistein (2 mg/day) decreased LDH. In addition, DNA fragmentation was detected in homogenates of brain tissue from rats receiving either dose of genistein. These results are consistent with those of in vitro studies indicating that high concentrations of genistein caused cytotoxicity and DNA ladder formation in primary cultures of cortical neurons. Genistein decreased the expression of the 32 kDa caspase-3 precursor and increased the levels of cleaved caspase-3 (18 kDa) in both rat brain tissue homogenates and in primary cultures of cortical neurons. Furthermore, expression of poly (ADP-ribose) polymerase (PARP) was also decreased in both experimental systems. These results suggest that chronic administration of genistein at high doses may induce cytotoxicity and apoptosis in the rat brain.
机译:高剂量染料木黄酮(一种大豆和大豆制品的主要异黄酮)的长期治疗效果尚未确定,已知的方法仍存在争议。进行本研究以研究体内染料木黄酮长期摄入对大鼠脑的细胞毒性作用,并将观察结果与皮层神经元原代培养物的体外研究结果进行比较。给予Sprague-Dawley大鼠2或20毫克/天的染料木黄酮(口服),持续4周。高剂量的染料木黄酮(20 mg /天)可显着增加大鼠脑组织匀浆中的乳酸脱氢酶(LDH),而低剂量的染料木黄酮(2 mg / day)可降低LDH。另外,在接受任一剂量染料木黄酮的大鼠的脑组织匀浆中检测到DNA片段化。这些结果与体外研究的结果一致,后者表明高浓度的染料木黄酮会在皮层神经元的原代培养物中引起细胞毒性和DNA阶梯形成。金雀异黄素降低了大鼠脑组织匀浆和皮层神经元原代培养物中32 kDa caspase-3前体的表达,并增加了裂解的caspase-3(18 kDa)水平。此外,在两个实验系统中,聚(ADP-核糖)聚合酶(PARP)的表达也降低了。这些结果表明,大剂量染料木黄酮的长期给药可能诱导大鼠脑细胞毒性和细胞凋亡。

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