School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei 230009, China.
Food Chem Toxicol. 2013 May;55:172-81. doi: 10.1016/j.fct.2013.01.003. Epub 2013 Jan 16.
The purpose of this study was to investigate genistein's influence on the relationship between the activation of uridine diphosphate glucuronosyltransferase (UGTs) and the protection against acetaminophen-induced liver toxicity. Animal experimental results revealed that genistein (50, 100 or 200mg/BWkg) significantly ameliorated the biomarkers alanine aminotransferase, alanine aminotransferase, lactate dehydrogenase and malondialdehyde, as indicators of acute liver damage caused by APAP (200mg/BWkg). The level of GSH declined sharply after treatment with APAP within 1h in both the liver and blood with and without genistein. However, after 16h, the levels approached or returned to the original level. Genistein may accelerate and promote APAP glucuronidation as the results showed that APAP-glucuronide increased by 18.44%, 46.79%, and 66.49% for 4h of treatment with genistein dosages of 50, 100 or 200mg/BWkg, respectively, compared with the APAP-only treatment. The activation of UGTs and glutathione peroxidase and the inhibition of CYP2E1 by genistein were observed, and UGTs mRNA expression level with genistein was measured. These findings suggest that genistein can prevent and protect against APAP-induced liver toxicity due to the inhibition of APAP biotransformation and the resistance to oxidative stress via the modulation of the activities of metabolism and the antioxidant enzyme.
本研究旨在探讨染料木黄酮对尿苷二磷酸葡萄糖醛酸转移酶（UGTs）激活与对乙酰氨基酚（APAP）诱导的肝毒性保护之间关系的影响。动物实验结果表明，染料木黄酮（50、100 或 200mg/kg）可显著改善丙氨酸氨基转移酶、天冬氨酸氨基转移酶、乳酸脱氢酶和丙二醛等生物标志物，这些标志物是 APAP（200mg/kg）引起的急性肝损伤的指标。APAP 处理后 1h，无论是否给予染料木黄酮，肝和血液中的 GSH 水平均急剧下降。然而，16h 后，水平接近或恢复到原始水平。染料木黄酮可能会加速和促进 APAP 的葡萄糖醛酸化，因为结果表明，用 50、100 或 200mg/kg 染料木黄酮处理 4h 后，APAP-葡萄糖醛酸苷分别增加了 18.44%、46.79%和 66.49%，与仅用 APAP 处理相比。观察到 UGTs 和谷胱甘肽过氧化物酶的激活以及 CYP2E1 被染料木黄酮抑制，并用染料木黄酮测量了 UGTs mRNA 的表达水平。这些发现表明，染料木黄酮可以通过抑制 APAP 生物转化和通过调节代谢和抗氧化酶的活性来抵抗氧化应激，从而预防和保护 APAP 诱导的肝毒性。
