姜黄素恢复丙硫氧嘧啶（PTU）诱导的甲状腺功能减退雄性大鼠肝脏的表观遗传变化：对 DNMTs、MBDs、GADD45a、C/EBP-β 和 PCNA 的研究。
Curcumin restores hepatic epigenetic changes in propylthiouracil(PTU)Induced hypothyroid male rats: A study on DNMTs, MBDs, GADD45a, C/EBP-β and PCNA.
机构信息
P.G. Department of Biotechnology, Utkal University, Bhubaneswar, 751004, Odisha, India.
P.G. Department of Biotechnology, Utkal University, Bhubaneswar, 751004, Odisha, India.
出版信息
Food Chem Toxicol. 2019 Jan;123:169-180. doi: 10.1016/j.fct.2018.10.050. Epub 2018 Oct 24.
6-n-propyl-2-thiouracil (PTU), a thioamide drug, is used as an effective anti-thyroid agent to treat hyperthyroidism and Graves' disease. However, acute liver oxidative damage is an important side effect of the drug. In the present study, we report that PTU administration to rat induces hepatic epigenetic changes by upregulating expression of DNMT1, DNMT3a, DNMT3b, MBD4, MeCP2, p53 and Gadd45a and down-regulation of PCNA and C/EBP-β. This is accompanied by decrease in the cell population and augmentation of cellular lipid peroxidation, an index of oxidative stress, in liver. On the other hand, co-administration of curcumin, a polyphenol extract from the rhizome of Curcuma longa L, along with PTU ameliorates PTU- induced oxidative stress and epigenetic parameters except for the expression of MBD4. Also, co-administration of curcumin with PTU resulted in restoration of hepatic cell population and histoarchitecture. The protective effect of curcumin to PTU-induced hepatotoxicity is attributed to its antioxidative properties.
6-正丙基-2-硫代尿嘧啶（PTU），一种硫代酰胺药物，被用作治疗甲状腺功能亢进和格雷夫斯病的有效抗甲状腺药物。然而，急性肝氧化损伤是该药物的一个重要副作用。在本研究中，我们报告称，PTU 给药会通过上调 DNMT1、DNMT3a、DNMT3b、MBD4、MeCP2、p53 和 Gadd45a 的表达以及下调 PCNA 和 C/EBP-β 的表达，诱导大鼠肝的表观遗传改变。这伴随着肝中细胞群体减少和细胞脂质过氧化增加，这是氧化应激的一个指标。另一方面，姜黄素（姜黄根茎中的多酚提取物）与 PTU 联合给药可改善 PTU 诱导的氧化应激和表观遗传参数，除 MBD4 的表达外。此外，PTU 与姜黄素联合给药可恢复肝细胞群体和组织形态。姜黄素对 PTU 诱导的肝毒性的保护作用归因于其抗氧化特性。
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