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Chemo-preventive effect of crocin against experimentally-induced hepatocarcinogenesis via regulation of apoptotic and Nrf2 signaling pathways.
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-09-14 , DOI: 10.1016/j.etap.2020.103494
Nehal M Elsherbiny 1 , Nada H Eisa 2 , Mohamed El-Sherbiny 3 , Eman Said 4
Affiliation  

The results of the current study investigated the chemo-preventive effect of crocin against hepatocarcinogenesis in rats with particular focus on the evaluation of the modulatory impact of crocin on apoptotic and nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathways. Thioacetamide (TAA) (200 mg/kg, I.P.) was used for experimental induction of hepatocarcinogenesis in rats. Crocin administration significantly attenuated TAA-induced cancerous lesions with concomitant attenuation of impaired liver functions. This was associated with significant enhancement in hepatic Nrf2 and heme oxygenase-1 (HO-1) expression with parallel suppression in Keap-1 expression. Inline, crocin induced a significant improvement in hepatic oxidative status with enhanced antioxidant batteries. Crocin administration significantly suppressed the hepatic content of c-Jun N-terminal kinase (c-JNK) with significant upregulation in TNF-related apoptosis-inducing ligand (TRAIL) and caspase-8 protein expression as well as p53 gene expression; biomarkers of apoptosis. Moreover, hepatic expression of the apoptotic BAX significantly increased and the anti-apoptotic Bcl-2 significantly decreased in the liver specimen; biomarkers of intrinsic apoptosis. In conclusion; crocin attenuates experimentally induced hepato-carcinogenesis via modulation of oxidative/apoptotic signaling. Namely, crocin induced hepatic expression of Nrf2 with downstream modulation of endogenous HO-1 and Keap-1 signaling with modulation of various key players of apoptosis including; c-JNK, p53, TRAIL, caspase-8, BAX, and Bcl-2.



中文翻译:

番红花通过凋亡和Nrf2信号通路的调节对实验诱导的肝癌发生的化学预防作用。

本研究的结果调查了番红花对大鼠肝癌发生的化学预防作用,特别侧重于评估番红花对凋亡和核因子红系2相关因子2(Nrf2)信号通路的调节作用。硫代乙酰胺(TAA)(200 mg / kg,IP)用于实验诱导大鼠肝癌的发生。服用番红花可显着减轻TAA诱导的癌性病变,并同时削弱受损的肝功能。这与肝Nrf2和血红素加氧酶-1(HO-1)表达的显着增强相关,而Keap-1表达受到平行抑制。在线显示,用增强的抗氧化剂电池,番红花可以显着改善肝脏的氧化状态。番红花给药可显着抑制c-Jun N末端激酶(c-JNK)的肝内含量,并显着上调TNF相关凋亡诱导配体(TRAIL)和caspase-8蛋白表达以及p53基因表达。凋亡的生物标志物。此外,肝脏标本中凋亡BAX的肝表达显着增加,抗凋亡Bcl-2显着降低。内在凋亡的生物标志物。结论; 番红花通过调节氧化/凋亡信号减弱了实验诱导的肝癌发生。即,番红花素通过内源性HO-1的下游调节和Keap-1信号转导以及多种凋亡关键因子的调节来诱导Nrf2的肝表达。c-JNK,p53,TRAIL,caspase-8,BAX和Bcl-2。

更新日期:2020-09-24
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