乙酰唑胺可抑制二乙亚硝胺诱导的 Wistar 白化大鼠肝细胞癌的发展。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yomna M Tamim, Mohamed L Soliman, Moataz M Sayed, Muhammad S Abdul-Rasheed, Ahmed A Nagy, Ahmed M Abdellah, Ahmed H Osman, Amel F M Ismail
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引用次数: 0

摘要

肝细胞癌(HCC)仍然是全球最常见的肝癌类型。二乙基亚硝胺(DEN)诱导的 HCC 是一种广泛用于实验动物的肝癌模型。乙酰唑胺(AZA)是一种碳酸酐酶抑制剂。本研究旨在评估AZA对DEN诱导的HCC的治疗机制。将 30 只雄性 Wistar 白化大鼠平均分为三组。第一组(C):对照组;第二组(HCC):DEN 诱导的 HCC;第三组(C):DEN 诱导的 HCC:第三组(HCC/AZA):AZA治疗的HCC。肝酶活性升高、α-胎儿蛋白(AFP)水平升高以及明显的肝脏结构变化证实了DEN诱导的HCC。另一方面,经 AZA 处理的 HCC 组血清肝酶活性和 AFP 水平下降,肝脏结构也得到调节。此外,它还能降低 p-p38 MAPK/p-JNK1/JNK2/p-C-Jun/p-NF-κB p65 蛋白的表达。此外,它还通过控制 p-AMPK/p-mTOR1/LC3 I/II 蛋白的表达来改善自噬。此外,它还下调了碳酸酐酶-IX(CAIX)和己糖激酶-II(HKII)的相对基因表达。经 AZA 处理的 HCC 肝组织的组织病理学检查证实了这些发现。结论AZA 通过调节肝脏生物标志物、抗氧化状态、炎症标志物和自噬,在改善 CAIX 和 HKII 基因表达的介导下,为改善实验诱导的 HCC 提供了一个新的维度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Acetazolamide suppresses the progression of hepatocellular carcinoma induced by diethylnitrosamine in Wistar albino rats.

Hepatocellular carcinoma (HCC) continues to be the most prevalent type of liver cancer worldwide. Diethylnitrosamine (DEN)-induced HCC is an extensively used hepatic cancer model in experimental animals. Acetazolamide (AZA) is a carbonic anhydrase enzyme inhibitor. This study aimed to assess the therapeutic mechanism of AZA against DEN-induced HCC. Thirty male Wistar albino rats were divided equally into three groups. Group I (C): control group, Group II (HCC): DEN-induced HCC, and Group III (HCC/AZA): AZA-treated HCC. Verification of the HCC induced by DEN was confirmed by elevated liver enzymes' activities, and increased α-fetoprotein (AFP) levels, as well as distinct liver architecture changes. On the other hand, the AZA-treated HCC group experienced decreases in the activities of serum liver enzymes and AFP levels, as well as, regulated liver architecture. Additionally, it downregulated p-p38 MAPK/p-JNK1/JNK2/p-C-Jun/p-NF-κB p65 protein expressions. Moreover, it ameliorated autophagy by controlling the expression of the p-AMPK/p-mTOR1/LC3 I/II proteins. Furthermore, it downregulated the relative gene expressions of carbonic anhydrase-IX (CAIX) and hexokinase-II (HKII). Histopathological examination of AZA-treated HCC liver tissues supported these findings. Conclusion: AZA provides a new dimension in ameliorating experimentally induced HCC through regulation of hepatic biomarkers, antioxidant status, inflammatory markers, and autophagy, mediated by amelioration of CAIX and HKII gene expressions.

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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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