4-苯基四氢喹啉通过抑制自噬对四氯化碳诱导的大鼠肝中毒的保肝作用

IF 4.3 2区 生物学 Q1 BIOLOGY
Mohamed Hussein Abdelgalil, Reem H Elhammamy, Hanan M Ragab, Eman Sheta, Ahmed Wahid
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引用次数: 0

摘要

背景:肝脏是人体内的代谢枢纽,在解毒、营养代谢和激素调节等各种基本功能中发挥着至关重要的作用。因此,保护肝脏免受内源性和外源性损伤已成为医学研究的首要重点。因此,多种 4-苯基四氢喹啉的潜在保肝特性激发了我们深入研究四种专门设计合成的衍生物对四氯化碳(CCl4)诱导的大鼠肝损伤的影响:将体重为 140 ± 18 克的 77 只 Wistar 白化雄性大鼠分为 11 组,研究 4-苯基四氢喹啉的毒性概况和保肝潜力。使用四氯化碳(1 毫升/千克体重,1:1 v/v 与玉米油的混合物,静脉注射)进行体内肝毒性模型试验,每 72 小时一次,连续 14 天。同时,每 24 小时用我们新合成的化合物(每种剂量为 25 毫克/千克体重,悬浮于 0.5% CMC 中,口服)治疗大鼠,可有效降低转氨酶,保护肝组织完整性,减轻氧化应激和炎症反应。此外,肝组织病理学检查显示,肝纤维化显著减少,α-SMA 的免疫组化分析进一步证实了这一点。此外,利用实时 PCR 监测了凋亡基因 BAX 和 BCL2 的表达,结果显示肝脏凋亡明显减少。进一步的研究发现,这些化合物能够显著降低自噬相关蛋白 Beclin-1 和 LC3B 的表达,从而抑制自噬。最后,我们的计算机辅助模拟对接证实了所获得的实验活性:我们的研究结果表明,4-苯基四氢喹啉衍生物对 CCl4 诱导的大鼠肝损伤和肝纤维化具有保肝作用。潜在的作用机制可能是由于抑制了肝细胞的自噬作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The hepatoprotective effect of 4-phenyltetrahydroquinolines on carbon tetrachloride induced hepatotoxicity in rats through autophagy inhibition.

Background: The liver serves as a metabolic hub within the human body, playing a crucial role in various essential functions, such as detoxification, nutrient metabolism, and hormone regulation. Therefore, protecting the liver against endogenous and exogenous insults has become a primary focus in medical research. Consequently, the potential hepatoprotective properties of multiple 4-phenyltetrahydroquinolines inspired us to thoroughly study the influence of four specially designed and synthesized derivatives on carbon tetrachloride (CCl4)-induced liver injury in rats.

Methods and results: Seventy-seven Wistar albino male rats weighing 140 ± 18 g were divided into eleven groups to investigate both the toxicity profile and the hepatoprotective potential of 4-phenyltetrahydroquinolines. An in-vivo hepatotoxicity model was conducted using CCl4 (1 ml/kg body weight, a 1:1 v/v mixture with corn oil, i.p.) every 72 h for 14 days. The concurrent treatment of rats with our newly synthesized compounds (each at a dose of 25 mg/kg body weight, suspended in 0.5% CMC, p.o.) every 24 h effectively lowered transaminases, preserved liver tissue integrity, and mitigated oxidative stress and inflammation. Moreover, the histopathological examination of liver tissues revealed a significant reduction in liver fibrosis, which was further supported by the immunohistochemical analysis of α-SMA. Additionally, the expression of the apoptotic genes BAX and BCL2 was monitored using real-time PCR, which showed a significant decrease in liver apoptosis. Further investigations unveiled the ability of the compounds to significantly decrease the expression of autophagy-related proteins, Beclin-1 and LC3B, consequently inhibiting autophagy. Finally, our computer-assisted simulation dockingonfirmed the obtained experimental activities.

Conclusion: Our findings suggest that derivatives of 4-phenyltetrahydroquinoline demonstrate hepatoprotective properties in CCl4-induced liver damage and fibrosis in rats. The potential mechanism of action may be due to the inhibition of autophagy in liver cells.

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来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
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