Resveratrol treatment ameliorates hepatic damage via the TGF-β/SMAD signaling pathway in a phenobarbital/CCl4-induced hepatic fibrosis model.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/IJBMS.2024.75737.16398
Merve Aykaç, Eda Balkan, Semin Gedi Kli, Nurinnisa Öztürk
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Abstract

Objectives: Liver fibrosis is a wound healing response characterized by excessive accumulation of extracellular matrix proteins. This study aimed to investigate the effects of resveratrol treatment on the TGF-β/SMAD signaling pathway and related biochemical parameters, apoptosis, and liver regeneration phenobarbital-CCl4 induced hepatic fibrosis rat model.

Materials and methods: This model was created through phenobarbital and CCl4 (0.2-0.35 ml/kg). Resveratrol (1 mg/kg/day) was administered to the fibrosis and control groups. Immunohistochemical staining was performed to evaluate αSMA, TGF-β1, and PCNA in liver tissue. The TUNEL method and Masson's Trichome staining were used to determine apoptosis and collagen accumulation. AST, ALP, ALT, total protein, and total bilirubin levels were measured to determine biochemical status. SMAD2, SMAD3, SMAD4, and SMAD7 expression levels were measured to determine TGF-β1 related hepatic fibrosis.

Results: The SMAD2, SMAD3, and SMAD4 mRNA expression levels were increased and the SMAD7 mRNA expression level was decreased in the fibrosis control group. The SMAD7 mRNA expression level was higher in the phenobarbital-CCl4 induced resveratrol treated group. Increased biochemical parameters indicating hepatic damage, increased number of apoptotic cells, and collagen accumulation surrounding the central vein were observed in the fibrosis group compared with the other groups. It was concluded that administration of resveratrol ameliorates the adverse effects of hepatic fibrosis by regulating biochemical parameters, controlling TGF-β1/SMAD signaling, enhancing tissue regeneration, and reducing apoptosis in liver cells.

Conclusion: Resveratrol can be a beneficial option for the prevention of liver damage in a phenobarbital-CCl4 induced hepatic fibrosis.

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在苯巴比妥/CCl4诱导的肝纤维化模型中,白藜芦醇通过TGF-β/SMAD信号通路改善肝损伤。
目的:肝纤维化是一种以细胞外基质蛋白过度积累为特征的伤口愈合反应。本研究旨在探讨白藜芦醇治疗对 TGF-β/SMAD 信号通路及相关生化指标、细胞凋亡和肝再生的影响:该模型通过苯巴比妥和CCl4(0.2-0.35 ml/kg)建立。肝纤维化组和对照组分别服用白藜芦醇(1 毫克/千克/天)。对肝组织中的αSMA、TGF-β1和PCNA进行免疫组化染色。采用 TUNEL 法和 Masson's Trichome 染色法确定细胞凋亡和胶原堆积情况。测定 AST、ALP、ALT、总蛋白和总胆红素水平以确定生化状态。测定SMAD2、SMAD3、SMAD4和SMAD7的表达水平,以确定与TGF-β1相关的肝纤维化:结果:肝纤维化对照组中,SMAD2、SMAD3和SMAD4 mRNA表达水平升高,SMAD7 mRNA表达水平降低。苯巴比妥-氯化萘诱导的白藜芦醇治疗组的 SMAD7 mRNA 表达水平较高。与其他组相比,肝纤维化组的生化指标增加,表明肝损伤、凋亡细胞数量增加,中心静脉周围胶原堆积。结论:白藜芦醇可通过调节生化指标、控制 TGF-β1/SMAD 信号转导、促进组织再生和减少肝细胞凋亡来改善肝纤维化的不良影响:白藜芦醇是预防苯巴比妥-氯化萘诱导的肝纤维化中肝脏损伤的有益选择。
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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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