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白藜芦醇对α-鹅膏蕈碱诱导的大鼠肝毒性的保护作用。

Hepatoprotective effects of resveratrol on α-amanitin-induced liver toxicity in rats.

机构信息

Vocational School of Health Services, Atatürk University, Erzurum, Türkiye; Pharmaceutical Research and Development, Graduate School of Natural and Applied Sciences, Atatürk University, Erzurum, Türkiye.

Erzincan Binali Yıldırım University, Faculty of Medicine, Department of Physiology, Erzincan, Türkiye.

出版信息

Toxicon. 2024 Aug 28;247:107855. doi: 10.1016/j.toxicon.2024.107855. Epub 2024 Jul 10.

Abstract

OBJECTIVE

The hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function.

METHODS

Thirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT).

RESULTS

α-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements.

CONCLUSION

Resveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.

摘要

目的

研究白藜芦醇(resveratrol)对α-鹅膏蕈碱(α-AMA)诱导的肝毒性的保护作用,重点关注氧化应激、炎症、凋亡和肝功能。

方法

32 只雄性 Sprague-Dawley 大鼠分为四组(每组 8 只):对照组、白藜芦醇组、α-AMA 组和白藜芦醇+α-AMA 组。白藜芦醇组连续 7 天口服 20mg/kg 白藜芦醇。α-AMA 组第 8 天腹腔内注射 3mg/kg α-AMA。白藜芦醇+α-AMA 组第 7 天连续口服 20mg/kg 白藜芦醇,第 8 天腹腔内注射 3mg/kg α-AMA。α-amanitin 给药后 48 小时采集肝组织和血样,进行组织病理学、免疫组织化学(NFkB、LC3B)和生化分析(GSH、MDA、CAT、GPx、MPO、NOS、AST、ALT)。

结果

α-AMA 显著增加 AST 和 ALT 水平、氧化应激标志物(MDA)和炎症标志物(MPO),同时降低抗氧化水平(GSH、CAT、GPx)和 NOS 浓度(所有参数 P<0.001)。组织病理学分析显示肝损伤严重,NFkB 和 LC3B 表达增加。白藜芦醇治疗显著降低 AST 和 ALT 水平(两个参数均 P<0.01),降低 MDA 和 MPO 水平,增加 NOS 浓度、GSH、CAT 和 GPx 水平(所有参数均 P<0.05)。白藜芦醇+α-AMA 组 NFkB 和 LC3B 表达减少,组织病理学改善。

结论

白藜芦醇通过减少氧化应激、炎症和凋亡,改善肝功能,对 α-AMA 诱导的肝毒性具有显著的保护作用。这些发现表明,白藜芦醇可能是治疗 α-AMA 等强效肝毒素引起的肝损伤的潜在治疗药物。

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