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白藜芦醇对 BALB/c 小鼠α-鹅膏蕈碱肾毒性的影响。

Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice.

机构信息

Division of Clinical Pharmacology, Department of Medical Pharmacology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

Department of Emergency Medicine, School of Medicine, Karadeniz Technical University, Trabzon, Turkey.

出版信息

Hum Exp Toxicol. 2020 Mar;39(3):328-337. doi: 10.1177/0960327119888271. Epub 2019 Nov 14.

Abstract

Alpha-amanitin (α-AMA), the primary toxin of , is known to cause nephrotoxicity and hepatotoxicity. Resveratrol is an antioxidant that has shown efficacy in many nephrotoxicity models. The aim of this study was to investigate the effects of resveratrol against the early and late stages of α-AMA-induced nephrotoxicity, compared to those of silibinin, a well-known antidote for poisoning by α-AMA-containing mushrooms. Mice kidney tissues were obtained from five groups: (1) α-AMA + NS (simultaneous administration of α-AMA and normal saline), (2) α-AMA + SR (simultaneous administration of α-AMA and resveratrol), (3) α-AMA + 12R (resveratrol administration 12 h after α-AMA administration), (4) α-AMA + 24R (resveratrol administration 24 h after α-AMA administration), and (5) α-AMA + Sil (simultaneous administration of α-AMA and silibinin). Histomorphological and biochemical analyses were performed to evaluate kidney damage and oxidant-antioxidant status in the kidney. Scores of renal histomorphological damage decreased significantly in the early resveratrol treatment groups (α-AMA + SR and α-AMA + 12R), compared to those in the α-AMA + NS group ( < 0.05). Catalase levels increased significantly in the α-AMA + SR group, compared to those in the α-AMA + NS group ( < 0.001). Early resveratrol administration within 12 h after α-AMA ingestion may reverse the effects of α-AMA-induced nephrotoxicity, partly through its antioxidant action, thereby suggesting its potential as a treatment for poisoning by α-AMA-containing mushrooms.

摘要

α-鹅膏蕈碱(α-AMA)是导致肾毒性和肝毒性的主要毒素。白藜芦醇是一种抗氧化剂,在许多肾毒性模型中都显示出了疗效。本研究旨在探讨白藜芦醇对α-AMA 诱导的早期和晚期肾毒性的作用,并与含 α-AMA 蘑菇中毒的已知解毒剂水飞蓟素进行比较。从五组小鼠肾脏组织中获得:(1)α-AMA + NS(同时给予α-AMA 和生理盐水),(2)α-AMA + SR(同时给予α-AMA 和白藜芦醇),(3)α-AMA + 12R(α-AMA 给药后 12 小时给予白藜芦醇),(4)α-AMA + 24R(α-AMA 给药后 24 小时给予白藜芦醇),和(5)α-AMA + Sil(同时给予α-AMA 和水飞蓟素)。进行组织形态学和生化分析以评估肾脏损伤和肾脏中的氧化应激状态。与 α-AMA + NS 组相比,早期白藜芦醇治疗组(α-AMA + SR 和 α-AMA + 12R)的肾脏组织形态学损伤评分显着降低(<0.05)。与 α-AMA + NS 组相比,α-AMA + SR 组的过氧化氢酶水平显着升高(<0.001)。在摄入α-AMA 后 12 小时内早期给予白藜芦醇可能会逆转α-AMA 诱导的肾毒性的作用,部分通过其抗氧化作用,从而表明其可能作为含α-AMA 蘑菇中毒的治疗方法。

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