Bruniera Felipe R, Ferreira Felipe M, Savioli Luiz R M, Bacci Marcelo R, Feder David, Pereira Edimar C, Pedreira Mavilde L G, Peterlini Maria A S, Perazzo Fábio F, Azzalis Ligia A, Rosa Paulo C P, Junqueira Virginia B C, Sato Monica A, Fonseca Fernando L A
Disciplina de Farmacologia, Departamento de Morfologia, Faculdade de Medicina do ABC, Santo André, SP, Brasil.
Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP, Brasil.
An Acad Bras Cienc. 2014 Dec;86(4):1963-72. doi: 10.1590/0001-3765201420140204.
Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it is not considered a first-choice drug because of its adverse effects. It is believed that oxidative stress is the primary mechanism of endothelial injury and the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity. Moreover, dose recommendations, dilution, rates and types of infusion are still controversial. The aim of this study was to determine the effect of different VCM dilutions in endothelial, liver and kidney injuries by biochemical parameters and histopathological analysis. Wistar rats were randomly divided into six groups and subjected to femoral vein cannulation for drug administration. Control groups received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT, urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This study showed alterations in ALT which featured hepatotoxicity. However, drug dilutions were not able to show changes in other biochemical parameters. In contrast, kidney and endothelium pathological changes were observed. More studies are needed to characterize VCM induced kidney and endothelium toxicity and biochemical markers able to show such morphological modifications.
万古霉素（VCM）可用于对抗革兰氏阳性菌感染，但由于其不良反应，它并非首选药物。据信，氧化应激是内皮损伤及随之而来的VCM毒性的主要机制，这种毒性表现从静脉炎到肾毒性不等。此外，剂量推荐、稀释方法、输注速率和类型仍存在争议。本研究的目的是通过生化参数和组织病理学分析来确定不同VCM稀释度对内皮、肝脏和肾脏损伤的影响。将Wistar大鼠随机分为六组，并进行股静脉插管以便给药。对照组接受0.9毫升生理盐水，其他组接受浓度为5.0和10.0毫克/毫升的VCM（10毫克/千克/天），持续3天和7天。分析了同型半胱氨酸、超敏C反应蛋白、谷草转氨酶、谷丙转氨酶、γ-谷氨酰转移酶、尿素、肌酐、番茄红素、α-生育酚、β-胡萝卜素和视黄醇。收集了肾脏、肝脏和股静脉插管片段。本研究显示谷丙转氨酶发生改变，呈现肝毒性特征。然而，药物稀释未能显示其他生化参数的变化。相反，观察到了肾脏和内皮的病理变化。需要更多研究来明确VCM诱导的肾脏和内皮毒性以及能够显示这种形态学改变的生化标志物。
