Expression data from livers of rats with and without rotenone treatment. Rattus norvegicus

We investigated an subacute study in male Wistar rats, treated daily with 400 ppm rotenone for 1, 3, or 14 consecutive days, followed by necropsy 24h after the last application. Rotenone is a strong mitochondrial respiratory chain complex I inhibitor. Inhibitors of complex I are suggested to exert anti-tumor activity of those tumors relying on oxidative metabolism and are therefore of interest in oncology research. Nevertheless, the safety profile of these inhibitors needs to be rigorously assessed. Rotenone has shown anti-carcinogenic activity in several studies. In this context we used rotenone in our study as tool compound with the aim to identify suitable biomarker candidates and enhance mechanistic insights into the biologic and cellular effects of complex I inhibitors at the organ level after in vivo treatment. Various parameters, including hematology, clinical chemistry and histopathology, major blood cell population phenotyping using FACS and enzymatic activity assays were measured and/or evaluated. Moreover gene expression profiles were determined to investigate pathways and functions affected by rotenone at the molecular level. As organs, liver, heart and brain stem were chosen due to the high metabolic activity, the high energy demand and due to the known neurotoxic effect of rotenone, respectively. The strongest rotenone-induced effects on gene expression were observed in the liver (1444 deregulated genes) compared to heart (650 deregulated genes) and brain stem (52 deregulated genes). These findings, together with the histopathological results, show that liver is a target organ of rotenone. Overall design: Male RccHan Wistar rats at the age of 7-8 weeks were randomly assigned to the vehicle or treatment group (n=5). Then 0 or 400 ppm rotenone (Sigma Aldrich, Steinheim, Germany) was administered in the diet for 1, 3 or 14 consecutive days, followed by necropsy. Blood was collected for clinical chemistry and hematology and several organs were removed, weighted, aliquoted, fixed in formalin for histopathological examinations or flash frozen in liquid nitrogen and stored at −80 °C for RNA isolation.

本研究开展了一项亚急性动物实验，以雄性Wistar大鼠为研究对象，每日给予400 ppm鱼藤酮，连续给药1、3或14天，末次给药24小时后实施剖检。鱼藤酮是一种强效的线粒体呼吸链复合体I（Complex I）抑制剂。复合体I抑制剂被认为可对依赖氧化代谢的肿瘤发挥抗肿瘤活性，因此在肿瘤学研究中具有重要研究价值。然而，此类抑制剂的安全性仍需严格评估。已有多项研究表明鱼藤酮具有抗癌活性。基于此，本研究将鱼藤酮作为工具化合物，旨在筛选合适的候选生物标志物，并深入解析体内给药后复合体I抑制剂在器官层面的生物学与细胞效应机制。本研究检测并/或评估了多项参数，包括血液学、临床生化、组织病理学、采用流式细胞术（FACS）的主要血细胞群表型分析，以及酶活性检测。此外，通过检测基因表达谱，以解析鱼藤酮在分子层面影响的通路与生物学功能。本研究选取肝脏、心脏与脑干作为研究对象，分别基于其高代谢活性、高能量需求，以及鱼藤酮已知的神经毒性效应。与心脏（650个差异表达基因）和脑干（52个差异表达基因）相比，鱼藤酮对肝脏基因表达的调控作用最为显著（1444个差异表达基因）。结合组织病理学结果，上述发现表明肝脏是鱼藤酮的靶器官。

实验设计概述：选取7-8周龄的雄性RccHan Wistar大鼠，随机分为溶剂对照组与给药组（每组n=5）。随后通过日粮连续1、3或14天给予0（溶剂对照）或400 ppm鱼藤酮（购自德国施泰因海姆市西格玛奥德里奇（Sigma Aldrich）公司），末次给药24小时后实施剖检。采集血液用于临床生化与血液学检测；摘取多个脏器，称重后分装，一部分用福尔马林固定以用于组织病理学检查，另一部分经液氮快速冷冻后于-80℃保存，用于RNA提取。