Expression data from hearts (lest ventricle apex) of rats with and without rotenone treatment

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.本研究开展了一项针对雄性Wistar大鼠的亚急性试验：每日以400ppm鱼藤酮（rotenone）对大鼠进行连续1、3或14天给药，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物I（mitochondrial respiratory chain complex I）抑制剂。复合物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。尽管如此，此类抑制剂的安全性仍需进行严格评估。鱼藤酮在多项研究中已被证实具有抗癌活性。基于上述背景，本研究将鱼藤酮作为工具化合物开展实验，旨在筛选合适的候选生物标志物，并深入解析体内给药后，复合物I抑制剂在器官层面所产生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、组织病理学检测，采用荧光激活细胞分选（FACS）技术进行的主要血细胞群体表型分析，以及酶活性测定实验。此外，本研究还测定了基因表达谱，以解析鱼藤酮在分子层面所影响的信号通路与生物学功能。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进行选择。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诱导效应最为显著（1444个差异表达基因）。结合组织病理学结果，上述研究结果证实肝脏为鱼藤酮的靶器官。