Project description: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.
Project description: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.
Project description: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.
Project description:Comparison of small RNA expression profiles from C. elegans at different time points after Rotenone and Dimethylsulfoxid (DMSO) treatment. The RNA-seq data comprise 5 time points (6 hours, 1, 2, 3 and 5 days) treated with Rotenone and DMSO as well as 2 time points (3 and 5 days) with an additional H2O treatment. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Comparison of small RNA expression profiles from C. elegans after Rotenone and Dimethylsulfoxid (DMSO) treatment. The RNA-seq data comprise 4 age groups (1, 5, 10 and 20 days) and two different treatments (Rotenone and DMSO). Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Comparison of gene expression profiles from C. elegans at different time points after Rotenone and Dimethylsulfoxid (DMSO) treatment. The RNA-seq data comprise 5 time points (6 hours, 1, 2, 3 and 5 days) treated with Rotenone and DMSO as well as 2 time points (3 and 5 days) with an additional H2O treatment. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Comparison of small RNA expression profiles from C. elegans of Rotenone and Dimethylsulfoxid (DMSO) treated animals. The RNA-seq data comprise two age groups (5 and 15 days) and two different conditions (rotenone, DMSO). Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Comparison of Danio rerio brain for 2 age groups treated with Rotenone. The RNA-seq data comprises two age groups treated with different Rotenone dose levels. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Comparison of gene expression profiles from C. elegans of Rotenone and Dimethylsulfoxid (DMSO) treated animals. The RNA-seq data comprise two age groups (5 and 15 days) and two different conditions (rotenone, DMSO). Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)