Abstract
The aim of this PhD thesis was the molecular characterization of selected bioactive compounds (phytogenics) regarding their protective and toxic effects in cell culture models, the nematode C. elegans as well as in broiler chickens.
In cooperation with the company partner Delacon Biotechnik GmbH, selected phytogenic substances were evaluated regarding to their protective or potentially toxic effects. In detail, the positive effect of ginseng extract was demonstrated under heat stress conditions in Caco-2 cells, C. elegans and broiler chickens. It was shown that the relative mRNA expression of selected heat stress protein as well as tight junction genes were significantly altered. C. elegans experiments additionally revealed that this regulation is dependent on the FOXO transcription factor daf-16. In the feeding study with broiler chickens, supplemented ginseng extract showed an improved feed conversion rate and increased weight gain. Furthermore, potential toxic effects of essential oils (rosemary, citrus, eucalyptus) were evaluated in cell culture, C. elegans as well as HET-CAM. Positive effects of essential oils are well known - however, there is little data regarding adverse effects. It was shown that the selected essential oils exhibit toxic potential in all tested model systems, even at low concentrations. C. elegans also revealed a significant upregulation of oxidative and xenobiotic stress genes. The regulation was furthermore altered by the daf-16 and skn-1 mediated pathways. The correlation of the calculated LD50 values resulting from the model organisms were in concordance with existing data from rat studies. Thus, also showing promising indicators for a future reduction of animal testing in that sector.
The reduction and/or replacement of animal testing in the field of toxicology was also addressed. Besides ethical concerns and high costs, the steadily increasing number of substances to be
tested is a particular challenge. Alternative, low cost and reliable high-throughput systems could fill the huge gap between classic cell culture and animal trials.
In cooperation with the company partner Delacon Biotechnik GmbH, selected phytogenic substances were evaluated regarding to their protective or potentially toxic effects. In detail, the positive effect of ginseng extract was demonstrated under heat stress conditions in Caco-2 cells, C. elegans and broiler chickens. It was shown that the relative mRNA expression of selected heat stress protein as well as tight junction genes were significantly altered. C. elegans experiments additionally revealed that this regulation is dependent on the FOXO transcription factor daf-16. In the feeding study with broiler chickens, supplemented ginseng extract showed an improved feed conversion rate and increased weight gain. Furthermore, potential toxic effects of essential oils (rosemary, citrus, eucalyptus) were evaluated in cell culture, C. elegans as well as HET-CAM. Positive effects of essential oils are well known - however, there is little data regarding adverse effects. It was shown that the selected essential oils exhibit toxic potential in all tested model systems, even at low concentrations. C. elegans also revealed a significant upregulation of oxidative and xenobiotic stress genes. The regulation was furthermore altered by the daf-16 and skn-1 mediated pathways. The correlation of the calculated LD50 values resulting from the model organisms were in concordance with existing data from rat studies. Thus, also showing promising indicators for a future reduction of animal testing in that sector.
The reduction and/or replacement of animal testing in the field of toxicology was also addressed. Besides ethical concerns and high costs, the steadily increasing number of substances to be
tested is a particular challenge. Alternative, low cost and reliable high-throughput systems could fill the huge gap between classic cell culture and animal trials.
| Originalsprache | Englisch |
|---|---|
| Qualifikation | Dr. techn. |
| Gradverleihende Hochschule |
|
| Betreuer/-in / Berater/-in |
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| Datum der Bewilligung | 28 Sep. 2021 |
| Publikationsstatus | Veröffentlicht - Sep. 2021 |