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Publikation Environmental chemicals affect circadian rhythms. An underexplored effect influencing health and fitness in animals and humans(Elsevier, 04/2021) Zheng, Xuehan; Zhang, Kun; Zhao, Yanbin; Fent, KarlCircadian rhythms control the life of virtually all organisms. They regulate numerous aspects ranging from cellular processes to reproduction and behavior. Besides the light-dark cycle, there are additional environmental factors that regulate the circadian rhythms in animals as well as humans. Here, we outline the circadian rhythm system and considers zebrafish (Danio rerio) as a representative vertebrate organism. We characterize multiple physiological processes, which are affected by circadian rhythm disrupting compounds (circadian disrupters). We focus on and summarize 40 natural and anthropogenic environmental circadian disrupters in fish. They can be divided into six major categories: steroid hormones, metals, pesticides and biocides, polychlorinated biphenyls, neuroactive drugs and other compounds such as cyanobacterial toxins and bisphenol A. Steroid hormones as well as metals are most studied. Especially for progestins and glucocorticoids, circadian dysregulation was demonstrated in zebrafish on the molecular and physiological level, which comprise mainly behavioral alterations. Our review summarizes the current state of knowledge on circadian disrupters, highlights their risks to fish and identifies knowledge gaps in animals and humans. While most studies focus on transcriptional and behavioral alterations, additional effects and consequences are underexplored. Forthcoming studies should explore, which additional environmental circadian disrupters exist. They should clarify the underlying molecular mechanisms and aim to better understand the consequences for physiological processes.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Assessment of fibrotic pathways induced by environmental chemicals using 3D-human liver microtissue model(Elsevier, 30.12.2020) Lu, Yan; Messner, Catherine; Suter-Dick, LauraExposure to environmental chemicals, particularly those with persistent and bioaccumulative properties have been linked to liver diseases. Induction of fibrotic pathways is considered as a pre-requirement of chemical induced liver fibrosis. Here, we applied 3D in vitro human liver microtissues (MTs) composed of HepaRG, THP-1 and hTERT-HSC that express relevant hepatic pathways (bile acid, sterol, and xenobiotic metabolism) and can recapitulate key events of liver fibrosis (e.g. extracellular matrix-deposition). The liver MTs were exposed to a known profibrotic chemical, thioacetamide (TAA) and three representative environmental chemicals (TCDD, benzo [a] pyrene (BaP) and PCB126). Both TAA and BaP triggered fibrotic pathway related events such as he-patocellular damage (cytotoxicity and decreased albumin release), hepatic stellate cell activation (transcriptional upregulation of α-SMA and Col1α1) and extracellular matrix remodelling. TCDD or PCB126 at measured con-centrations did not elicit these responses in the 3D liver MTs system, though they caused cytotoxicity in HepaRG monoculture at high concentrations. Reduced human transcriptome (RHT) analysis captured molecular re-sponses involved in liver fibrosis when MTs were treated with TAA and BaP. The results suggest that 3D, multicellular, human liver microtissues represent an alternative, human-relevant, in vitro liver model for assessing fibrotic pathways induced by environmental chemicals.01A - Beitrag in wissenschaftlicher Zeitschrift