Tilbake til søkeresultatene


Modulation of hepatic peroxisome proliferator-activated receptor isoforms and lipid peroxidation by Tributyltin in Atlantic salmon in vitro

Tildelt: kr 0,13 mill.

Organotin compounds, such as tributyltin (TBT) are one of the main marine contaminants. They are used as antifouling biocides in marine paints for ships and are continuously released to the enviroment. TBT is a known endocrine disruptor, i.e. compounds th at disrupt the hormonal equilibrium in organisms. In aquatic invertebrates, it induces irreversible sexual abnormality in females and this generally termed imposex and by this way negatively influences the reproduction of these species. However, the mecha nisms of endocrine disruptive effects of TBT have not been fully clarified. Through activation of nuclear receptors and other transcription factors, xenobiotics like TBT can produce alteration in target gene expression. Recently, in vivo interennal and he patic gene expression patterns of steroid acute regulatory (StAR) protein, P450scc, CYP11b, steroidogenic factor-1 (SF-1), glucocorticoid receptor (GlucR) and peroxisome proliferator activated receptor (PPAR) isoforms were determined as results of TBT exp osure to salmon. TBT was also found to be an agonist for PPAR receptor, suggesting that TBT may exert endocrine disrupting effects through modulation of lipid peroxidation by targeting the PPAR signalling pathway and beyond aromatase inhibition. The main objective of the present project is to study is to validate our recent in vivo findings, by evaluating the effects of TBT on PPAR activations and transcriptional regulation, oxidative stress and lipid peroxidation in primary culture of salmon hepatocytes. Our results will show gene and protein expression patterns in the lipid peroxidation signalling and oxidative stress after TBT exposure and thus will help to clarify this part of endocrine disruptive effect of TBT in marine organisms.