الملخص الإنجليزي
Atorvastatin (statin) and gemfibrozil (fibrate) are the most commonly used pharmaceuticals in developed countries for the treatment of hyperlipidemia. Their concentration in aquatic environment are in ng to μg/L ranges. Cholesterol is crucial molecule to all animals; therefore, any disruption of its biosynthesis via these drugs could have pivotal effects in non-target species. Their potential effects on non-target fish species are yet to be fully understood. Therefore, this thesis investigates the effects of atorvastatin (ATV) and gemfibrozil (GEM) and the combination of the two drugs (G+A) on female zebrafish (Danio rerio). This study examined the effects 10x and 1000x relevant to environmental surface-water concentration of ATV and/or GEM (0.15 and 15 μg/L for ATV; 5 and 500μg/L for GEM) on female adult zebrafish after a 28 days water-borne exposure. Moreover, the lipids (cholesterol, triglyceride, steroid hormones), their related genes expression (SREBP-1, SREBP-2, HMGCR-1 and PPAR-α) and muscles atrogen-1 genes were measured. All exposed female zebrafish to ATV, GEM, or G+A resulted in 20- 30% reduction of whole-body cholesterol content and an associated alteration in gene expression related to lipid homeostasis (SREBP-2 and HMGCR-1). Moreover, all treated-female zebrafish had reduction in the whole-body triglyceride content by 50 - 70% and concomitant change in associated gene expression (SREBP-1 and PPARα). Additionally, steroid hormones (testosterone, estradiol and cortisol) were also reduced. We also reported higher atrogin1 mRNA levels in drug-treated zebrafish. Results demonstrated that ATV, GEM and the combination of the two drugs affected fish cholesterol, triglyceride and steroid hormone contents, as well as molecular markers of rhabdomyolysis. This study supports these drugs affecting cholesterol metabolism and steroid production in adult zebrafish. Results indicated that the decline in cortisol may damage the facility of these fish to post a suitable stress response, while the reduction of sex steroids may adversely affect reproduction response. Whether these changes influence fish fitness remains to be determined.
