Human pharmaceuticals in the environment: Effects of fibrate drugs on two fish species

Human pharmaceuticals have been reported in the aquatic environment but information pertaining to their effect(s) in aquatic non-target species was scarce when this project was initiated. The two main objectives of this research were to determine if these new emerging contaminants are available to aquatic species and to assess if exposure can lead to unfavourable effects in two fish species, the goldfish (Carassius auratus) and the rainbow trout (Oncorhynchus mykiss).;Most studies were done with the fibrate drug gemfibrozil (GEM), although the other fibrates bezafibrate (BEZA), clofibrate (CLO) and fenofibrate (FENO) were used for specific experiments. Waterborne GEM exposure resulted in bioconcentration factors up to 500 in goldfish using LC-MS/MS estimates. Results provided strong evidence that environmental concentrations of GEM are not indicative of plasme concentration in fish. Tissue distribution for the three peroxisome proliferator-activated receptors (PPARs) subtypes were established in goldfish and rainbow trout by estimating mRNA levels using reverse-transcriptase PCR (RT-PCR). The monitoring of PPARalpha mRNA was found not to be a good indicator of GEM exposure as mRNA levels were not modified. Interestingly PPARbeta mRNA appears to be modulated in comparable ways in the two species and PPARgamma was affected but only in rainbow trout. Identified potentially harmful effects resulting from exposure to fibrate drugs include (1) a challenged hepatic antioxidant defense system in goldfish exposed to an environmentally relevant concentration of GEM determined using spectrophotometric assays and (2) an impaired cortisol response in rainbow trout exposed to high concentrations of CLO and FENO determined through in-vitro head kidney cell stimulation. A mechanistic approach to understand the effects of fibrate drugs allowed identifying potential target steps of corticosteroidogenesis, hence contributing to the understanding of basic endocrinology. This thesis is an important contribution to the emerging field of the effects of pharmaceuticals in the aquatic environment as it provides evidence that environmental concentrations significantly underestimate in-vivo drug levels and that exposure to human drugs may challenge or impair essential physiological functions in fish. Future research should focus on assessing effects over longer periods of time and at lower concentrations.