Fibrate drugs

Another example is afforded by fibrate drugs and phthalate esters, which bind to the PPAR, in mimicry of polyunsaturated fatty acids. 

PPAR RXR Fibrate drugs, phthalate esters, linoleic acid, arachidonic acid CYP4A, CYP7A (repression), CYP8B, LXR... 

Fibrate drugs are a class of lipid regulatory drugs. They are used to regulate blood lipid and cholesterol levels. They include drugs such as gemfibrozil, ciprofibrate, clofibrate, bezafibrate and fenofibrate (Fig. 1). As noted in Table 1, gemfibrozil (GEM) was identified in /xg/l concentrations in post-STP effluents collected from... 

Fig. 1. Chemical structures of different fibrate drugs known to be peroxisomal proliferators (PP) and of neuroactive drugs. Note that WY-14,643 is a fibrate drug and a potent PP but is not used clinically.

The first PPAR was reported by Issemann and Green30 in rodents. To date, three distinct PPARs, encoded by three distinct genes have been identified PPARa, PPAR/3, and PPARy. These isoforms have different tissue distributions, with PPARa expressed primarily in liver, heart and kidney, PPARy in brown and white adipose tissues, and PPAR/3 (also known as 8) is more ubiquitously expressed, but most abundant in the central nervous system14,17,35. The role of each isoform is beyond the scope of this review as fibrate drugs are mainly PPARa-ligands14, only this form will be examined in detail here. Nevertheless, it should be mentioned that isoforms of the PPAR family have now been cloned from Xenopus laevis, a number of mammals49,50, as well as in some fish species1. 

Compared with mammals, few studies report the impact of fibrate drugs or other PPs in fish, and where reported, the data are equivocal. This may result from the species studied, the normal diet of the species, and the habitat from which the fish comes, all of which are known to impact PPs effects in mammals. 

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