Functional Activation of Peroxisome Proliferator-Activated Receptor α (PPARα) by Environmental Chemicals in Relation to Their Toxicities

Peroxisome proliferator-activated receptor α (PPARα) may work in the processes of both physiological and toxicological response to various endogenous or exogenous substances. The literature on the study of functional activation of PPARα by environmental chemicals in relation to their toxicities were reviewed. Environmental chemicals that were found to induce peroxisomes (peroxisome proliferators) and to activate the function of PPARα included plasticizers, herbicides, and organic solvents that have carboxyl groups in their parent substances or their metabolites. Several studies have showed species differences in the constitutive expression of PPARα and activation of PPARα, which may result in species differences in the induction of transcription of the genes encoding several peroxisomal enzymes. Although much information has supported the view that PPARα is primarily involved in the hepatic carcinogenicity of peroxisome proliferators, conflicting evidence exists. Most of the peroxisome proliferators have been shown to induce reproductive and developmental disorders, which might, in part. be associated with the functional activation of PPARα. Few epidemiological studies on the effect of peroxisome proliferators on humans have been conducted. The effect of perfluorooctanoic acid on humans was evaluated from the aspect of lipid metabolism in one study, which concluded that there was no effect.