Induction of peroxisome proliferator-activated receptor alpha (PPARα)-related enzymes by di(2-ethylhexyl) phthalate (DEHP) treatment in mice and rats, but not marmosets

To clarify species differences in the induction of peroxisome proliferator-activated receptor alpha (PPAR alpha)-related enzymes by di(2-ethylhexyl)phthalate (DEHP) exposure, we investigated the inductions of PPAR alpha and its target genes (mitochondrial medium-chain acyl-CoA dehydrogenase (MCAD) and peroxisomal keto-acyl-CoA thiolase (PT) in liver from mice (CD-1), rats (Sprague-Dawley), and marmosets (Callithrix jacchus) exposed to DEHP. Male mice and rats were treated with 0, 1.25 and 2.5 mmol/kg DEHP for 2 weeks, and marmosets with 0, 0.25, 1.25 and 6.25 mmol/kg DEHP for 15 months by gavage. Hepatic mono(2-ethylhexyl)phthalate (MEHP) levels were significantly higher in mice and rats than in marmosets. The constitutive expression of hepatic PPAR alpha was 5-7 times greater in rats and mice than in marmosets, but DEHP treatment did not induce PPAR alpha-mRNA in all animals. The treatment-induced PT expression detected either by anti-PT antibody or PT-mRNA levels in the liver only from mice and rats, and the induction of the mRNA was greater in the latter than in the former. Thus, DEHP used in this experiment influenced the peroxisomal enzymes in mice and rats, but did not affect the mitochondrial enzymes in any animals or the peroxisomal enzymes in marmosets. These results suggest that there are species differences in the induction of PPAR alpha-related enzymes, especially in peroxisomal enzymes by DEHP treatment, and their underlying mechanism may in part reside in the different constitutive levels of PPAR alpha and different forming levels of MEHP.