PMID: 9547862Apr 21, 1998Paper

Receptor and nonreceptor-mediated organ-specific toxicity of di(2-ethylhexyl)phthalate (DEHP) in peroxisome proliferator-activated receptor alpha-null mice

Toxicologic Pathology
J M WardF J Gonzalez

Abstract

The peroxisome proliferator-activated receptor alpha (PPAR alpha) is the mediator of the biological effects of peroxisome proliferators through control of gene transcription. To determine if the toxic effects of di(2-ethylhexyl)phthalate (DEHP) are mediated by PPAR alpha, we examined its effect in PPAR alpha-null mice. Male Sv/129 mice, PPAR alpha-null (-/-) or wild-type (+/+) were fed ad libitum either a control diet or one containing 12,000 ppm DEHP for up to 24 wk. Significant body weight loss and high mortality was observed in (+/+) mice fed DEHP. By 16 wk, all DEHP-fed (+/+) mice had died of cystic renal tubular disease. In contrast, the (-/-) mice fed DEHP had no changes in body weight until later in the study nor increased mortality. Histologically, (+/+) mice fed DEHP had typical toxic lesions in liver, kidney, and testis while (-/-) mice fed DEHP had no toxic liver lesions but did show evidence of toxicity in kidney and testis after 4-8 wk of feeding, which progressed into moderate lesions by 24 wk. Analysis of hepatic and renal mRNAs showed a typical pleiotropic response in gene expression in the DEHP-fed (+/+) mice that was absent in the DEHP-fed (-/-) mice. These results provide evidence that PPAR alpha mediates the...Continue Reading

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Citations

Feb 17, 2001·Journal of Applied Toxicology : JAT·R H McKeeM Stanley
Oct 2, 2002·Journal of Applied Toxicology : JAT·R H McKeeA W Lington
Mar 17, 2004·Reproductive Toxicology·Rochelle W TylJohn H Butala
Sep 15, 2004·Toxicology and Applied Pharmacology·Christopher H Hurst, David J Waxman
Sep 15, 2004·Toxicology and Applied Pharmacology·Jonathan M Shipley, David J Waxman
Apr 20, 2004·Toxicology Letters·Ruth A RobertsEric Boitier
Apr 23, 2003·Molecular and Cellular Endocrinology·Tara Lovekamp-SwanBarbara J Davis
Apr 27, 2001·Toxicology Letters·R A RobertsG Orphanides
Aug 21, 2003·Toxicology Letters·Yoshiko YokoyamaKazutaka Kano
Apr 12, 2001·Reproductive Toxicology·L J HushkaR H McKee
Feb 26, 2000·Reproductive Toxicology·S J WatermanR H McKee
Jun 5, 2003·Biochimica Et Biophysica Acta·Jeffrey M PetersFrank J Gonzalez
Nov 25, 2000·Clinical and Experimental Immunology·Q YangJ W Depierre
Jun 24, 2008·Journal of Toxicology and Environmental Health. Part a·Anthony B DeAngeloMichael H George
Oct 19, 2010·Journal of Toxicology and Environmental Health. Part a·Na Young KimHyung Sik Kim
Jun 14, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Christopher H Hurst, David J Waxman
Jul 14, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Abdelali LehraikiChristine Levacher
Nov 25, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Bethany R HannasVickie S Wilson
Jan 30, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Barbara A WetmoreRussell S Thomas
Feb 28, 2003·Biology of Reproduction·Jannette M DufourKwan Hee Kim
Nov 27, 2004·Biology of Reproduction·Nandini BhattacharyaKwan Hee Kim
Sep 2, 2004·Molecular and Cellular Biology·Harm de WaardGijsbertus T J van der Horst
Oct 20, 2005·Occupational and Environmental Medicine·R Hauser, A M Calafat
Jun 8, 2012·Environmental Health Perspectives·Nikki Gillum PosnackNarine Sarvazyan
Feb 8, 2003·Environmental Health Perspectives·Tara Lovekamp-Swan, Barbara J Davis

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