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Publication : Peroxisome proliferator-activated receptor alpha protects against glomerulonephritis induced by long-term exposure to the plasticizer di-(2-ethylhexyl)phthalate.

First Author  Kamijo Y Year  2007
Journal  J Am Soc Nephrol Volume  18
Issue  1 Pages  176-88
PubMed ID  17135395 Mgi Jnum  J:136008
Mgi Id  MGI:3794933 Doi  10.1681/ASN.2006060597
Citation  Kamijo Y, et al. (2007) Peroxisome proliferator-activated receptor alpha protects against glomerulonephritis induced by long-term exposure to the plasticizer di-(2-ethylhexyl)phthalate. J Am Soc Nephrol 18(1):176-88
abstractText  Safety concerns about di-(2-ethylhexyl)phthalate (DEHP), a plasticizer and a probable endocrine disruptor, have attracted considerable public attention, but there are few studies about long-term exposure to DEHP. DEHP toxicity is thought to involve peroxisome proliferator-activated receptor alpha (PPARalpha), but this contention remains controversial. For investigation of the long-term toxicity of DEHP and determination of whether PPARalpha mediates toxicity, wild-type and PPARalpha-null mice were fed a diet that contained 0.05 or 0.01% DEHP for 22 mo. PPARalpha-null mice that were exposed to DEHP exhibited prominent immune complex glomerulonephritis, most likely related to elevated glomerular oxidative stress. Elevated NADPH oxidase, low antioxidant enzymes, and absence of the PPARalpha-dependent anti-inflammatory effects that normally antagonize the NFkappaB signaling pathway accompanied the glomerulonephritis in PPARalpha-null mice. The results reported here indicate that PPARalpha protects against the nephrotoxic effects of long-term exposure to DEHP.
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