Chronic exposure to environmental contaminant nonylphenol exacerbates adenine-induced chronic renal insufficiency: role of signaling pathways and therapeutic impact of rosuvastatin.

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Title:	Chronic exposure to environmental contaminant nonylphenol exacerbates adenine-induced chronic renal insufficiency: role of signaling pathways and therapeutic impact of rosuvastatin.
Authors:	Yen CH;Lin KC;Leu S;Sun CK;Chang LT;Chai HT;Chung SY;Chang HW;Ko SF;Chen YT;Yip HK
Date:	2012-08
Issue Date:	2012-09-05T07:10:21Z (UTC)
Abstract:	Although chronic exposure to environmental contaminants is hazardous to health, the association between chronic kidney disease (CKD) and nonylphenol (NP), a common environmental compound, remains unclear. This study tested the hypothesis that chronic NP exposure aggravated adenine (AD)-induced CKD that could be mitigated with rosuvastatin treatment. Fifty Wistar rats were randomly (n=10/each group) categorized into normal controls (N(C)), NP only (2.0mg/kg/day), AD only (0.25% AD in fodder), combined NP-AD, and NP-AD with rosuvastatin (20.0mg/kg/day) (NP-AD-R(OSU)). All animals received treatment for 24 weeks prior to being sacrificed. Results showed that ratio of urine protein to creatinine were increased in NP-AD group than in groups N(C), NP, and AD, but reduced in NP-AD-R(OSU) group compared with NP-AD group (all p<0.003). Protein expression of TGF-β and phosphorylated Smad3, indexes of tissue fibrosis, were increased in NP-AD group than in groups N(C), NP and AD, but reduced in NP-AD-R(OSU) group compared with NP-AD group (all p<0.001). BMP-2 and phosphorylated Smad1/5, two indicators of anti-fibrosis, were lower in NP-AD group than in groups N(C), NP and AD, but higher in NP-AD-R(OSU) group compared with NP-AD group (all p<0.001). Protein expressions of JNK and PKC-α in membranous compartment were higher in group NP-AD than in groups N(C), NP and AD, but reduced in NP-AD-R(OSU) group compared with NP-AD group (all p<0.001). More TGF-β+cells but less BMP-2+, CD31+, vWF+and GR+cells were noted in groups AD and NP-AD than in groups N(C), NP and NP-AD-R(OSU) (all p<0.04). In conclusion, NP exposure worsened aggravated AD-induced CKD that could be ameliorated with rosuvastatin treatment.
Relation:	Eur J Pharm Sci. 2012 Aug 15;46(5):455-67. Epub 2012 Mar 29.
Appears in Collections:	[Department of Nursing] Papers

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