title: Chronic exposure to environmental contaminant nonylphenol exacerbates adenine-induced chronic renal insufficiency: role of signaling pathways and therapeutic impact of rosuvastatin.
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.
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Kun-Chen
authors.initials: KC
authors.lastname: Lin
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Han-Tan
authors.initials: HT
authors.lastname: Chai
authors.forename: Sheng-Ying
authors.initials: SY
authors.lastname: Chung
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Sheung-Fat
authors.initials: SF
authors.lastname: Ko
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Chen
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000225:Adenine; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005355:Fibrosis; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D011493:Protein Kinase C / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068718:Rosuvastatin Calcium; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008562:Membrane Glycoproteins; D010636:Phenols; D011743:Pyrimidines; D013449:Sulfonamides; C025256:nonylphenol; D000068718:Rosuvastatin Calcium; D003404:Creatinine; D009247:NADH, NADPH Oxidoreductases; C500593:Cybb protein, rat; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D000225:Adenine