Continuing exposure to low-dose nonylphenol aggravates adenine-induced chronic renal dysfunction and role of rosuvastatin therapy.
BACKGROUND
Nonylphenol (NP), an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS) synthesis. Chronic exposure to low-dose adenine (AD) has been reported to induce chronic kidney disease (CKD).


METHODS
In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control), group 2 (AD in fodder at a concentration of 0.25%), group 3 (NP: 2 mg/kg/day), group 4 (combined AD & NP), and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day). Treatment was continued for 24 weeks for all animals before being sacrificed.


RESULTS
By the end of 24 weeks, serum blood urea nitrogen (BUN) and creatinine levels were increased in group 4 than in groups 1-3, but significantly reduced in group 5 as compared with group 4 (all p < 0.05). Histopathology scorings of renal-parenchymal and tubular damages were significantly higher in group 4 than in groups 1-3, but remarkably lower in group 5 compared with group 4 (all p < 0.01). Both gene and protein levels of inflammation, oxidative stress, ROS, and cellular apoptosis were remarkably higher in group 4 compared with groups 1-3, but lowered in group 5 than in group 4 (all p < 0.001). Conversely, both gene and protein levels of anti-oxidants, anti-inflammation and anti-apoptosis were markedly increased in group 5 compared with group 4 (all p < 0.001).


CONCLUSIONS
NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.
Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
Chia-Hung
CH
Yen
Cheuk-Kwan
CK
Sun
Steve
S
Leu
Christopher Glenn
CG
Wallace
Yu-Chun
YC
Lin
Li-Teh
LT
Chang
Yung-Lung
YL
Chen
Tzu-Hsien
TH
Tsa
Ying-Hsien
YH
Kao
Pei-Lin
PL
Shao
Chi-Ying
CY
Hsieh
Yen-Ta
YT
Chen
Hon-Kan
HK
Yip
D000225:Adenine / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004781:Environmental Exposure; D005455:Fluorescent Antibody Technique; D005464:Fluorobenzenes / Q000627:therapeutic use*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage* / Q000633:toxicity*; D011507:Proteinuria / Q000097:blood / Q000150:complications; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D015415:Biomarkers; D005464:Fluorobenzenes; D010636:Phenols; D011743:Pyrimidines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C025256:nonylphenol; D000068718:Rosuvastatin Calcium; D003404:Creatinine; D000225:Adenine