PPARalpha agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity.
Oxidative stress has been shown to play an important role in the development of hypertensive renal injury. Peroxisome proliferator-activated receptors alpha (PPARalpha) has antioxidant effect. In this study, we demonstrated that fenofibrate significantly reduced proteinuria, inflammatory cell recruitment and extracellular matrix (ECM) proteins deposition in the kidney of SHRs without apparent effect on blood pressure. To investigate the mechanisms involved, we found that fenofibrate treatment markedly reduced oxidative stress accompanied by reduced activity of renal NAD(P)H oxidase, increased activity of Cu/Zn SOD, and decreased phosphorylation of p38MAPK and JNK in the kidney of SHRs. Taken together, fenofibrate treatment can protect against hypertensive renal injury without affecting blood pressure by inhibiting inflammation and fibrosis via suppression of oxidative stress and MAPK activity.
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong, China.
Xiaoyang
X
Hou
Ying H
YH
Shen
Chuanbao
C
Li
Fei
F
Wang
Cheng
C
Zhang
Peili
P
Bu
Yun
Y
Zhang
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003094:Collagen / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011345:Fenofibrate / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects*; D047493:PPAR alpha / Q000819:agonists*; D051381:Rats; D011918:Rats, Inbred SHR; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; D047493:PPAR alpha; D016212:Transforming Growth Factor beta; D003094:Collagen; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D011345:Fenofibrate