Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression

被引：148

作者：

Chen, Hua ^{[1
]}

Cao, Gang ^{[3
]}

Chen, Dan-Qian ^{[1
]}

Wang, Ming ^{[1
]}

Vaziri, Nosratola D. ^{[2
]}

Zhang, Zhi-Hao ^{[4
]}

Mao, Jia-Rong ^{[5
]}

Bai, Xu ^{[6
]}

Zhao, Ying-Yong ^{[1
]}

机构：

[1] Northwest Univ, Key Lab Resource Biol & Biotechnol Western China, Minist Educ, Coll Life Sci, 229 Taibai North Rd, Xian 710069, Shaanxi, Peoples R China

[2] Univ Calif Irvine, Sch Med, Div Nephrol & Hypertens, MedSci 1, C352,UCI Campus, Irvine, CA 92897 USA

[3] Zhejiang Chinese Med Univ, Res Ctr TCM Proc Technol, 548 Binwen Rd, Hangzhou 310053, Zhejiang, Peoples R China

[4] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, Dept Biomol Sci, Oxford, MS 38677 USA

[5] Shaanxi Inst Tradit Chinese Med, Affiliated Hosp, Dept Nephrol, 2 Xihuamen, Xian 710003, Shaanxi, Peoples R China

[6] Waters Technol Shanghai Ltd, Solut Ctr, 1000 Jinhai Rd, Shanghai 201203, Peoples R China

来源：

REDOX BIOLOGY | 2016年 / 10卷

基金：

中国国家自然科学基金;

关键词：

Chronic kidney disease; Metabolomics; Inflammation; Renal fibrosis; Lipid metabolism; Biomarker; SENSITIVITY MASS-SPECTROMETRY; CHRONIC-RENAL-FAILURE; ARISTOLOCHIC ACID; EXPERIMENTAL-MODEL; OXIDATIVE STRESS; GENE-EXPRESSION; NEPHROTOXICITY; METABONOMICS; BIOMARKERS; FIBROSIS;

D O I：

10.1016/j.redox.2016.09.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Early detection is critical in prevention and treatment of kidney disease. However currently clinical laboratory and histopathological tests do not provide region-specific and accurate biomarkers for early detection of kidney disease. The present study was conducted to identify sensitive biomarkers for early detection and progression of tubulo-interstitial nephropathy in aristolochic acid I-induced rats at weeks 4, 8 and 12. Biomarkers were validated using aristolochic acid nephropathy (AAN) rats at week 24, adenine-induced chronic kidney disease (CKD) rats and CKD patients. Compared with control rats, AAN rats showed anemia, increased serum urea and creatinine, progressive renal interstitial fibrosis, activation of nuclear factor-kappa B, and up-regulation of proinflammatory, pro-oxidant, and pro-fibrotic proteins at weeks 8 and 12. However, no significant difference was found at week 4. Metabolomics identified 12-ketodeoxycholic acid, taurochenodesoxycholic acid, LPC(15:0) and docosahexaenoic acid as biomarkers for early detection of tubulo-interstitial nephropathy. With prolonging aristolochic acid I exposure, LPE(20:2), cholic acid, chenodeoxycholic acid and LPC(17:0) were identified as biomarkers for progression from early to advanced AAN and lysoPE(22:5), indoxyl sulfate, uric acid and creatinine as biomarkers of advanced AAN. These biomarkers were reversed by treatment of irbesartan and ergone in AAN rats at week 24 and adenine-induced CKD rats. In addition, these biomarkers were also reversed by irbesartan treatment in CKD patients.

引用

页码：168 / 178

页数：11

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