Low-molecular-weight chitosan scavenges methylglyoxal and N 蔚-(carboxyethyl)lysine, the major factors contributing to the pathogenesis of nephropathy

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• 作者：Chu-Kuang Chou ; Shih-Ming Chen ; Yi-Chieh Li ; Tzu-Chuan Huang ; Jen-Ai Lee
• 关键词：Nephropathy ; Methylglyoxal ; N 蔚 ; (carboxyethyl)lysine ; Low ; molecular ; weight chitosan
• 刊名：SpringerPlus
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：4
• 期：1
• 全文大小：1283KB
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• 作者单位：Chu-Kuang Chou (1) (3)
  Shih-Ming Chen (2)
  Yi-Chieh Li (2)
  Tzu-Chuan Huang (2)
  Jen-Ai Lee (2)
  
  1. Chia-Yi Christian Hospital, No. 539 Jhongsiao Rd., Chia-Yi City, 60002, Taiwan
  3. Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei City, 10002, Taiwan
  2. School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250 Wuxing St., Taipei, 11031, Taiwan, ROC
  
• 刊物类别：Science, general;
• 刊物主题：Science, general;
• 出版者：Springer International Publishing
• ISSN：2193-1801

文摘

Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction. Accumulation of MG and its downstream metabolite N 蔚-(carboxyethyl)lysine (CEL) has been identified in several variations of nephropathy, including diabetic, hypertensive, and gentamicin-induced nephropathies. In this study, we investigated the effects of low-molecular-weight chitosan (lmw-chitosan) on MG-induced carbonyl stress in aristolochic acid-induced nephropathy. We used a buffer to investigate whether MG could be scavenged by lmw-chitosan in vitro. In addition, we also used a mouse model of aristolochic acid-induced nephropathy, which exhibits 12-fold greater accumulation of MG in the kidneys than that found in control animals, to examine whether lmw-chitosan could decrease MG levels in vivo. Examination of the binding of lmw-chitosan with MG in vitro demonstrated that the concentration of lmw-chitosan necessary to achieve 50% inhibition was 4.60 碌g mL鈭?. Treatment with lmw-chitosan (500 mg kg鈭? day鈭? orally) for 14 days significantly decreased renal MG accumulation from 212.86 卤 24.34 to 86.15 卤 33.79 碌g g鈭? protein (p < 0.05) and CEL levels from 4.60 卤 0.27 to 2.84 卤 0.28 碌mol 碌g鈭? protein (p < 0.05) in the aristolochic acid-induced nephropathy model. These data suggest that lmw-chitosan might represent a novel treatment modality for MG-related diseases such as nephropathy. Keywords Nephropathy Methylglyoxal N 蔚-(carboxyethyl)lysine Low-molecular-weight chitosan