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Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease
Jing, Mei1,2; Cen, Yun1; Gao, Fangfang1; Wang, Ting1; Jiang, Jinxin1; Jian, Qianqian1; Wu, Liangmiao1,3; Guo, Baojian1; Luo, Fangcheng1,3; Zhang, Gaoxiao1; Wang, Ying4; Xu, Lipeng1; Zhang, Zaijun1; Sun, Yewei1; Wang, Yuqiang1
2021-06-24
Source PublicationFrontiers in Pharmacology
ISSN1663-9812
Volume12
Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage renal failure, but therapeutic options for nephroprotection are limited. Oxidative stress plays a key role in the pathogenesis of DKD. Our previous studies demonstrated that tetramethylpyrazine nitrone (TBN), a novel nitrone derivative of tetramethylpyrazine with potent free radical-scavenging activity, exerted multifunctional neuroprotection in neurological diseases. However, the effect of TBN on DKD and its underlying mechanisms of action are not yet clear. Herein, we performed streptozotocin-induced rat models of DKD and found that TBN administrated orally twice daily for 6 weeks significantly lowered urinary albumin, N-acetyl-β-D-glycosaminidase, cystatin C, malonaldehyde, and 8-hydroxy-2′-deoxyguanosine levels. TBN also ameliorated renal histopathological changes. More importantly, in a nonhuman primate model of spontaneous stage III DKD, TBN increased the estimated glomerular filtration rate, decreased serum 3-nitrotyrosine, malonaldehyde and 8-hydroxy-2′-deoxyguanosine levels, and improved metabolic abnormalities. In HK-2 cells, TBN increased glycolytic and mitochondrial functions. The protective mechanism of TBN might involve the activation of AMPK/PGC-1α-mediated downstream signaling pathways, thereby improving mitochondrial function and reducing oxidative stress in the kidneys of DKD rodent models. These results support the clinical development of TBN for the treatment of DKD.

KeywordDiabetic Kidney Disease Metabolic Abnormalities Mitochondrial Function Nephroprotection Oxidative Stress
DOI10.3389/fphar.2021.680336
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000670650400001
Scopus ID2-s2.0-85109389737
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorSun, Yewei
Affiliation1.Institute of New Drug Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, Jinan University College of Pharmacy, Jinan University, Guangzhou, China
2.Department of Gerontology, The First Affiliated Hospital of Jinan University, Guangzhou, China
3.Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, China
4.Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macao
Recommended Citation
GB/T 7714
Jing, Mei,Cen, Yun,Gao, Fangfang,et al. Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease[J]. Frontiers in Pharmacology,2021,12.
APA Jing, Mei,Cen, Yun,Gao, Fangfang,Wang, Ting,Jiang, Jinxin,Jian, Qianqian,Wu, Liangmiao,Guo, Baojian,Luo, Fangcheng,Zhang, Gaoxiao,Wang, Ying,Xu, Lipeng,Zhang, Zaijun,Sun, Yewei,&Wang, Yuqiang.(2021).Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease.Frontiers in Pharmacology,12.
MLA Jing, Mei,et al."Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease".Frontiers in Pharmacology 12(2021).
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