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Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Kefir Peptides on Salt-Induced Renal Vascular Damage and Dysfunction in Aged Stroke-Prone Spontaneously Hypertensive Rats

by 1,2,3,†, 4,†, 1,5,6,7,†, 1,8, 1,9,10, 1,11 and 1,12,*
1
Department of Life Sciences, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan
2
Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung 402, Taiwan
3
Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Health Research Institutes, Taichung 402, Taiwan
4
Department of Biomedical Sciences, Da-Yeh University, Changhwa 515, Taiwan
5
Department of Pediatrics, Tungs’ Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan
6
Department of Medical Research, Tungs’ Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan
7
Department of Rehabilitation, Jen-Teh Junior College of Medicine, Miaoli 356, Taiwan
8
Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 110, Taiwan
9
Department of Internal Medicine, Taichung Armed Forces General Hospital, Taichung 411, Taiwan
10
Department of Orthopaedic Surgery, Taichung Armed Forces General Hospital, Taichung 411, Taiwan
11
Aviation Physiology Research Laboratory, Kaohsiung Armed Forces General Hospital Gangshan Branch, Kaohsiung 820, Taiwan
12
The iEGG and Animal Biotechnology Center, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this study.
Antioxidants 2020, 9(9), 790; https://doi.org/10.3390/antiox9090790
Received: 11 July 2020 / Revised: 19 August 2020 / Accepted: 21 August 2020 / Published: 26 August 2020
(This article belongs to the Special Issue Oxidative Stress in Vascular Pathophysiology)
The increased prevalence of renal dysfunction and chronic kidney disease (CKD) and the high costs and poor outcomes of treatment are a significant health issue. The consequence of chronic high blood pressure is the increased prevalence of target organ end-stage renal disease, which has been proven to be a strong independent risk factor for adverse cardiovascular disease. A previous study showed that kefir products have anti-inflammatory and anti-hypertensive activities and immunological modulation functions. However, no data regarding the beneficial effects of kefir peptides (KPs) on salt-induced renal damage or related kidney diseases are available. In this study, KPs were orally administered to aged salt-induced stroke-prone spontaneously hypertensive (SHRSP) rats, and the effects of KPs against inflammation and oxidative stress and their ability to protect against renal dysfunction were evaluated. Fifty-five-week-old SHRSP rats under induction with 1% NaCl in drinking water for 4 weeks showed multiple renal injuries with increased renal inflammation, fibrosis, oxidative stress, tubular atrophy, and glomerulosclerosis. In contrast, oral gavage with KPs reduced the urine protein to creatinine (UPC) ratio, the fractional excretion of electrolytes (FeNa and FeCl), extracellular matrix deposition, and the interstitial fibrotic α-smooth muscle actin (α-SMA) levels in salt-induced SHRSP rats. The renal infiltration of inflammatory cells; the release of monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), endothelin-1 (ET-1), and the cytokine nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) and transforming growth factor-β (TGF-β); the reactive oxygen species (ROS) levels; and histopathological lesions were also decreased in salt-induced SHRSP rats. Furthermore, KP treatment significantly increased the renal superoxide dismutase (SOD) activity and the glomerular filtration rate (GFR), which exerted potent protection against salt-induced chronic kidney disease in SHRSP rats. The results of this study suggest that KPs ameliorate salt-induced renal damage, tubular atrophy, and glomerular dysfunction through anti-inflammatory, antioxidative stress, and antifibrotic activities, and might be a promising protective agent against high salt-induced renovascular-related diseases. View Full-Text
Keywords: kefir peptides; chronic kidney disease; glomerulosclerosis; stroke-prone spontaneously hypertensive rats; renal dysfunction kefir peptides; chronic kidney disease; glomerulosclerosis; stroke-prone spontaneously hypertensive rats; renal dysfunction
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MDPI and ACS Style

Chen, Y.-H.; Chen, H.-L.; Fan, H.-C.; Tung, Y.-T.; Kuo, C.-W.; Tu, M.-Y.; Chen, C.-M. Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Kefir Peptides on Salt-Induced Renal Vascular Damage and Dysfunction in Aged Stroke-Prone Spontaneously Hypertensive Rats. Antioxidants 2020, 9, 790. https://doi.org/10.3390/antiox9090790

AMA Style

Chen Y-H, Chen H-L, Fan H-C, Tung Y-T, Kuo C-W, Tu M-Y, Chen C-M. Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Kefir Peptides on Salt-Induced Renal Vascular Damage and Dysfunction in Aged Stroke-Prone Spontaneously Hypertensive Rats. Antioxidants. 2020; 9(9):790. https://doi.org/10.3390/antiox9090790

Chicago/Turabian Style

Chen, Yu-Hsuan; Chen, Hsiao-Ling; Fan, Hueng-Chuen; Tung, Yu-Tang; Kuo, Chia-Wen; Tu, Min-Yu; Chen, Chuan-Mu. 2020. "Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Kefir Peptides on Salt-Induced Renal Vascular Damage and Dysfunction in Aged Stroke-Prone Spontaneously Hypertensive Rats" Antioxidants 9, no. 9: 790. https://doi.org/10.3390/antiox9090790

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