PMID- 32858955 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201020 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 9 IP - 9 DP - 2020 Aug 26 TI - Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Kefir Peptides on Salt-Induced Renal Vascular Damage and Dysfunction in Aged Stroke-Prone Spontaneously Hypertensive Rats. LID - 10.3390/antiox9090790 [doi] LID - 790 AB - 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 alpha-smooth muscle actin (alpha-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-beta (TGF-beta); 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. FAU - Chen, Yu-Hsuan AU - Chen YH AD - Department of Life Sciences, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. AD - Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung 402, Taiwan. AD - Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Health Research Institutes, Taichung 402, Taiwan. FAU - Chen, Hsiao-Ling AU - Chen HL AD - Department of Biomedical Sciences, Da-Yeh University, Changhwa 515, Taiwan. FAU - Fan, Hueng-Chuen AU - Fan HC AUID- ORCID: 0000-0003-3485-7558 AD - Department of Life Sciences, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. AD - Department of Pediatrics, Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan. AD - Department of Rehabilitation, Jen-Teh Junior College of Medicine, Miaoli 356, Taiwan. FAU - Tung, Yu-Tang AU - Tung YT AUID- ORCID: 0000-0002-4780-6496 AD - Department of Life Sciences, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. AD - Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 110, Taiwan. FAU - Kuo, Chia-Wen AU - Kuo CW AUID- ORCID: 0000-0002-3717-1191 AD - Department of Life Sciences, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. AD - Department of Internal Medicine, Department of Orthopaedic Surgery, Taichung Armed Forces General Hospital, Taichung 411, Taiwan. FAU - Tu, Min-Yu AU - Tu MY AD - Department of Life Sciences, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. AD - Aviation Physiology Research Laboratory, Kaohsiung Armed Forces General Hospital Gangshan Branch, Kaohsiung 820, Taiwan. FAU - Chen, Chuan-Mu AU - Chen CM AUID- ORCID: 0000-0003-2461-9150 AD - Department of Life Sciences, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. AD - The iEGG and Animal Biotechnology Center, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. LA - eng GR - MOST-104-2313-B-005-043-MY3/The Ministry of Science and Technology of Taiwan/ GR - MOE-109-S-0023-A/The Ministry of Education of Taiwan/ PT - Journal Article DEP - 20200826 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC7555286 OTO - NOTNLM OT - chronic kidney disease OT - glomerulosclerosis OT - kefir peptides OT - renal dysfunction OT - stroke-prone spontaneously hypertensive rats COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2020/08/30 06:00 MHDA- 2020/08/30 06:01 PMCR- 2020/08/26 CRDT- 2020/08/30 06:00 PHST- 2020/07/11 00:00 [received] PHST- 2020/08/19 00:00 [revised] PHST- 2020/08/21 00:00 [accepted] PHST- 2020/08/30 06:00 [entrez] PHST- 2020/08/30 06:00 [pubmed] PHST- 2020/08/30 06:01 [medline] PHST- 2020/08/26 00:00 [pmc-release] AID - antiox9090790 [pii] AID - antioxidants-09-00790 [pii] AID - 10.3390/antiox9090790 [doi] PST - epublish SO - Antioxidants (Basel). 2020 Aug 26;9(9):790. doi: 10.3390/antiox9090790.