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

Abstract

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.

Kefir and Its Biological Activities

“…The study showed that the kefir peptides administration at both doses (150 mg/kg and 500 mg/kg) reduced PM4.0-induced inflammatory cell infiltration and inflammatory mediators' expression such as TNF-α, IL-lβ, and IL-4 in lung tissue by inactivating NF-κB signaling. Following the current finding in 2020, Chen et al [122] further studied the effects of the kefir peptides against oxidative stress and inflammation and their protective ability against renal dysfunction on aged salt-induced stroke-prone spontaneously hypertensive (SHRSP) rats. The study revealed a decrease in renal infiltration of inflammatory cells; reactive oxygen species (ROS) levels; histopathological lesions; and the release of vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-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) in salt-induced SHRSP rats.…”

miR-1929-3p Overexpression Alleviates Murine Cytomegalovirus-Induced Hypertensive Myocardial Remodeling by Suppressing Ednra/NLRP3 Inflammasome Activation

“…In this study, we found that the levels of Ednra were significantly increased in the myocardial tissue of MCMV-infected mice, but significantly decreased with miR-1929-3p overexpression, suggesting that miR-1929-3p may influence remodeling of the hypertensive myocardium induced by MCMV infection through its target gene Ednra. Chen et al demonstrated that kefir peptides can exert anti-inflammatory and antifibrotic effects on target organs of spontaneous hypertension by simultaneously reducing the expression of ET-1 and NLRP3 [ 37 ]. Bao et al found that Coxsackie virus B3 can activate inflammatory bodies and induce viral myocarditis [ 38 ].…”

Kefir as a Functional Beverage Gaining Momentum towards Its Health Promoting Attributes

“…Furthermore, the recent COVID-19 viral outbreak calls for non-conventional antiviral agents aiming to reduce the risk of infections and promote patient recovery [64]. Scientific research data support the claim that the regular consumption of kefir can be associated with a wide range of health-promoting affects (Figure 3), including anti-carcinogenic [87], anti-oxidant [89], anti-inflammatory [90], antifibrotic [91], anti-microbial [92], and anti-diabetic [93] effects, as well as improved digestion [94] and lactose tolerance [95], and more recent findings support the link between kefir's probiotic strains and bio-functional metabolites and an enhanced immune system and antiviral activities [65,96]. es 2021, 7, x FOR PEER REVIEW 11 of 15 Boosting and stimulating the immune system is one of the most effective strategies to prevent infections caused by many different pathogens, including viruses [1,12].…”