scholarly journals Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity

2022 ◽  
Vol 23 (1) ◽  
pp. 502
Author(s):  
Hyesook Lee ◽  
Seon Yeong Ji ◽  
Hyun Hwangbo ◽  
Min Yeong Kim ◽  
Da Hye Kim ◽  
...  
Keyword(s):  
Protective Effect ◽  
Renal Injury ◽  
Salt Intake ◽  
Protective Efficacy ◽  
High Salt ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Renal Hypertrophy ◽  
High Salt Intake

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with L. brevis BJ20 and L. plantarum BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.

scholarly journals NOX4/H 2 O 2 /mTORC1 Pathway in Salt-Induced Hypertension and Kidney Injury

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 133-143 ◽  
Author(s):  
Vikash Kumar ◽  
Theresa Kurth ◽  
Nadezhda N. Zheleznova ◽  
Chun Yang ◽  
Allen W. Cowley
Keyword(s):  
Renal Injury ◽  
Immune Cell ◽  
Salt Intake ◽  
Chronic Phase ◽  
Kidney Injury ◽  
High Salt ◽  
High Salt Intake ◽  
Induced Hypertension

We have reported that a high-salt (4.0% NaCl) dietary intake activates mTORC1 and inhibition of this pathway with rapamycin blunts the chronic phase of salt-induced hypertension and renal injury in Dahl salt-sensitive (SS) rats. In SS rats, high-salt intake is known to increase the renal production of H 2 O 2 by NOX4, the most abundant NOX isoform in the kidney, and the global knockout of NOX4 blunts salt-sensitivity in these rats. Here, we explored the hypothesis that elevations of H 2 O 2 by NOX4 in high-salt fed SS rat stimulate mTORC1 for the full development of salt-induced hypertension and renal injury. Our in vitro studies found that H 2 O 2 activates mTORC1 independent of PI3K/AKT and AMPK pathways. To determine the in vivo relevance of NOX4/H 2 O 2 /mTORC1 in the salt-induced hypertension, SS- Nox4 knockout (SS Nox4 −/− ) rats were daily administrated with vehicle/rapamycin fed a high-salt diet for 21 days. Rapamycin treatment of SS Nox4−/− rats had shown no augmented effect on the salt-induced hypertension nor upon indices of renal injury. Significant reductions of renal T lymphocyte and macrophage together with inhibition of cell proliferation were observed in rapamycin treated rats suggesting a role of mTORC1 independent of NOX4 in the proliferation of immune cell. Given the direct activation of mTORC1 by H 2 O 2 and absence of any further protection from salt-induced hypertension in rapamycin-treated SS Nox4 −/− rats, we conclude that NOX4-H 2 O 2 is a major upstream activator of mTORC1 that contributes importantly to salt-induced hypertension and renal injury in the SS rat model.

Salt sensitivity in experimental thyroid disorders in rats

2011 ◽  
Vol 301 (2) ◽  
pp. E281-E287 ◽  
Author(s):  
Rocío Perez-Abud ◽  
Isabel Rodríguez-Gómez ◽  
Ana Belén Villarejo ◽  
Juan Manuel Moreno ◽  
Rosemary Wangensteen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Injury ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Thyroid Disorders ◽  
High Salt Intake ◽  
Male Wistar Rats ◽  
Experimental Thyroid ◽  
And Oxidative Stress

This study assessed salt sensitivity, analyzing the effects of an increased saline intake on hemodynamic, morphological, and oxidative stress and renal variables in experimental thyroid disorders. Six groups of male Wistar rats were used: control, hypothyroid, hyperthyroid, and the same groups treated with salt (8% via food intake). Body weight, blood pressure (BP), and heart rate (HR) were recorded weekly for 6 wk. Finally, BP and HR were recorded directly, and morphological, metabolic, plasma, and renal variables were measured. High-salt intake increased BP in thyroxine-treated rats but not in control or hypothyroid rats. High-salt intake increased cardiac mass in all groups, with a greater increase in hyperthyroid rats. Urinary isoprostanes and H2O2 were higher in hyperthyroid rats and were augmented by high-salt intake in all groups, especially in hyperthyroid rats. High-salt intake reduced plasma thyroid hormone levels in hyperthyroid rats. Proteinuria was increased in hyperthyroid rats and aggravated by high-salt intake. Urinary levels of aminopeptidases (glutamyl-, alanyl-, aspartyl-, and cystinylaminopeptidase) were increased in hyperthyroid rats. All aminopeptidases were increased by salt intake in hyperthyroid rats but not in hypothyroid rats. In summary, hyperthyroid rats have enhanced salt sensitivity, and high-salt intake produces increased BP, cardiac hypertrophy, oxidative stress, and signs of renal injury. In contrast, hypothyroid rats are resistant to salt-induced BP elevation and renal injury signs. Urinary aminopeptidases are suitable biomarkers of renal injury.

scholarly journals Stimulation of Epithelial Sodium Channels in Endothelial Cells by Bone Morphogenetic Protein-4 Contributes to Salt-Sensitive Hypertension in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xu Yang ◽  
Na Niu ◽  
Chen Liang ◽  
Ming-Ming Wu ◽  
Liang-Liang Tang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Bone Morphogenetic Protein ◽  
Salt Intake ◽  
High Salt ◽  
Bone Morphogenetic Protein 4 ◽  
Sodium Influx ◽  
Morphogenetic Protein ◽  
High Salt Intake ◽  
Stimulation Of

Previous studies have shown that high salt induces artery stiffness by causing endothelial dysfunction via increased sodium influx. We used our unique split-open artery technique combined with protein biochemistry and in vitro measurement of vascular tone to test a hypothesis that bone morphogenetic protein 4 (BMP4) mediates high salt-induced loss of vascular relaxation by stimulating the epithelial sodium channel (ENaC) in endothelial cells. The data show that high salt intake increased BMP4 both in endothelial cells and in the serum and that exogenous BMP4 stimulated ENaC in endothelial cells. The data also show that the stimulation is mediated by p38 mitogen-activated protein kinases (p38 MAPK) and serum and glucocorticoid-regulated kinase 1 (Sgk1)/neural precursor cell expressed developmentally downregulated gene 4-2 (Nedd4-2) (Sgk1/Nedd4-2). Furthermore, BMP4 decreased mesenteric artery relaxation in a benzamil-sensitive manner. These results suggest that high salt intake stimulates endothelial cells to express and release BMP4 and that the released BMP4 reduces artery relaxation by stimulating ENaC in endothelial cells. Therefore, stimulation of ENaC in endothelial cells by BMP4 may serve as another pathway to participate in the complex mechanism of salt-sensitive (SS) hypertension.

Abstract 451: Depletion of Macrophage Prevents Exacerbated Renal Injury and Hypertension Induced by Degeneration of Trpv1-positive Nerves in Rats Subjected to Renal Ischemic Reperfusion and Salt Load

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Shuang-Quan Yu ◽  
Donna H Wang
Keyword(s):  
Renal Injury ◽  
Salt Intake ◽  
Ischemia Reperfusion ◽  
Tissue Growth ◽  
High Salt ◽  
Macrophage Infiltration ◽  
Transient Receptor Potential Vanilloid ◽  
Plasma Urea ◽  
Renal Inflammation ◽  
High Salt Intake

High salt intake after recovery from renal ischemia-reperfusion (I/R) injury leads to hypertension and renal inflammation. This study tests the hypothesis that degeneration of transient receptor potential vanilloid type 1 (TRPV1)-positive nerves exacerbates salt-induced hypertension and renal inflammation after I/R via enhancing renal macrophage infiltration. Rats were fed a low sodium (0.4%) diet for 5 weeks after capsaicin pre-treatment (CAP, 100 mg/kg, s.c.) and renal I/R, followed by macrophage depletion with clodronate liposome (LC, 1.3 ml/kg/wk, i.v.) combined with a high sodium (4%) diet for 4 weeks. Western blot showed that CAP pretreatment further decreased renal TRPV1 levels after I/R (P<0.05), which was not affected by LC treatment. Macrophage infiltration in the renal cortex and medulla and renal proinflammatory cytokine (TNF-α and IL-1 β) levels were increased in I/R rats and further intensified in I/R+CAP rats (P<0.05), which were abolished by LC in both I/R and I/R+CAP groups. Mean arterial pressure (MAP) was elevated in I/R rats and further increased in I/R+CAP rats (P<0.05), which was prevented by LC in both I/R and I/R+CAP groups. Decreased creatinine clearance (Sham: 0.54±0.06, I/R: 0.28±0.02, I/R+CAP: 0.16±0.02, Sham+LC: 0.54±0.03, I/R+LC: 0.51±0.04, I/R+CAP+LC: 0.49±0.04 ml/min/100 gbwt, p<0.05) and increased levels of plasma urea, urinary 8-isoprostane, renal connective tissue growth factor (CTGF), and renal collage I and IV were observed in I/R rats and exacerbated in I/R+CAP rats (P<0.05), which were restored to normal levels by LC in both I/R and I/R+CAP groups. Thus, degeneration of TRPV1-positive nerves aggravates hypertension and renal inflammation and fibrosis induced by I/R and high salt intake, possibly via enhancing renal macrophage infiltration and function. These data suggest that activation of TRPV1 after renal injury conveys renal protection against inflammation and fibrosis via inhibiting macrophage infiltration.

Abstract 383: Hypertensive and Renal Injury Responses to Angiotensin II and High Salt Intake in Mice Lacking the Gene for Interleukin-10

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Purnima Singh ◽  
Alexander Castillo ◽  
Dewan S Majid
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Salt Intake ◽  
Gene Knockout ◽  
Interleukin 10 ◽  
Renal Tissue ◽  
Protective Role ◽  
High Salt ◽  
High Salt Intake ◽  
Tnf Α

Endogenous interleukin-10 (IL-10) exerts immune down-regulating action on the generation of tumor necrosis factor-alpha (TNF-α). The present study examined the hypothesis that IL-10 plays a protective role in hypertension and renal injury induced by angiotensin II (AngII) and high salt (HS) diet by minimizing TNF-α production. Systemic blood pressure (BP; monitored by implanted radio-telemetry), TNF-α level in plasma and in the kidney (by ELISA) as well as renal injury (glomerulosclerosis, GS by PAS staining and renal interstitial fibrosis, RIF by Trichrome staining) responses to chronic infusion of AngII (400 ng/min; osmotic minipump) for 2 wks were evaluated in wild-type (WT; n=11) and IL-10 gene knockout mice (KO; n=11) which were fed either normal (NS; 0.03% NaCl, n=5) or HS (4% NaCl; n=6) diets. On the last day of the experiment, a 24 hr urine collection was made using metabolic cages prior to sacrificing the mice for the collection of plasma and renal tissue samples. The mean baseline BP in KO was lower (104±3 vs 116±4 mmHg) than that in WT. Increase in BP in AngII+HS treated KO was lower (Δ 20±5 vs Δ 39±2 mmHg) than that in WT but similar in AngII+NS treated KO and WT (Δ 40±3 vs Δ 47±7 mmHg). In AngII+HS treated WT, TNF-α was higher in plasma (69±6 vs 34±4 pg/mL) and in renal tissue (208±15 vs 95±11 pg/mg protein) compared to values in WT treated with AngII+NS. In AngII+HS treated KO, TNF-α was lower in plasma (20±3 vs 180±44 pg/mL) and in renal tissue (205±23 vs 277±23 vs pg/mg protein) compared to values in KO treated with AngII+NS. The urinary nitrate/nitrite excretion rate was higher in AngII+NS (0.56±0.25 vs 0.08±0.01 mM/24 hr) and AngII+HS (1.23±0.12 vs 0.18±0.02 mM/24 hr) treated KO compared to the correspondingly treated WT. The eNOS protein expression was higher in KO treated with AngII+NS (~2 folds) or AngII+HS (~3 folds) compared to those in treated WT. GS (24.6±1.3 vs 13.8±2.1 %) and RIF (10.6±1.1 vs 7.8±0.5 %) changes were greater in AngII+NS treated KO than those in treated WT. However, the changes were minimal in HS treated groups. In conclusion, these data demonstrate that there exists an interaction of IL-10 and eNOS activity in the regulation of TNF-α in the kidney that provides a protective role by minimizing hypertension and renal injury induced by Ang II and HS intake.

scholarly journals High Salt Intake and Stroke: Meta-analysis of the Epidemiologic Evidence

2012 ◽  
Vol 18 (8) ◽  
pp. 691-701 ◽  
Author(s):  
Xiu-Yang Li ◽  
Xian-Lei Cai ◽  
Ping-Da Bian ◽  
Liu-Ru Hu
Keyword(s):  
Salt Intake ◽  
Meta Analysis ◽  
High Salt ◽  
Epidemiologic Evidence ◽  
High Salt Intake

scholarly journals Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

2011 ◽  
Vol 209 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Karine Bibeau ◽  
Mélissa Otis ◽  
Jean St-Louis ◽  
Nicole Gallo-Payet ◽  
Michèle Brochu
Keyword(s):  
Protein Expression ◽  
Adrenal Glands ◽  
Salt Intake ◽  
High Salt ◽  
Receptor Subtypes ◽  
Mrna Levels ◽  
Female Rat ◽  
Angiotensin Ii Receptor ◽  
Intrauterine Growth ◽  
High Salt Intake

In low sodium-induced intrauterine growth restricted (IUGR) rat, foetal adrenal steroidogenesis as well as the adult renin–angiotensin–aldosterone system (RAAS) is altered. The aim of the present study was to determine the expression of cytochrome P450 aldosterone synthase (P450aldo) and of angiotensin II receptor subtypes 1 (AT1R) and 2 (AT2R) in adult adrenal glands and whether this expression could be influenced by IUGR and by high-salt intake in a sex-specific manner. After 6 weeks of 0.9% NaCl supplementation, plasma renin activity, P450aldo expression and serum aldosterone levels were decreased in all groups. In males, IUGR induced an increase in AT1R, AT2R, and P450aldo levels, without changes in morphological appearance of the zona glomerulosa (ZG). By contrast, in females, IUGR had no effect on the expression of AT1R, but increased AT2R mRNA while decreasing protein expression of AT2R and P450aldo. In males, salt intake in IUGR rats reduced both AT1R mRNA and protein, while for AT2R, mRNA levels decreased whereas protein expression increased. In females, salt intake reduced ZG size in IUGR but had no affect on AT1R or AT2R expression in either group. These results indicate that, in response to IUGR and subsequently to salt intake, P450aldo, AT1R, and AT2R levels are differentially expressed in males and females. However, despite these adrenal changes, adult IUGR rats display adequate physiological and adrenal responses to high-salt intake, via RAAS inhibition, thus suggesting that extra-adrenal factors likely compensate for ZG alterations induced by IUGR.

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