Alamandine alleviates hypertension and renal damage via oxidative-stress attenuation in Dahl rats

Alamandine (Ala) is a novel member of the renin–angiotensin-system (RAS) family. The present study aimed to explore the effects of Ala on hypertension and renal damage of Dahl salt-sensitive (SS) rats high-salt diet-induced, and the mechanisms of Ala on renal-damage alleviation. Dahl rats were fed with high-salt diets to induce hypertension and renal damage in vivo, and HK-2 cells were treated with sodium chloride (NaCl) to induce renal injury in vitro. Ala administration alleviated the high-salt diet-induced hypertension, renal dysfunction, and renal fibrosis and apoptosis in Dahl SS rats. The HK-2 cells’ damage, and the increases in the levels of cleaved (c)-caspase3, c-caspase8, and c-poly(ADP-ribose) polymerase (PARP) induced by NaCl were inhibited by Ala. Ala attenuated the NaCl-induced oxidative stress in the kidney and HK-2 cells. DETC, an inhibitor of SOD, reversed the inhibitory effect of Ala on the apoptosis of HK-2 cells induced by NaCl. The NaCl-induced increase in the PKC level was suppressed by Ala in HK-2 cells. Notably, PKC overexpression reversed the moderating effects of Ala on the NaCl-induced apoptosis of HK-2 cells. These results show that Ala alleviates high-salt diet-induced hypertension and renal dysfunction. Ala attenuates the renal damage via inhibiting the PKC/reactive oxygen species (ROS) signaling pathway, thereby suppressing the apoptosis in renal tubular cells.

HIGH SALT INTAKE IMPLICATIONS AS RISK FACTOR FOR HYPERTENSION AND COMPARISON OF THREE SALT ESTIMATION METHODS- FINDINGS FROM ISLAMABAD, PAKISTAN

Objectives: The study was designed to estimate daily salt intake, its discretionary use in healthy individuals and to validate three common methods for salt estimation in Pakistani population. Methodology: Information on demography and discretionary salt use was collected from healthy adults (>18 years) along with a blood sample, spot and 24 hour urine samples. Sodium, chloride, potassium levels and serum creatinine were measured using standard methods. For daily salt estimation, three common methods i.e. INTERSALT, Tanaka and Kawasaki were validated for their applicability in local settings. Results: Overall 24 h sodium excretion was 158 mmol/l indicating intake of 8.64 (±4.43) grams salt per day which was significantly associated with male gender (p. <0.004) and adding salt during cooking (p. <0.0001). Most (73%) of the participants know about hazardous effects of high salt intake, however, only 25% consider important to lower salt intake. None of three methods i.e. INTERSALT (bias: -19.64; CCC -0.79), Tanaka (bias: 167.35; CCC -0.37) and Kawasaki (bias: -42.49, CCC -0.79) showed any agreement between measured and estimated 24 hour sodium. Conclusion: Daily intake of salt was high which increases the risk for hypertension. Comparison of methods for estimation revealed that none of the three methods could be used for estimating daily intake of salt in local settings of Pakistan.

Parkia biglobosa aqueous extract ameliorates risk markers of cardiometabolic diseases in spironolactone treated and high-salt fed Sprague-Dawley male rat

Background: The numbers of people with salt-sensitive hypertension and cardiometabolic diseases (CMD) are increasing due to high-salt diet (HSD) consumption globally. Parkia biglobosa (PB), an African locust bean tree, has been reported to have several cardiovascular protective properties but its ameliorative effects on CMD are scarcely reported. Therefore, this study aimed at investigating the effects of PB stem bark aqueous extract on some risk markers of CMD in weanling male rats subjected to HSD and Spironolactone (Sp) treatment.Twenty-five weanling male rats (95-105 g) were divided into 5 groups: Group 1 (Control); Group 2 (untreated HSD) fed on normal chow and HSD (8% NaCl); Group 3 (HSD+Sp); Group 4 (HSD+PB); Group 5 (HSD+Sp+PB) fed on HSD (8% NaCl) and received either 80 mg/kg of Sp or 400 mg/kg of PB and both as treatment, respectively. After 6 weeks of treatment, blood samples and heart were collected from each animal for biochemical analysis.Results: Administration of both PB and Sp or only PB, significantly decreased the plasma or cardiac adenosine deaminase, xanthine oxidase, C-reactive protein, lipids (except high density lipoprotein), uric acid, sodium, and potassium concentrations. Contrarily, the plasma as well as cardiac nitric oxide and endothelial nitric oxide synthase increased significantly by the same treatment.Conclusion: Parkia biglobosa or its administration with Spironolactone ameliorates associated-risk markers of cardiometabolic disease which are triggered by high salt diet.

Increased Salt Intake Decreases Diet-Induced Thermogenesis in Healthy Volunteers: A Randomized Placebo-Controlled Study

High salt intake ranks among the most important risk factors for noncommunicable diseases. Western diets, which are typically high in salt, are associated with a high prevalence of obesity. High salt is thought to be a potential risk factor for obesity independent of energy intake, although the underlying mechanisms are insufficiently understood. A high salt diet could influence energy expenditure (EE), specifically diet-induced thermogenesis (DIT), which accounts for about 10% of total EE. We aimed to investigate the influence of high salt on DIT. In a randomized, double-blind, placebo-controlled, parallel-group study, 40 healthy subjects received either 6 g/d salt (NaCl) or placebo in capsules over 2 weeks. Before and after the intervention, resting EE, DIT, body composition, food intake, 24 h urine analysis, and blood pressure were obtained. EE was measured by indirect calorimetry after a 12 h overnight fast and a standardized 440 kcal meal. Thirty-eight subjects completed the study. Salt intake from foods was 6 g/d in both groups, resulting in a total salt intake of 12 g/d in the salt group and 6 g/d in the placebo group. Urine sodium increased by 2.29 g/d (p < 0.0001) in the salt group, indicating overall compliance. The change in DIT differed significantly between groups (placebo vs. salt, p = 0.023). DIT decreased by 1.3% in the salt group (p = 0.048), but increased by 0.6% in the placebo group (NS). Substrate oxidation indicated by respiratory exchange ratio, body composition, resting blood pressure, fluid intake, hydration, and urine volume did not change significantly in either group. A moderate short-term increase in salt intake decreased DIT after a standardized meal. This effect could at least partially contribute to the observed weight gain in populations consuming a Western diet high in salt.

Microcirculatory and glycocalyx properties are lowered by high salt diet but augmented by western diet in genetically heterogeneous mice

Many individuals in industrialized societies consume a high salt, western diet, however, the effects of this diet on microcirculatory properties and glycocalyx barrier function are unknown. Young genetically heterogeneous male and female mice underwent 12 weeks of normal chow diet (NC), NC diet with 4% salt (NC4%), western diet (WD), or WD with 4% salt (WD4%). Microcirculatory properties and glycocalyx barrier function were evaluated in the mesenteric microcirculation using an intravital microscope equipped with an automated capture and analysis system. Total microvascular density summed across 4-25 μm microvessel segment diameters was lower in NC4% compared to NC and WD (P<0.05). Perfused boundary region (PBR), a marker of glycocalyx barrier function, averaged across 4-25 μm microvessel segment diameters was similar between NC and NC4%, as well as between WD and WD4% (P>0.05). PBR was lower in WD and WD4% compared to NC and NC4% (P<0.05), indicating augmented glycocalyx barrier function in WD and WD4%. There were strong, inverse relationships between PBR and adiposity and blood glucose (r=-0.44 to -0.61, P<0.05). In summary, NC4% induces deleterious effects on microvascular density, whereas WD augments glycocalyx barrier function. Interestingly, the combination of high salt, western diet in WD4% resulted in lower total microvascular density like NC4% and augmented glycocalyx barrier function like WD. These data suggest distinct microcirculatory adaptations to high salt and western diets that coincide when these diets are combined in young genetically heterogeneous male and female mice.

The prevalence and habit-associated risk factors of gastroesophageal reflux disease among fishermen in Indonesia

Background. This study was aimed to investigate the prevalence and habit-associated risk factors of gastroesophageal reflux disease (GERD) among fishermen.Methods. A cross-sectional study was conducted among 168 adult fishermen in Cirebon Regency, West Java, Indonesia. A self-administered questionnaire was given. The questionnaire consisted of demographic characteristics and validated GERD questionnaire (GERDQ) in Indonesian language. Data were analyzed using descriptive statistics and chi-square test. The study has been approved by the Medical Research Ethic Comiittee.Results. The medan age of the participants was 39.0 (24-86) years old. They were predominanty (60.7%) female. The prevalence of GERD was 22.6%. According to bivariate analysis, there was association between smoking (PR 1.181; 95%CI 1.013-1.377;p 0.041), high-salt intake (PR 2.419;95%CI 1.079-5.424; p 0.029), herb consumption (PR 3.068; 95%CI 1.307-7.200; p 0.008), poor hand hygiene (PR 3.202; 95%ci 1.445-7.095; p 0.003), and non-steroidal anti-inflammatory drug (NSAID) consumption (PR 3.062; 95%CI 1.446-6.488; p 0.00) with GERD. Tea consumption, coffee consumption, and raw vegetable eating were not associated with GERD.Conclusions This population-based study showed that the prevalence of GERD among fishermen in Indonesia is high. Habits associated with GERD in this study were smoking, high-salt intake, herb consumption poor, hand hygiene,

High-Salt Diet in the Pre- and Postweaning Periods Leads to Amygdala Oxidative Stress and Changes in Locomotion and Anxiety-Like Behaviors of Male Wistar Rats

High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)—offspring of standard diet fed dams who received a standard diet after weaning (n = 9–11), control-HS (C-HS)—offspring of standard diet fed dams who received a HS diet after weaning (n = 9–11), HS-C—offspring of HS diet fed dams who received a standard diet after weaning (n = 9–11), and HS-HS—offspring of HS diet fed dams who received a HS diet after weaning (n = 9–11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.

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

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.