Plasma miR-150-5p in Renal Transplant Recipients with Acute Antibody-Mediated Rejection.

Background: Rejection continues to be the main cause of renal graft loss. Currently, the gold standard for diagnosis is an allograft biopsy; however, because it is time-consuming, costly, and invasive, the pursuit of novel biomarkers has gained interest. Variation in the expressions of miRNAs is currently considered a probable biomarker for the diagnosis of acute rejection. This study aimed to determine whether miR-150-5p in serum is related to microvascular damage in patients with acute antibody-mediated rejection (ABMR). Methods: A total of 27 patients who underwent renal transplantation (RT) with and without ABMR were included in the study. We performed the quantification of hsa-miR-150-5p, hsa-miR-155, hsa-miR-21, hsa-miR-126, and hsa-miR-1 in plasma by RT-qPCR. The expressions between the groups and their correlations with the histological characteristics of the patients with ABMR were also investigated. Results: miR-150-5p significantly increased in the plasma of patients with rejection (p < 0.05), and the changes in miR-150-5p were directly correlated with microvascular inflammation in the allograft biopsies. Clinical utility was determined by ROC analysis with an area under the curve of 0.873. Conclusions: Our results show that the patients with RT with ABMR exhibited increased expression of miR-150-5p compared to patients without rejection, which could have clinical consequences, as well as probable utility in the diagnosis of ABMR, and bioinformatics may help in unraveling the molecular mechanisms underlying ABMR conditions.

Antioxidant and anti-inflammatory effects of allicin in the kidney of an experimental model of metabolic syndrome.

Background: Recent studies have suggested that metabolic syndrome (MS) encompasses a group of risk factors for developing chronic kidney disease (CKD). This work aimed to evaluate the antioxidant and anti-inflammatory effects of allicin in the kidney from an experimental model of MS. Methods: Male Wistar rats (220-250 g) were used, and three experimental groups (n = 6) were formed: control (C), metabolic syndrome (MS), and MS treated with allicin (16 mg/Kg/day, gastric gavage) (MS+A). MS was considered when an increase of 20% in at least three parameters (body weight, systolic blood pressure (SBP), fasting blood glucose (FBG), or dyslipidemia) was observed compared to the C group. After the MS diagnosis, allicin was administered for 30 days. Results: Before the treatment with allicin, the MS group showed more significant body weight gain, increased SBP, and FBG, glucose intolerance, and dyslipidemia. In addition, increased markers of kidney damage in urine and blood. Moreover, the MS increased oxidative stress and inflammation in the kidney compared to group C. The allicin treatment prevented further weight gain, reduced SBP, FBG, glucose intolerance, and dyslipidemia. Also, markers of kidney damage in urine and blood were decreased. Further, the oxidative stress and inflammation were decreased in the renal cortex of the MS+A compared to the MS group. Conclusion: Allicin exerts its beneficial effects on the metabolic syndrome by considerably reducing systemic and renal inflammation as well as the oxidative stress. These effects were mediated through the Nrf2 pathway. The results suggest allicin may be a therapeutic alternative for treating kidney injury induced by the metabolic syndrome risk factors.

Allicin, an Emerging Treatment for Pulmonary Arterial Hypertension: An Experimental Study.

We assessed whether allicin, through its antihypertensive and antioxidant effects, relieves vascular remodeling, endothelial function, and oxidative stress (OS), thereby improving experimental pulmonary arterial hypertension (PAH). Allicin (16 mg/kg) was administered to rats with PAH (monocrotaline 60 mg/kg). Allicin encouraged body weight gain and survival rate, and medial wall thickness and the right ventricle (RV) hypertrophy were prevented. Also, angiotensin II concentrations in the lung (0.37 ± 0.01 vs. 0.47 ± 0.06 pmoles/mL, allicin and control, respectively) and plasma (0.57 ± 0.05 vs. 0.75 ± 0.064, allicin and control respectively) and the expressions of angiotensin-converting enzyme II and angiotensin II type 1 receptor in lung tissue were maintained at normal control levels with allicin. In PAH rats treated with allicin, nitric oxide (NO) (31.72 ± 1.22 and 51.4 ± 3.45 pmoles/mL), tetrahydrobiopterin (8.43 ± 0.33 and 10.14 ± 0.70 pmoles/mL), cyclic guanosine monophosphate (5.54 ± 0.42 and 5.64 ± 0.73 pmoles/mL), and Ang-(1-7) (0.88 ± 0.23 and 0.83 ± 0.056 pmoles/mL) concentrations increased in lung tissue and plasma, respectively. In contrast, dihydrobiopterin increase was prevented in both lung tissue and plasma (5.75 ± 0.3 and 5.64 ± 0.73 pmoles/mL); meanwhile, phosphodiesterase-5 was maintained at normal levels in lung tissue. OS in PAH was prevented with allicin through the increased expression of Nrf2 in the lung. Allicin prevented the lung response to hypoxia, preventing the overexpression of HIF-1α and VEGF. Allicin attenuated the vascular remodeling and RV hypertrophy in PAH through its effects on NO-dependent vasodilation, modulation of RAS, and amelioration of OS. Also, these effects could be associated with the modulation of HIF-1α and improved lung oxygenation. The global effects of allicin contribute to preventing endothelial dysfunction, remodeling of the pulmonary arteries, and RV hypertrophy, preventing heart failure, thus favoring survival. Although human studies are needed, the data suggest that, alone or in combination therapy, allicin may be an alternative in treating PAH if we consider that, similarly to current treatments, it improves lung vasodilation and increase survival. Allicin may be considered an option when there is a lack of efficacy, and where drug intolerance is observed, to enhance the efficacy of drugs, or when more than one pathogenic mechanism must be addressed.

Osthole Prevents Heart Damage Induced by Diet-Induced Metabolic Syndrome: Role of Fructokinase (KHK).

There is increasing evidence that either ingested or produced fructose may have a role in metabolic syndrome. While not commonly considered a criterion for metabolic syndrome, cardiac hypertrophy is often associated with metabolic syndrome, and its presence carries increased cardiovascular risk. Recently it has been shown that fructose and fructokinase C (KHK) can be induced in cardiac tissue. Here we tested whether diet-induced metabolic syndrome causes heart disease associated with increased fructose content and metabolism and whether it can be prevented with a fructokinase inhibitor (osthole). Male Wistar rats were provided a control diet (C) or high fat/sugar diet for 30 days (MS), with half of the latter group receiving osthol (MS+OT, 40 mg/kg/d). The Western diet increased fructose, uric acid, and triglyceride concentrations in cardiac tissue associated with cardiac hypertrophy, local hypoxia, oxidative stress, and increased activity and expression of KHK in cardiac tissue. Osthole reversed these effects. We conclude that the cardiac changes in metabolic syndrome involve increased fructose content and its metabolism and that blocking fructokinase can provide cardiac benefit through the inhibition of KHK with modulation of hypoxia, oxidative stress, hypertrophy, and fibrosis.

Role of Sulfur Compounds in Garlic as Potential Therapeutic Option for Inflammation and Oxidative Stress in Asthma.

Asthma is a chronic inflammatory disease in the airways with a multifactorial origin but with inflammation and oxidative stress as related pathogenic mechanisms. Garlic (Allium sativum) is a nutraceutical with different biological properties due to sulfur-containing natural compounds. Studies have shown that several compounds in garlic may have beneficial effects on cardiovascular diseases, including those related to the lungs. Therefore, it is possible to take advantage of the compounds from garlic as nutraceuticals for treating lung diseases. The objective of this article is to review the biological properties of the sulfur compounds present in garlic for the treatment of asthma, as well as the cellular mechanisms involved. Here, we discuss the potential therapeutic effects of garlic compounds in the modulation of inflammation and oxidative stress, as well as its antibiotic and antiviral activities for identifying and testing potential treatment options for asthma management.

Self-reported dietary omega-3 polyunsaturated fatty acids are associated with adipose tissue markers and glucose metabolism in apparently healthy subjects.

BACKGROUND: Plasminogen activator inhibitor 1 (PAI-1) and resistin are associated with dysfunctional adipose tissue (AT)-related metabolic complications. The role of dietary eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids in this relationship is unknown. AIM: To investigate the association of EPA and DHA with PAI-1 and resistin, as well as the role of this association on the glucose metabolism of apparently healthy subjects. SUBJECTS AND METHODS: Thirty-six healthy individuals were included. Validated food frequency questionnaires were used to analyse dietary habits. Inflammatory and glucose metabolism markers were quantified. Subcutaneous AT samples were obtained, and adipocyte number, area, and macrophage content were assessed. RESULTS: In 36 subjects aged 56 ± 8 years and with a body mass index of 26 ± 4 kg/m2, logEPA, and logDHA showed significant association with logresistin and a marginal association with PAI-1. Adipocyte number, area, and lognumber of macrophages per adipocyte significantly correlated with PAI-1 but not with logresistin. Although logEPA and logDHA were independently associated with loginsulin, loginsulin resistance, and C-Peptide, the addition of logresistin, but not of PAI-1, into the multivariable model, abolished the associations. CONCLUSIONS: EPA and DHA could modulate glucose metabolism across AT functional states. Our data indicate that this association is independent of other metabolic risk factors.

Mecanismos moleculares de los efectos benéficos de la alicina sobre la enfermedad cardiovascular / Molecular mechanisms of the beneficial effects of allicin on cardiovascular disease

Resumen Las enfermedades cardiovasculares (ECV) comprenden un grupo de enfermedades cuyo denominador común es la afectación de vasos sanguíneos, corazón y ritmo cardiaco. El tratamiento de las ECV representa costos muy altos para los sistemas de salud y está enfocado en el control de los factores de riesgo. A pesar de existir una gran variedad de fármacos para el tratamiento de las ECV, estas continúan siendo las principales causas de mortalidad, posiblemente debido a que su origen es multifactorial y por ello se requiere de más de un fármaco. En este contexto, la alicina, un compuesto derivado del ajo, ha mostrado regular la expresión de vías de señalización y factores de riesgo asociados a la progresión de las ECV. Por ello el objetivo del presente trabajo es revisar los mecanismos celulares y moleculares por medio de los cuales la alicina ejerce sus efectos terapéuticos y describir las evidencias científicas del porqué la alicina podría representar un potencial candidato para coadyuvar en el tratamiento de las ECV.

Abstract Cardiovascular diseases (CVD) include a group of diseases whose common denominator is the affection of the blood vessels, heart, and heart rate. The treatment of CVD represents high costs to the health systems and is focused on the control of risk factors. Despite the existence of a great variety of treatments of the CVD, these continue as the main cause of mortality mainly due to the multifactorial origin, and therefore more than one drug is required. In this context, allicin, a compound derived from garlic, has shown regulate the expression of signaling pathways and risk factors associated with the progression of CVD. Therefore, the objective of this work is to review the cellular and molecular mechanisms through which allicin exert its therapeutic effects and to describe the scientific evidences why allicin represents a potential candidate to assist in the treatment of CVD.

Cellular Mechanisms Underlying the Cardioprotective Role of Allicin on Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are a group of diseases in which the common denominator is the affection of blood vessels, heart tissue, and heart rhythm. The genesis of CVD is complex and multifactorial; therefore, approaches are often based on multidisciplinary management and more than one drug is used to achieve the optimal control of risk factors (dyslipidemia, hypertension, hypertrophy, oxidative stress, endothelial dysfunction, inflammation). In this context, allicin, a sulfur compound naturally derived from garlic, has shown beneficial effects on several cardiovascular risk factors through the modulation of cellular mechanisms and signaling pathways. Effective pharmacological treatments for CVD or its risk factors have not been developed or are unknown in clinical practice. Thus, this work aimed to review the cellular mechanisms through which allicin exerts its therapeutic effects and to show why it could be a therapeutic option for the prevention or treatment of CVD and its risk factors.

Mecanismos moleculares de los efectos benéficos de la alicina sobre la enfermedad cardiovascular.

Las enfermedades cardiovasculares (ECV) comprenden un grupo de enfermedades cuyo denominador común es la afectación de vasos sanguíneos, corazón y ritmo cardiaco. El tratamiento de las ECV representa costos muy altos para los sistemas de salud y está enfocado en el control de los factores de riesgo. A pesar de existir una gran variedad de fármacos para el tratamiento de las ECV, estas continúan siendo las principales causas de mortalidad, posiblemente debido a que su origen es multifactorial y por ello se requiere de más de un fármaco. En este contexto, la alicina, un compuesto derivado del ajo, ha mostrado regular la expresión de vías de señalización y factores de riesgo asociados a la progresión de las ECV. Por ello el objetivo del presente trabajo es revisar los mecanismos celulares y moleculares por medio de los cuales la alicina ejerce sus efectos terapéuticos y describir las evidencias científicas del porqué la alicina podría representar un potencial candidato para coadyuvar en el tratamiento de las ECV.Cardiovascular diseases (CVD) include a group of diseases whose common denominator is the affection of the blood vessels, heart, and heart rate. The treatment of CVD represents high costs to the health systems and is focused on the control of risk factors. Despite the existence of a great variety of treatments of the CVD, these continue as the main cause of mortality mainly due to the multifactorial origin, and therefore more than one drug is required. In this context, allicin, a compound derived from garlic, has shown regulate the expression of signaling pathways and risk factors associated with the progression of CVD. Therefore, the objective of this work is to review the cellular and molecular mechanisms through which allicin exert its therapeutic effects and to describe the scientific evidences why allicin represents a potential candidate to assist in the treatment of CVD.

Current Hydration Habits: The Disregarded Factor for the Development of Renal and Cardiometabolic Diseases.

Improper hydration habits are commonly disregarded as a risk factor for the development of chronic diseases. Consuming an intake of water below recommendations (underhydration) in addition to the substitution of sugar-sweetened beverages (SSB) for water are habits deeply ingrained in several countries. This behavior is due to voluntary and involuntary dehydration; and because young children are exposed to SSB, the preference for a sweet taste is profoundly implanted in the brain. Underhydration and SSB intake lead to mild hyperosmolarity, which stimulates biologic processes, such as the stimulation of vasopressin and the polyol-fructose pathway, which restore osmolarity to normal but at the expense of the continued activation of these biological systems. Unfortunately, chronic activation of the vasopressin and polyol-fructose pathways has been shown to mediate many diseases, such as obesity, diabetes, metabolic syndrome, chronic kidney disease, and cardiovascular disease. It is therefore urgent that we encourage educational and promotional campaigns that promote the evaluation of personal hydration status, a greater intake of potable water, and a reduction or complete halting of the drinking of SSB.

Uric acid is associated with morpho-functional adipose tissue markers in apparently healthy subjects.

BACKGROUND: Studies have focused on the search of novel biomarkers that allow to easily identify dysfunctional adipose tissue (AT). Uric acid (UA) could be produced and reabsorbed by AT. It has been suggested that the increases of UA concentrations participates in AT dysfunction. We investigated the association of UA with morpho-functional adipose tissue markers in apparently healthy subjects. METHODS: Forty apparently healthy individuals were included. Dietary habits and anthropometrical features were evaluated. Circulating concentrations of UA, adiponectin, leptin, and plasminogen activator inhibitor-1 (PAI-1) were quantified. Periumbilical subcutaneous AT samples were obtained and adipocyte number, adipocyte area, and macrophages content were assessed. RESULTS: The present study included 40 healthy subjects (67% women) with an average age of 57 ± 9 y, BMI of 26 ± 4 (kg/m2). UA showed a significant association with the number and mean area of adipocytes, macrophages number, adiponectin, and PAI-1. Although UA was independently associated with the number and mean area of adipocytes, macrophages number, adiponectin into the adjusted multivariable model. CONCLUSION: UA concentrations are associated with morpho-functional adipose tissue markers. Our results underscore the importance of UA as one earlier instigator of adipose tissue dysfunction in subjects without metabolic abnormalities.

Extracellular Vesicles in Redox Signaling and Metabolic Regulation in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a world health problem increasing dramatically. The onset of CKD is driven by several mechanisms; among them, metabolic reprogramming and changes in redox signaling play critical roles in the advancement of inflammation and the subsequent fibrosis, common pathologies observed in all forms of CKD. Extracellular vesicles (EVs) are cell-derived membrane packages strongly associated with cell-cell communication since they transfer several biomolecules that serve as mediators in redox signaling and metabolic reprogramming in the recipient cells. Recent studies suggest that EVs, especially exosomes, the smallest subtype of EVs, play a fundamental role in spreading renal injury in CKD. Therefore, this review summarizes the current information about EVs and their cargos' participation in metabolic reprogramming and mitochondrial impairment in CKD and their role in redox signaling changes. Finally, we analyze the effects of these EV-induced changes in the amplification of inflammatory and fibrotic processes in the progression of CKD. Furthermore, the data suggest that the identification of the signaling pathways involved in the release of EVs and their cargo under pathological renal conditions can allow the identification of new possible targets of injury spread, with the goal of preventing CKD progression.

A ketogenic diet attenuates acute and chronic ischemic kidney injury and reduces markers of oxidative stress and inflammation.

BACKGROUND: Ischemic kidney injury is a common clinical condition resulting from transient interruption of the kidney's normal blood flow, leading to oxidative stress, inflammation, and kidney dysfunction. The ketogenic diet (KD), a low-carbohydrate, high-fat diet that stimulates endogenous ketone body production, has potent antioxidant and anti-inflammatory effects in distinct tissues and might thus protect the kidney against ischemia and reperfusion (IR) injury. MAIN METHODS: Male Wistar rats were fed a KD or a control diet (CD) for three days before analyzing metabolic parameters or testing nephroprotection. We used two different models of kidney IR injury and conducted biochemical, histological, and Western blot analyses at 24 h and two weeks after surgery. KEY FINDINGS: Acute KD feeding caused protein acetylation, liver AMPK activation, and increased resistance to IR-induced kidney injury. At 24 h after IR, rats on KD presented reduced tubular damage and improved kidney functioning compared to rats fed with a CD. KD attenuated oxidative damage (protein nitration, 4-HNE adducts, and 8-OHdG), increased antioxidant defenses (GPx and SOD activity), and reduced inflammatory intermediates (IL6, TNFα, MCP1), p50 NF-κB expression, and cellular infiltration. Also, KD prevented interstitial fibrosis development at two weeks, up-regulation of HSP70, and chronic Klotho deficiency. SIGNIFICANCE: Our findings demonstrate for the first time that short-term KD increases tolerance to experimental kidney ischemia, opening the opportunity for future therapeutic exploration of a dietary preconditioning strategy to convey kidney protection in the clinic.

Cold exposure aggravates pulmonary arterial hypertension through increased miR-146a-5p, miR-155-5p and cytokines TNF-α, IL-1ß, and IL-6.

BACKGROUND: Cold temperatures can aggravate pulmonary diseases and promote pulmonary arterial hypertension (PAH); however, the underlying mechanism has not been fully explored. AIM: To explore the effect of chronic cold exposure on the production of inflammatory cytokines and microRNAs (miRNAs) in a monocrotaline (MCT)-induced PAH model. METHODS: Male Sprague Dawley rats were divided into a Control (23.5 ± 2 °C), Cold (5.0 ± 1 °C for ten days), MCT (60 mg/kg body weight i.p.), and MCT + Cold (ten days of cold exposure after 3 weeks of MCT injection). Hemodynamic parameters, right ventricle (RV) hypertrophy, and pulmonary arterial medial wall thickness were determined. IL-1ß, IL-6, and TNF-α levels were determined using western blotting. miR-21-5p and -3p, miR-146a-5p and -3p, and miR-155-5p and -3p and plasma extracellular vesicles (EVs) and mRNA expression of Cd68, Cd163, Bmpr2, Smad5, Tgfbr2, and Smad3 were determined using RT-qPCR. RESULTS: The MCT + Cold group had aggravated RV hypertrophy hemodynamic parameters, and pulmonary arterial medial wall thickness. In lungs of the MCT + Cold, group the protein levels of TNF-α, IL-1ß, and IL-6 were higher than those in the MCT group. The mRNA expression of Cd68 and Cd163 were higher in the MCT + Cold group. miR-146a-5p and miR-155-5p levels were higher in the plasma EVs and lungs of the MCT + Cold group. Cold exposure promoted a greater decrease in miR-21-5p, Bmpr2, Smad5, Tgfbr2, and Smad3 mRNA expression in lungs of the MCT + Cold group. CONCLUSION: Cold exposure aggravates MCT-induced PAH with an increase in inflammatory marker and miRNA levels in the plasma EVs and lungs.

Anti-Inflammatory Effect of Allicin Associated with Fibrosis in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling. Recent evidence supports that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Recent studies have shown that garlic extract has protective effects in PAH, but the precise role of allicin, a compound derived from garlic, is unknown. Thus, we used allicin to evaluate its effects on inflammation and fibrosis in PAH. Male Wistar rats were divided into three groups: control (CON), monocrotaline (60 mg/kg) (MCT), and MCT plus allicin (16 mg/kg/oral gavage) (MCT + A). Right ventricle (RV) hypertrophy and pulmonary arterial medial wall thickness were determined. IL-1ß, IL-6, TNF-α, NFκB p65, Iκß, TGF-ß, and α-SMA were determined by Western blot analysis. In addition, TNF-α and TGF-ß were determined by immunohistochemistry, and miR-21-5p and mRNA expressions of Cd68, Bmpr2, and Smad5 were determined by RT-qPCR. Results: Allicin prevented increases in vessel wall thickness due to TNF-α, IL-6, IL-1ß, and Cd68 in the lung. In addition, TGF-ß, α-SMA, and fibrosis were lower in the MCT + A group compared with the MCT group. In the RV, allicin prevented increases in TNF-α, IL-6, and TGF-ß. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH.

High fructose exposure modifies the amount of adipocyte-secreted microRNAs into extracellular vesicles in supernatants and plasma.

BACKGROUND: High fructose exposure induces metabolic and endocrine responses in adipose tissue. Recent evidence suggests that microRNAs in extracellular vesicles are endocrine signals secreted by adipocytes. Fructose exposure on the secretion of microRNA by tissues and cells is poorly studied. Thus, the aim of this study was to evaluate the effect of fructose exposure on the secretion of selected microRNAs in extracellular vesicles from 3T3-L1 cells and plasma from Wistar rats. METHODS: 3T3-L1 cells were exposed to 550 µM of fructose or standard media for four days, microRNAs levels were determined in extracellular vesicles of supernatants and cells by RT-qPCR. Wistar rats were exposed to either 20% fructose drink or tap water for eight weeks, microRNAs levels were determined in extracellular vesicles of plasma and adipose tissue by RT-qPCR. RESULTS: This study showed that fructose exposure increased the total number of extracellular vesicles released by 3T3-L1 cells (p = 0.0001). The levels of miR-143-5p were increased in extracellular vesicles of 3T3-L1 cells exposed to fructose (p = 0.0286), whereas miR-223-3p levels were reduced (p = 0.0286). Moreover, in plasma-derived extracellular vesicles, miR-143-5p was higher in fructose-fed rats (p = 0.001), whereas miR-223-3p (p = 0.022), miR-342-3p (p = 0.0011), miR-140-5p (p = 0.0129) and miR-146b-5p (p = 0.0245) were lower. CONCLUSION: Fructose exposure modifies the levels of microRNAs in extracellular vesicles in vitro and in vivo. In particular, fructose exposure increases miR-143-5p, while decreases miR-223-3p and miR-342-3p.

Dysfunctional adiposity index as a marker of adipose tissue morpho-functional abnormalities and metabolic disorders in apparently healthy subjects.

Compared to body mass index, waist circumference (WC), and adiposity measurements, adipose tissue (AT) morpho-functionality evaluations are better predictors of cardiometabolic abnormalities (CA). The present study establishes a dysfunctional adiposity index (DAI) as an early marker of CA based on adipocytes morpho-functional abnormalities. DAI was established in 340 subjects without cardiovascular risk factors selected from a cross-sectional study (n=1600). Then, DAI was calculated in 36 healthy subjects who underwent subcutaneous AT biopsy. The correlation of DAI with adipocyte morphology (size/number) and functionality (adiponectin/leptin ratio) was analyzed. The DAI cut-off point was identified and its independent association with CA was determined in 1418 subjects from the cross-sectional study. The constant parameters to calculate the DAI were [WC/[22.79+[2.68*BMI]]]*[triglycerides (TG, mmol/L)/1.37]*[1.19/high density lipoprotein-cholesterol (HDL-C, mmol/L)] for males, and [WC/[24.02+[2.37*BMI]]]*[TG(mmol/L)/1.32]*[1.43/HDL-C(mmol/L)] for females. DAI correlated with adipocytes mean area, adipocyte number and adiponectin/leptin ratio. DAI ≥1.065 was independently associated with diabetes, non-alcoholic fatty liver disease, subclinical atherosclerosis, and hypertension. The present study highlights that DAI is associated with early CA independently of adiposity and other risk factors. Since DAI is obtained using accessible parameters, it can be easily incorporated into clinical practice for early identification of AT abnormalities in apparently healthy subjects.

Osthol Ameliorates Kidney Damage and Metabolic Syndrome Induced by a High-Fat/High-Sugar Diet.

Excessive intake of fructose results in metabolic syndrome (MS) and kidney damage, partly mediated by its metabolism by fructokinase-C or ketohexokinase-C (KHK-C). Osthol has antioxidant properties, is capable of regulating adipogenesis, and inhibits KHK-C activity. Here, we examined the potential protective role of osthol in the development of kidney disease induced by a Western (high-fat/high-sugar) diet. Control rats fed with a high-fat/high-sugar diet were compared with two groups that also received two different doses of osthol (30 mg/kg/d or 40 mg/kg/d body weight BW). A fourth group served as a normal control and received regular chow. At the end of the follow-up, kidney function, metabolic markers, oxidative stress, and lipogenic enzymes were evaluated. The Western diet induced MS (hypertension, hyperglycemia, hypertriglyceridemia, obesity, hyperuricemia), a fall in the glomerular filtration rate, renal tubular damage, and increased oxidative stress in the kidney cortex, with increased expression of lipogenic enzymes and increased kidney KHK expression. Osthol treatment prevented the development of MS and ameliorated kidney damage by inhibiting KHK activity, preventing oxidative stress via nuclear factor erythroid 2-related factor (Nrf2) activation, and reducing renal lipotoxicity. These data suggest that the nutraceutical osthol might be an ancillary therapy to slow the progression of MS and kidney damage induced by a Western diet.

Fluid Intake Restriction Concomitant to Sweetened Beverages Hydration Induce Kidney Damage.

Currently, there is the paradox of low water intake but increased intake of sugar-sweetened beverages (SB) in several populations; those habits are associated with an increased prevalence of metabolic derangements and greater chronic disease mortality. Persistent heat dehydration and increased SB intake stimulate the continued release of vasopressin and overactivation of the polyol-fructokinase pathway, synergizing each other, an effect partially mediated by oxidative stress. The objective of the present study was to evaluate whether water restriction concurrent with SB hydration can cause renal damage by stimulating similar pathways as heat dehydration. Three groups of male Wistar rats (n = 6) were fluid restricted; from 10 am to 12 pm animals could rehydrate with tap water (W), or sweetened beverages, one prepared with 11% of a fructose-glucose combination (SB), or with the noncaloric edulcorant stevia (ST). A normal control group of healthy rats was also studied. The animals were followed for 4 weeks. Markers of dehydration and renal damage were evaluated at the end of the study. Fluid restriction and water hydration mildly increased urine osmolality and induced a 15% fall in CrCl while increased the markers of tubular damage by NAG and KIM-1. Such changes were in association with a mild overexpression of V1a and V2 renal receptors, polyol fructokinase pathway overactivation, and increased renal oxidative stress with reduced expression of antioxidant enzymes. Hydration with SB significantly amplified those alterations, while in stevia hydrated rats, the changes were similar to the ones observed in water hydrated rats. These data suggest that current habits of hydration could be a risk factor in developing kidney damage.

Restricted Water Intake and Hydration with Fructose-Containing Beverages during Infancy Predispose to Aggravate an Acute Renal Ischemic Insult in Adolescent Rats.

We aimed to investigate the effects of chronic fluid restriction and hydration with a sweetened beverage (SB) in rats from weaning until adolescence, in a posterior acute kidney injury (AKI) event induced by ischemia-reperfusion (I/R). We followed 5 groups of weaning rats: control group (C); two groups with 22 h/day fluid restriction, a group hydrated for two hours with water (-W) and a group hydrated with SB; one group receiving SB ad libitum all day (+SB); and one group in which water consumption was increased using a gel diet. The rats that reached adolescence were submitted to I/R. Fluid restriction and/or SB hydration induced mild renal alterations that were significantly accentuated in the -SB group and resulted in worse outcomes after I/R-induced AKI that resulted in a catastrophic fall in creatinine clearance and diffuse acute tubular necrosis. In summary, low tap water intakes, as well as SB intake in infancy, prompt kidney worse outcomes in a later event of AKI during adolescence and both insults magnify kidney damage. Studies on hydration habits in children are recommended to disclose the potentially harmful effects that those behavioral patterns might carry to future renal health.