The widespread consumption of monosodium glutamate (MSG) is linked to serious health threats which would be magnified when accompanied by high-fat/high-sugar diets. This study investigated the metabolic and hepatic perturbations of adding MSG to high fat/fructose diet in adult male rats and the possible ameliorative effects of calcitriol, and candesartan. Rats were fed high-fat/fructose diet plus sodium chloride (FF/NaCl) or MSG (FF/MSG) for 18 weeks, and were treated with either drug daily for the last 10 weeks. MSG exacerbated dyslipidemia, glucose intolerance, hypertension, and hepatic expression of mGLuR5 and ketohexoknase compared to NaCl. Both FF/NaCl and FF/MSG impaired hepatic insulin signaling biomarkers IRS-1 and Akt but MSG enhanced FoxO1 expression compared to NaCl. Furthermore, MSG exacerbated MASH hallmarks; steatosis, inflammation, and fibrosis. Both drugs mitigated most of the FF/MSG-induced metabolic and hepatic manifestations by downregulating mGLuR5, hetohexokinase, and FoxO1, beside their antioxidant, antiinflammatory, and antifibrotic effects. Calcitriol, and candesartan protect against MSG-induced hepatic derangements through downregulation of hepatic mGluR5, KHK, and FoxO1 expression in addition to their well-known anti-inflammatory and antifibrotic effects.

There are a substantial number of patients developing heart failure after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), even though AS has been successfully treated. The purpose of this randomised controlled trial was to determine whether the addition of an angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan, is superior to conventional medications in lowering N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients undergoing TAVI for AS.

Effective strategies are required to address food safety issues related to the illegal addition of antihypertensive drugs to food and claims of antihypertensive function. In this study, a novel ultra-high performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of three antihypertensive drugs (azilsartan, candesartan cilexetil, and lacidipine) in 12 food matrices (pressed candies, solid beverages, alternative teas, tea drinks, biscuits, jellies, mixed liquors, oral liquids, medicinal teas, tablets, hard capsules, and soft capsules). Initially, mass spectrometry parameters, such as the collision energies of the three antihypertensive drugs, were optimized. Subsequently, the response intensities and chromatographic separation conditions of the three drugs in different mobile phases were compared. In addition, to enhance the recoveries, various extraction solvents and purification methods, including solid-phase extraction (SPE) columns and the QuEChERS technique, were investigated. In the developed method, sample determination involved three steps. First, the sample was extracted using 0.2% (v/v) formic acid in acetonitrile and then filtered using high-speed centrifugation, in addition, the extracted solution of alternative tea and medicinal tea was purified using the QuEChERS technique. Second, the supernatant was diluted with water, and filtered through a 0.22 μm polytetrafluoroethylene (PTFE) membrane. Finally, the analytes were separated on an Agilent Eclipse Plus RRHD C18 column (50 mm×2.1 mm, 1.8 μm) using a 5 mmol/L ammonium formate aqueous solution and acetonitrile as the mobile phases under gradient elution conditions and then detected using UHPLC-MS/MS with positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. Methodological validation showed good linear relationships for all three antihypertensive drugs in the investigated concentration ranges, with correlation coefficients (r[2]) greater than 0.996. The limit of detection (LOD) and limit of quantification (LOQ) of lacidipine were 0.02 mg/kg and 0.04 mg/kg, respectively, whereas those of the other two drugs were 0.01 mg/kg and 0.02 mg/kg, respectively. In the 12 food matrices, the average recoveries of the drugs ranged from 86.6% to 107.5% with relative standard deviations (RSDs) of 1.1%-10.9% (n=6) at low, medium, and high spiked levels. Furthermore, this method was successfully applied to the analysis of real food samples. Overall, the newly developed method is simple, rapid, sensitive, accurate, and suitable for the qualitative and quantitative determination of antihypertensive drugs in different food matrices. This work could provide technical support for food safety agencies in implementing measures against the illegal addition of antihypertensive drugs to food.

In this study, we investigated the uptake and metabolization of four drugs (plus the associated prodrugs) from the sartan family by eight edible plants. Growing the plants hydroponically in a medium containing the respective drug, more than 40 phases I and II metabolites derived from the four sartan drugs could be tentatively identified. To demonstrate the suitability of the proposed analytical approach for actual environmental samples, garden cress (Lepidium sativum) selected as a model plant was grown in water drawn from the effluent of two local wastewater treatment plants. Thereby, three of the sartans, namely, olmesartan, candesartan, and valsartan, could be found in the plant extracts at concentrations of 3.1, 10.4, and 14.4 ng g[-1], respectively. Additionally, for candesartan and valsartan, a glycosylated transformation product could be detected. In order to extend the present (targeted) workflow also toward the analysis of unknown transformation products (i.e., those not listed in the custom-made database used for this research), a nontargeted approach for the analysis of plant extracts with respect to the presence of drug-related metabolites was developed. Comparison of the targeted and the nontargeted workflows led to the finding of two additional, so far unidentified, transformation products originating from azilsartan.

A low-salt diet may activate the renin-angiotensin-aldosterone system (RAAS) and is often applied simultaneously with RAAS inhibitors, especially for treatment of proteinuric nephritis. To explore the effect of a low-salt diet combined with angiotensin receptor blockers (ARB) on kidney function, the proteinuric nephritis model was induced by single intravenous injection of doxorubicin, and then the SD rats were administrated with candesartan intraperitoneal injection and fed with different salt diets. Rats with low-salt plus candesartan, not either alone, experienced acute kidney injury (AKI) at day 7 and could not self-restore when extending the experiment time from 7 days to 21 days, unless switching low-salt to normal-salt. Among three nitric oxide synthetases (NOS), endothelial NOS (eNOS) was obviously elevated and PI3K-Akt-eNOS signal pathway was activated. NG-Nitro-L-Arginine Methyl Ester (L-NAME), an eNOS inhibitor, reversed the decreased blood pressure and recovered the kidney dysfunction induced by low-salt with candesartan. The increased TUNEL-positive cells, Bax/Bcl-2 and cleaved-caspase3 protein abundance was ameliorated by L-NAME in vivo. In vitro, sodium nitroprusside, a nitric oxide donor, can also increase Bax/Bcl-2 and cleaved-caspase3 protein level in HK-2 cell. Thus, low-salt diet combined with candesartan in nephritis rats led to AKI, and the mechanism involved the increase of eNOS/NO, which linked to the decrease of blood pressure and the increase of apoptosis. This study provides practical guidance for salt intake in cases of RAS inhibitor usage clinically.

Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. β-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients.

Objective: This study aimed at evaluating the effects of candesartan and ramipril on liver fibrosis in patients with chronic hepatitis C. Methods: This randomized controlled prospective study involved 64 patients with chronic hepatitis C and liver fibrosis. Participants were randomized into 3 groups: group I (control group; n = 21), members of which received traditional therapy only; group 2 (ramipril group; n = 21), members of which received traditional therapy plus 1.25 mg/d oral ramipril; and group 3 (candesartan group; n = 22), members of which received traditional therapy plus 8 mg/d oral candesartan. Patients were assessed at baseline and 6 months after intervention through measuring of liver stiffness (Fibro-Scan; Echosens, Paris, France); evaluation of the serum levels of hyaluronic acid and transforming growth factor beta-1; and calculation of indices of liver fibrosis, including fibrosis index based on the 4 factors and aspartate transaminase-to-platelet-ratio index. Data were analyzed using paired t test and 1-way ANOVA followed by Tukey's honest significant difference test for multiple pairwise comparisons. Results: At baseline, the 3 study groups were statistically similar in demographic and laboratory data. After treatment, the 3 study groups showed significant decrease in liver stiffness, serum levels of hyaluronic acid and transforming growth factor beta-1, and indices of liver fibrosis compared with baseline data (P < 0.001). Six months after treatment, patients taking ramipril and candesartan showed significant improvement in all measured parameters compared with the control group. Additionally, the candesartan-treated group showed significant decrease in liver stiffness, biomarkers, and indices of liver fibrosis compared with ramipril recipients. Conclusions: The administration of ramipril and candesartan in patients with chronic hepatitis C with hepatic fibrosis was well tolerated and effective in improving liver fibrosis. angiotensin II receptor 1 (AT1) antagonist candesartan maintained antifibrotic effects more effectively than ramipril and may represent a safe and effective therapeutic strategy for liver fibrosis in patients with chronic liver diseases. ClinicalTrials.gov identifier: NCT03770936. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX) © 2022 Elsevier HS Journals, Inc.