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A new high-throughput optical sensor for captopril (CAP) is proposed. The sensor is based on the inhibitory effect of the analyte on the specific reaction of desferal with Fe(III) in an acidic medium. The whole analytical scheme was developed in micro-plates format combined with instrumental-free detection through an overhead book scanner. Dissolution testing was selected as an interesting application due to the generation of large amounts of samples during drug development. The method allowed the quantification of CAP up to 500 μM, with a lower limit of quantification LLOQ of 25 μM. 96 samples/standards could be processed simultaneously, obtaining a complete dissolution profile within 1 h (n = 12). Following validation, the obtained results were in accordance with the HPLC method recommended by the US Pharmacopeia. Finally, the greenness of the procedure was assessed by well-established tools such as the Green Analytical Procedure and Blue Applicability Grade indexes (77.5% score). [ABSTRACT FROM AUTHOR]

Aim: Studies have shown that renal hypertrophy seen in experimental hyperthyroidism induced by thyroxine (T4) is due to angiotensin (Ang) II. However, other renal effects of Ang II in experimental hyperthyroidism have not been investigated. In addition, Ang 1–7 is believed to be protective against renal injury, but its possible role in thyroxine-induced renal injury is not known. The aim of this study is to elaborate the role of Ang II in thyroxine-induced renal injury and the possible protective role of Ang 1–7. We hypothesize that Ang 1–7 will be as protective against thyroxine-induced renal injury as the use of an ACE inhibitor or an Ang II receptor blocker. Methods: Adult Sprague Dawley rats were used in this study and were divided into 5 groups: (1) Control (treated with vehicle), (2) Treated with thyroxine (T4, 100 µg/kg), (3) Treated with T4 and Ang 1–7 (500 µg/kg), (4) Treated with T4 and captopril (20 mg/kg), and (5) Treated with T4 and losartan (10 mg/kg). Parameters tested after fourteen days of treatment were creatinine clearance, protein excretion rate, glomerular volume, renal ACE1 and ACE2 protein expression. Data were compared using One-way-ANOVA followed by Tukey's HSD post hoc test. Results: Thyroxine caused glomerular hypertrophy and proteinuria but had no effect on glomerular filtration rate (GFR). Glomerular hypertrophy was prevented by losartan and captopril, but not by Ang 1–7. Captopril and losartan had no effect on GFR; however, Ang 1–7 caused an increase in GFR in T4-treated rats. The increase in protein excretion rate was prevented by losartan but not by captopril or Ang 1–7. Renal expression of ACE1 protein was not altered in any of the treatment groups except in captopril treated rats were ACE1 expression was increased. Renal ACE2 protein expression was only increased in T4-losartan-treated rats and not affected by any of the other treatments. Conclusion: We conclude that losartan was more protective than captopril against thyroxine-induced renal changes while Ang 1–7 offered no protection. [ABSTRACT FROM AUTHOR]

Uniform PtCoRuRhFe high-entropy alloy nanoflowers (HEANFs) were fabricated by a simple wet-chemical co-reduction method in oleylamine for quantitative colorimetric determination of captopril (CAP) based on multi-site synergistic signal amplification. Specifically, the peroxidase mimetic activity of the PtCoRuRhFe HEANFs was examined through catalysis of 3,3′,5,5′-tetramethylbenzidine (TMB) oxidation, whose catalytic mechanism was investigated by electron paramagnetic resonance (EPR) spectroscopy. The role of the ·O2− was figured out during the catalytic procedure. Further, the oxidation of TMB (oxTMB) can be effectively reduced by CAP, accompanied by quickly transforming the solution color from blue to colorless. More importantly, the absorbance at 652 nm is linearly related to the CAP concentration in a range 5.0–50.0 mM with a low detection limit of 2.82 mM. The method has been applied to the determination of CAP in human urine samples. It offers a simple and high-efficiency method for facile and visual detection of CAP in hospitals. [ABSTRACT FROM AUTHOR]

Hypertension drives the development of concentric left ventricular hypertrophy (LVH). However, the relative contribution of pentraxin‐3 (PTX‐3), a novel marker for inflammatory cardiovascular disease, in the hypertrophic response to pressure overload has not been adequately elucidated. We investigated the role of PTX‐3 in the development of LVH in spontaneously hypertensive rats (SHR), untreated and treated with either captopril (an ACE inhibitor) or hydralazine (a non‐specific vasodilator). Three‐month‐old SHR received either 20 mg/kg/day hydralazine (SHR + H, n = 6), 40 mg/kg/day captopril (SHR + C, n = 6), or plain gelatine cubes (untreated SHR, n = 7) orally for 4 months. Wistar Kyoto rats (WKY, n = 7) were used as the normotensive controls. Blood pressure (BP) was measured using the tail‐cuff method. Cardiac geometry and function were determined using M‐mode echocardiography. Circulating concentrations of inflammatory markers were measured in plasma by ELISA. LV fibrosis and cardiomyocyte width were assessed by histology. Relative mRNA expression of PTX‐3 was determined in the LV by RT‐PCR. Untreated SHR exhibited greater systolic BP and relative wall thickness (RWT) compared to WKY. Captopril and hydralazine normalized BP but only captopril reversed RWT in SHR. Circulating PTX‐3 and VCAM‐1 levels were elevated in untreated SHR and reduced with captopril and hydralazine. Circulating PTX‐3 was positively associated with systolic BP but lacked independent relations with indices of LVH. LV relative mRNA expression of PTX‐3 was similar between the groups. PTX‐3 may not be involved in the development of LVH in SHR, but plausibly reflects the localized inflammatory milieu associated with hypertension. [ABSTRACT FROM AUTHOR]

We developed a sustained-release transdermal drug delivery system (TDDS) containing simvastatin (SIM) and captopril (CAP) to treat hypertension and hyperlipidemia and overcome treatment drawbacks, including significant liver first-pass effects, low bioavailability, and the short half-life of SIM and CAP oral tablets. We used a transdermal diffusion meter to preselect the formula of the SIM-CAP TDDS. Based on in vitro permeation experiments, we optimized the formula of the SIM-CAP TDDS to include 24% SIM, 24% CAP, 34% polyvinyl alcohol (PVA), 16% oleic acid (OA)–azone, and 2% polyacrylic acid resin II. We evaluated the optimized SIM-CAP TDDS formula by its appearance, stability, stickiness, drug content, in vivo pharmacokinetics, and skin irritation tests. The results indicated that the patch had good stability and stickiness. The SIM and CAP contents were 5.02 ± 0.41 mg/cm2 in the 1 cm2 SIM-CAP TDDS. The pharmacokinetic results indicated that the system continuously released SIM and CAP for 24 h and significantly enhanced their bioavailability, with a higher area under the curve. The SIM-CAP TDDS exhibits a sustained-release effect with good characteristics and pharmacokinetics. And it is safe and has no irritating effects on the skin; therefore, it is an ideal formulation. [ABSTRACT FROM AUTHOR]

Objectives: Captopril is a commonly used therapeutic agent in the management of renovascular hypertension (high blood pressure), congestive heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy. Captopril has been found to interact with proteins that are significantly associated with bladder cancer (BLCA), suggesting that it could be a potential medication for BLCA patients with concurrent hypertension. Methods: DrugBank 5.0 was utilized to identify the direct protein targets (DPTs) of captopril. STRING was used to analyze the multiple protein interactions. TNMPlot was used for comparing gene expression in normal, tumor, and metastatic tissue. Then, docking with target proteins was done using Autodock. Molecular dynamics simulations were applied for estimate the diffusion coefficients and mean-square displacements in materials. Results: Among all these proteins, MMP9 is observed to be an overexpressed gene in BLCA and its increased expression is linked to reduced survival in patients. Our findings indicate that captopril effectively inhibits both the wild type and common mutated forms of MMP9 in BLCA. Furthermore, the LCN2 gene, which is also overexpressed in BLCA, interacts with captopril-associated proteins. The overexpression of LCN2 is similarly associated with reduced survival in BLCA. Through molecular docking analysis, we have identified specific amino acid residues (Tyr179, Pro421, Tyr423, and Lys603) at the active pocket of MMP9, as well as Tyr78, Tyr106, Phe145, Lys147, and Lys156 at the active pocket of LCN2, with which captopril interacts. Thus, our data provide compelling evidence for the inhibitory potential of captopril against human proteins MMP9 and LCN2, both of which play crucial roles in BLCA. Conclusion: These discoveries present promising prospects for conducting subsequent validation studies both in vitro and in vivo, with the aim of assessing the suitability of captopril for treating BLCA patients, irrespective of their hypertension status, who exhibit elevated levels of MMP9 and LCN2 expression. [ABSTRACT FROM AUTHOR]

Background and Purpose: This study analyses whether first‐line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension. Experimental Approach: Twenty‐week‐old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR‐treated groups to SHR recipients for 3 weeks. Key results: Faeces from SHR showed gut dysbiosis, characterized by lower acetate‐ and higher lactate‐producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate‐producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate‐producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR‐amlodipine to SHR decreased BP, ameliorated aortic endothelium‐dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR‐hydrochlorothiazide did not have these effects. Conclusions and Implications: First‐line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo‐protective effect induced by amlodipine involves gut microbiota reshaping and gut‐immune system communication. [ABSTRACT FROM AUTHOR]

Angiogenesis is essential for many tumours to grow and metastasise, including breast tumours. Captopril, an Angiotensin- Converting Enzyme inhibitor is known to have anti-angiogenic activity. Recently, novel derivatives of captopril that include thiosemicarbazide moiety have shown enhanced ACE inhibition activity compared to captopril. This study aimed to assess the anti-angiogenic activity of one of these derivatives designated as (8) in the Estrogen receptor-positive MCF-7, and the Estrogen-Progesterone receptor-negative AMJ13 breast cancer cells. The study included a microarray screening for 24 angiogenic factors, and genes were confirmed by RT-qPCR. Results demonstrated a stronger anti-angiogenic effect in the MCF-7 cells compared to those on AMJ13. In MCF7, the derivative caused a significant decrease in the pro-angiogenic bFGF mRNA, VEGF-A mRNA expression, thrombopoietin protein level, PECAM -1 (CD31) mRNA, G-CSF protein, and a significant increase in the anti-angiogenic factors MIG mRNA level, IL-13 protein level, PF-4 both protein and mRNA level. The derivative also significantly decreased TIMP-1 mRNA and IFN-γ protein levels, whereas in AMJ13, a significant increase in MIG protein expression (but not mRNA), a significant decrease in IL-β protein expression, as well as thrombopoietin and PECAM-1 mRNA were documented. This work has shown the thiosemicarbazide derivative of captopril (8) as a potential anti-angiogenic agent targeting multiple factors in the angiogenesis of breast cancer cells. This study has demonstrated derivative (8) as a very promising molecule to be further investigated in other modes of angiogenesis and types of cancer. [ABSTRACT FROM AUTHOR]

Context Olive leaf extract (OLE) is rich in phenolic compounds, which are known for their health benefits. Cardiovascular diseases, primarily coronary heart disease and stroke, are leading causes of mortality globally. Objective This systematic review aimed to assess the impact of OLE on cardiometabolic risk factors in adults. The selection of studies was based on intervention and outcomes, using relevant search descriptors. Data Sources The databases PubMed, EMBASE, and Web of Science were systematically searched for pertinent studies published up to August 2021. Data Extraction Only randomized clinical trials, either cross-over or parallel, involving adult individuals aged ≥18 years, were considered. Additionally, trials that had a comparative or placebo group and used pure OLEs for oral treatment were included. Data Analysis Twelve randomized clinical trials (RCTs) met the inclusion criteria. These trials had follow-up periods ranging from 2 days to 12 weeks and involved 703 patients aged 18 years–79 years. The outcomes demonstrated a positive correlation between the intervention group and glucose metabolism (4 RCTs), blood pressure (2 RCTs), lipid profile (2 RCTs), and inflammatory markers (2 RCTs). The RoB2 tool and the GRADE system were used to evaluate the risk of bias and the quality of evidence in the studies. Conclusions In the meta-analysis, fasting glycemia, as evaluated in studies using a low dose of OLE, showed a significant result favoring the control group. To obtain more consistent results, further clinical studies in humans, using similar methodologies, are required. Systematic Review Registration PROSPERO registration no. CRD42020200877. [ABSTRACT FROM AUTHOR]

Abstract A major and irreversible complication of diabetes is diabetic peripheral neuropathy (DPN), which can lead to significant disability and decreased quality of life. Prior work demonstrates the peptide hormone Angiotensin II (Ang II) is released locally in neuropathy and drives inflammation and impaired endoneurial blood flow. Therefore, we proposed that by utilizing a local thermoresponsive hydrogel injection, we could deliver inhibitors of angiotensin-converting enzyme (ACE) to suppress Ang II production and reduce nerve dysfunction in DPN through local drug release. The ACE inhibitor captopril was encapsulated into a micelle, which was then embedded into a reversibly thermoresponsive pluronics-based hydrogel matrix. Drug-free and captopril-loaded hydrogels demonstrated excellent product stability and sterility. Rheology testing confirmed sol properties with low viscosity at ambient temperature and increased viscosity and gelation at 37 °C. Captopril-loaded hydrogels significantly inhibited Ang II production in comparison to drug-free hydrogels. DPN mice treated with captopril-loaded hydrogels displayed normalized mechanical sensitivity and reduced inflammation, without side-effects associated with systemic exposure. Our data demonstrate the feasibility of repurposing ACE inhibitors as locally delivered anti-inflammatories for the treatment of sensory deficits in DPN. To the best of our knowledge, this is the first example of a locally delivered ACE inhibitor for the treatment of DPN.

Background Primary hyperaldosteronism (PA) has been recommended by numerous hypertension guidelines to expand screening, early diagnosis and treatment, as a secondary hypertension disease with the highest incidence, great cardiovascular and cerebrovascular dangers but high cure rate after surgery. However, the diagnosis, classification and clinical outcomes evaluation of these patients are varied and controversial. Captopril challenge test (CCT) is expected to provide whole-course management for PA patients because it is convenient, safe and can be used directly in the community or outpatient clinic. Objective To explore the diagnostic efficacy, classification and biochemical remission assessment of CCT in patients with PA. Methods The study population consisted of 824 patients who completed the cause screening for hypertension and were enrolled in the Department of Endocrinology and Metabolism, West China Hospital, Sichuan University from October 1 th 2020 to December 30 th 2022. After screening, 247 patients with PA and 123 patients with essential hypertension (EH) were enrolled, and PA was classified into aldosterone-producing adenoma (APA, 81 patients), idiopathic hyperaldosteronism (IHA, 55 patients), and uncategorized PA (u-PA, 111 patients). The differences among the four groups were compared and the receiver operating characteristic (ROC) curve analysis showed the diagnostic performance for the prediction of PA. Secondly, the ROC curves of each post-CCT index for APA and IHA respectively were plotted. Finally, according to the postoperative clinical outcomes, the patients with unilateral adrenal resection were divided into three groups: clinical remission, clinical improvement, and no remission group. The difference between the three groups was compared, and the cut-off point of biochemical remission of CCT in APA patients was analyzed. Results The post-CCT plasma aldosterone concentration (PAC) level had the highest diagnostic efficiency for PA (AUC=0.921, 95%CI=0.893-0.950), and the cut-off was 11.7 ng/dL. The sensitivity and specificity respectively was 84.6% and 86.0%. The post-CCT aldosterone to renin ratio (ARR) also had a good diagnostic efficacy for PA (AUC=0.868, 95%CI=0.823-0.923). The cut-off was 2.8 (ng/dL) / (mU/L), and the sensitivity and specificity respectively were 82.2% and 81.0%. The post-CCT PAC>17 ng/dL can assist in the diagnosis of APA subtypes. When post-CCT PAC

Bacteria are becoming increasingly resistant to antibiotics, therefore there is an urgent need for new classes of antibiotics to fight antibiotic resistance. Mammals do not express Na -acetyl-L-ornithine deacetylase (ArgE), an enzyme that is critical for bacterial survival and growth, thus ArgE represents a promising new antibiotic drug target, as inhibitors would not suffer from mechanism-based toxicity. A new ninhydrin-based assay was designed and validated that included the synthesis of the substrate analog N5, N5-di-methyl Na-acetyl-L-ornithine (kcat/Km = 7.32 ± 0.94 χ 104M-1s-1). This new assay enabled the screening of potential inhibitors that absorb in the UV region, and thus is superior to the established 214 nm assay. Using this new ninhydrin-based assay, captopril was confirmed as an ArgE inhibitor (IC50 = 58.7 μM; Ki = 37.1 ± 0.85 μM), and a number of phenylboronic acid derivatives were identified as inhibitors, including 4(diethylamino)phenylboronic acid (IC50 = 50.1 μM). Selected inhibitors were also tested in a thermal shift assay with ArgE using SYPRO Orange dye against Escherichia coli ArgE to observe the stability of the enzyme in the presence of inhibitors (captopril Ki = 35.9 ± 5.1 μM). The active site structure of di-Zn EcArgE was confirmed using X-ray absorption spectroscopy, and we reported two X-ray crystal structures of E. coli ArgE. In summary, we describe the development of a new ninhydrin-based assay for ArgE, the identification of captopril and phenylboronic acids as ArgE inhibitors, thermal shift studies with ArgE + captopril, and the first two published crystal structures of ArgE (mono-Zn and di-Zn). [ABSTRACT FROM AUTHOR]

This study assessed the pharmacokinetics (PKs) and pharmacodynamics (PDs) of two antihypertensive drugs, nifedipine and captopril, by exploring their main (blood pressure [BP]) and secondary effects (heart rate [HR] and QT interval [QT]) in spontaneously hypertensive rats. This study aimed to assess the relationship between PKs and PDs. Using these PD parameters, BP, HR, and QT during coadministration were estimated. The coadministration of nifedipine and captopril resulted in an increase in nifedipine's total body clearance (CLtot) and a reduction in its mean residence time (MRT) with an increase in the terminal elimination half‐life (t1/2) and volume of distribution at steady state (Vdss) of captopril. However, no significant PK interactions were observed. During monotherapy, BP reduced rapidly following nifedipine infusion. Subsequently, despite the increase in nifedipine plasma concentration, BP recovered, likely because of homeostasis. Similar results were observed with coadministration. Subsequently, BP demonstrated a sustained reduction that was greater than or equal to the additive effect estimated from each PK. Captopril exhibited a minimal effect on HR, except for a transient increase observed immediately after starting infusion, consistent with observations during coadministration. Subsequently, the HR reduction was nearly equal to that calculated from the nifedipine PK. QT prolongation was more rapid with captopril than with nifedipine. Although QT prolongation during the initial 60 min of coadministration was approximately the sum of both effects, the recovery period to baseline QT was faster than that in the simulation. [ABSTRACT FROM AUTHOR]

The combination of silica nanoparticles with fluorescent molecularly imprinted polymers (Si-FMIPs) prepared by a one-pot sol-gel synthesis method to act as chemical sensors for the selective and sensitive determination of captopril is described. Several analytical parameters were optimized, including reagent ratio, solvent, concentration of Si-FMIP solutions, and contact time. Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and the ninhydrin assay were used for characterization. The selectivity was evaluated against molecules belonging to other drug classes, such as fluoroquinolones, nonacid nonopioids, benzothiadiazine, alpha amino acids, and nitroimidazoles. Under optimized conditions, the Si-FMIP-based sensor exhibited a working range of 1–15 µM, with a limit of detection (LOD) of 0.7 µM, repeatability of 6.4% (n = 10), and suitable recovery values at three concentration levels (98.5% (1.5 µM), 99.9% (3.5 µM), and 99.2% (7.5 µM)) for wastewater samples. The sensor provided a working range of 0.5–15 µM for synthetic urine samples, with an LOD of 0.4 µM and a repeatability of 7.4% (n = 10) and recovery values of 93.7%, 92.9%, and 98.0% for 1.0 µM, 3.5 µM, and 10 µM, respectively. In conclusion, our single-vessel synthesis approach for Si-FMIPs proved to be highly effective for the selective determination of captopril in wastewater and synthetic urine samples. [ABSTRACT FROM AUTHOR]

This study investigated the effect of captopril (Cap) on spinal cord ischemia-reperfusion injury (SCII) in rats. Twenty-four adults male Wistar rats were randomly divided into four groups of six animals each: spinal cord ischemia-reperfusion (SCI-R) with Cap (SCI-R + Cap), SCI-R, shamoperated with Cap (SHAM + Cap), and SHAM. The 24 hr and 90 min before ischemia induction, Cap was administered intragastrically (100 mg kg-1) to the SHAM + Cap and SCI-R + Cap groups. Abdominal aortic clamping was performed in the SCI-R and SCI-R + Cap groups for 40 min. Hindlimb motor function was evaluated using the Tarlov Scale at 4, 6, 12, 24, 48, and 60 hr after SCII. The malondialdehyde (MDA), the ferric-reducing ability of plasma (FRAP) and prooxidantantioxidant balance (PAB) values were also measured. Throughout the study period, the SCI-R group had significantly lower motor function scores compared to the other groups. The MDA and PAB levels were higher and the FRAP value was lower in the SCI-R group compared to in the SHAM group. The SCI-R + Cap had higher motor function scores compared to the SCI-R group at all time points. There were no significant differences in MDA concentration, FRAP and PAB values between the SCI-R + Cap and SCI-R groups. Captopril may act as a protective agent against SCII in rats based on hind limb motor function assessment. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r2 value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device. [ABSTRACT FROM AUTHOR]

Purpose: Alginate beads intended to float in the stomach have several advantages over the traditional oral dosage forms. However, the formulation of these beads to deliver hydrophilic drugs such as captopril is a big challenge in terms of entrapment efficiency (EE) and extending the drug release. Here, we investigated the feasibility of using the double emulsion (DE) technique during the preparation of alginate floating beads to enhance the EE. This technique allows the incorporation of captopril into the oil droplets, the floating agent within the beads, which provides a hydrophobic barrier preventing drug loss. Methods: Different DE beads were prepared using ionotropic gelation methods and compared with ordinary oil-entrapped beads based on the floating properties, EE, and drug release. Results: The results revealed that all the prepared beads have comparable floating properties, however, the EE was significantly increased from 11% for ordinary beads to 25% for DE beads. Moreover, the release of captopril from DE beads was markedly prolonged in comparison to that from ordinary beads. The SEM images clearly showed that the use of surfactant, tween 80, has a significant effect on the prepared beads through stabilizing the primary emulsion, maintain the drug dispersed within the oil droplets, and producing smooth beads with well-crosslinked surface and small well-dispersed oil droplets. Conclusion: The findings of this study highlighted the potential of DE alginate beads as a promising drug delivery system, addressing the challenges associated with hydrophilic drug encapsulation. [ABSTRACT FROM AUTHOR]

Abstract Background Streptozotocin (STZ) is a glucose analogue commonly used for inducing diabetes in experimental animals. This study is intended to investigate the ability of captopril (Cap) pretreatment to augment STZ-induced diabetogenic effect in an experimental rat model. If this hypothesis were proven, Cap administration to rats could reduce the dosage of STZ by augmenting its effect and resulting in a subsequent reduction in STZ cost. Forty-two adult male Wistar rats were randomly divided into seven groups: a control group that fed a normal diet, whereas the other six experimental groups were fed a high-fat diet (HFD). The six groups were then divided into STZ-30, STZ-30-Cap, STZ-40, STZ-40-Cap, STZ-50, and STZ-50-Cap. All Cap-received groups were supplemented with 50 mg/kg Cap orally one hour just before intraperitoneal (I.P.) injection of STZ. 30-STZ, 40-STZ, and 50-STZ-treated groups were injected once with STZ I.P. at doses of 30, 40, and 50 mg/kg, respectively. An intraperitoneal glucose tolerance test (IPGTT) was done. Pancreatic tissue was obtained to measure Tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), and nitric oxide (NO) by enzyme-linked immunosorbent assay (ELISA) and glucose transporter 2 (GLUT2) gene expression by reverse transcription polymerase chain reaction (RT-PCR). Pancreatic sections were examined by hematoxylin and eosin (H&E) stain, and immunohistochemical staining by anti-insulin and anti-TNF-α antibodies. Results Results indicated that administration of Cap before STZ in different doses significantly augmented the hyperglycemic state that was evident by intraperitoneal glucose tolerance test, and markedly increased pancreatic pro-inflammatory markers. Histological analysis of islets of Langerhans indicated degeneration with extensive vacuolations associated with a significant decrease in mean area % of insulin immunoreactivity and an increase in optical density of TNF-α immunoreactivity. Conclusion These findings pointed to the ability of captopril pretreatment to augment the hyperglycemic state and the diabetogenic response that was induced secondary to STZ injection in an experimental rat model.

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Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril's effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42–0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI. [ABSTRACT FROM AUTHOR]

In this research, we demonstrated a chondroitin sulfate (CHS), polyvinylpyrrolidone (PVP), and 2-acrylamide-2-methylpropane sulphonic acid (AMPS)-based captopril-loaded mucoadhesive hydrogel that efficiently facilitated the sustained release of drug molecules and is developed by radical polymerization technique. The designed hydrogel network is initially analyzed for the influence of different formulation ingredients as well as their quantities on swelling behavior and mucoadhesion capacity. The physical interaction along with biocompatibility of CHS/PVP-co-poly (AMPS) hydrogels is illustrated by utilizing FT-IR and histopathological analysis. Thermal stability, conversion of crystalline nature ingredient to amorphous nature hydrogel matrix, prolonged and sustained in vitro released behavior at 1.2 pH, porous surface morphology, and enhanced mucoadhesive characteristics are ensured by thermal analysis, XRD, drug in vitro released profile, SEM, and ex-vivo mucoadhesive analysis. Interestingly, the findings suggest that CHS/PVP-co-poly (AMPS)-based hydrogel systems are viable candidates for sustained delivery of captopril by enhancing its adherence with the gastric mucus layer and decreasing its dose frequency. [ABSTRACT FROM AUTHOR]

Background: To explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing. Methods: A total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value. Results: The average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (p<0.05). The optimal cutoff value was 10.7 ng/dL for post-CCT PAC, 6.8 ng/dL for post-SIT PAC, and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cutoff value for patients who were <50 years old was 11.5 ng/dL for post-CCT PAC and 8.4 ng/dL for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of age 50 or older. Conclusion: Compared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age. [ABSTRACT FROM AUTHOR]

Background: Streptozotocin (STZ) is a glucose analogue commonly used for inducing diabetes in experimental animals. This study is intended to investigate the ability of captopril (Cap) pretreatment to augment STZ-induced diabetogenic effect in an experimental rat model. If this hypothesis were proven, Cap administration to rats could reduce the dosage of STZ by augmenting its effect and resulting in a subsequent reduction in STZ cost. Forty-two adult male Wistar rats were randomly divided into seven groups: a control group that fed a normal diet, whereas the other six experimental groups were fed a high-fat diet (HFD). The six groups were then divided into STZ-30, STZ-30-Cap, STZ-40, STZ-40-Cap, STZ-50, and STZ-50-Cap. All Cap-received groups were supplemented with 50 mg/kg Cap orally one hour just before intraperitoneal (I.P.) injection of STZ. 30-STZ, 40-STZ, and 50-STZ-treated groups were injected once with STZ I.P. at doses of 30, 40, and 50 mg/kg, respectively. An intraperitoneal glucose tolerance test (IPGTT) was done. Pancreatic tissue was obtained to measure Tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), and nitric oxide (NO) by enzyme-linked immunosorbent assay (ELISA) and glucose transporter 2 (GLUT2) gene expression by reverse transcription polymerase chain reaction (RT-PCR). Pancreatic sections were examined by hematoxylin and eosin (H&E) stain, and immunohistochemical staining by anti-insulin and anti-TNF-α antibodies. Results: Results indicated that administration of Cap before STZ in different doses significantly augmented the hyperglycemic state that was evident by intraperitoneal glucose tolerance test, and markedly increased pancreatic pro-inflammatory markers. Histological analysis of islets of Langerhans indicated degeneration with extensive vacuolations associated with a significant decrease in mean area % of insulin immunoreactivity and an increase in optical density of TNF-α immunoreactivity. Conclusion: These findings pointed to the ability of captopril pretreatment to augment the hyperglycemic state and the diabetogenic response that was induced secondary to STZ injection in an experimental rat model. [ABSTRACT FROM AUTHOR]

The recurrence of colorectal liver metastasis (CRLM) following liver resection is common; approximately 40% of patients will experience tumor recurrence post-surgery. Renin–angiotensin inhibitors (RASis) have been shown to attenuate the growth and progression of CRLM in pre-clinical models following liver resection. This study examined the efficacy of the RASi captopril on patient-derived colorectal liver metastasis organoids. Patient-derived organoids (PDOs) were established using fresh samples of colorectal liver metastasis from appropriately consented patients undergoing liver resection. To mimic the regenerating liver post-CRLM liver resection, PDOs were cultured under hepatocyte regeneration conditions in vitro. CRLM PDOs were established from three patients' parent tissue. CRLM PDOs and parent tissue expressed markers of colorectal cancer, CDX2 and CK20, consistently. Furthermore, CRLM PDOs treated with captopril showed a dose dependent reduction in their expansion in vitro. In conclusion, CRLM PDOs recapitulate in vivo disease and displayed a dose-dependent response to treatment with captopril. RASis may be an additional viable treatment for patients with CRLM. [ABSTRACT FROM AUTHOR]

Abstract This study assessed the pharmacokinetics (PKs) and pharmacodynamics (PDs) of two antihypertensive drugs, nifedipine and captopril, by exploring their main (blood pressure [BP]) and secondary effects (heart rate [HR] and QT interval [QT]) in spontaneously hypertensive rats. This study aimed to assess the relationship between PKs and PDs. Using these PD parameters, BP, HR, and QT during coadministration were estimated. The coadministration of nifedipine and captopril resulted in an increase in nifedipine's total body clearance (CLtot) and a reduction in its mean residence time (MRT) with an increase in the terminal elimination half‐life (t1/2) and volume of distribution at steady state (Vdss) of captopril. However, no significant PK interactions were observed. During monotherapy, BP reduced rapidly following nifedipine infusion. Subsequently, despite the increase in nifedipine plasma concentration, BP recovered, likely because of homeostasis. Similar results were observed with coadministration. Subsequently, BP demonstrated a sustained reduction that was greater than or equal to the additive effect estimated from each PK. Captopril exhibited a minimal effect on HR, except for a transient increase observed immediately after starting infusion, consistent with observations during coadministration. Subsequently, the HR reduction was nearly equal to that calculated from the nifedipine PK. QT prolongation was more rapid with captopril than with nifedipine. Although QT prolongation during the initial 60 min of coadministration was approximately the sum of both effects, the recovery period to baseline QT was faster than that in the simulation.

IntroductionDespite the high phenolic content of Annona muricata, little is known about its anti-hypertensive and antihyperlipidemic properties. This study evaluated the anti-hypertensive and antihyperlipidemic potential of A. muricata leaf extracts.Materials and methodsForty-two male Wistar rats were divided into seven groups of six animals each. N-nitro-L-arginine methyl ester (L-NAME) was used to induce hypertension and hyperlipidemia.ResultsPhytochemical screening of Annona muricata leaf extracts (AMLE) revealed the presence of saponins, alkaloids, flavonoids, tannins, coumarins, steroids, terpenoids, and phenols. Comparing the methanol extract with the ethyl acetate fraction, quantification revealed that the methanol extract contained more phenolics, flavonoids, and alkaloids. The AMLE rats significantly reduced triglycerides, total cholesterol, LDL, VLDL, atherogenic index, coronary risk index, and blood pressure. The significant decrease in GSH, catalase, SOD, GST, and oxidative stress markers (MDA, nitrites, and MPO) was reversed by AMLE in a dose-dependent manner. Also, the elevated serum levels of TNF-α and IL-1β in the hypertensive rats were attenuated in the treatment groups.DiscussionThis study suggests the potential ameliorative effects of Annona muricata leaf extracts against L-NAME-induced hypertension in rats. Notably, the study showed the antioxidant and anti-inflammatory properties of A. muricata leaf extracts, which is seen in its ability to attenuate oxidative stress and inflammatory cytokines in L-NAME-induced hypertensive rats. A. muricata extracts also decreased atherogenic risk and improved lipid profiles.

Abstract Purpose Patients are typically diagnosed with both hypertension and fibrosarcoma. Medical oncologists must prescribe suitable anti-hypertensive medications while considering anti-tumor drugs. Recently, immunotherapy has become prominent in cancer treatment. Nonetheless, it is unknown what role anti-hypertensive medications will play in immunotherapy. Methods We examined the effects of six first-line anti-hypertensive medications on programmed cell death protein 1 antibody (PD1ab) in tumor treatment using a mouse model of subcutaneous fibrosarcoma. The drugs examined were verapamil, losartan, furosemide, spironolactone, captopril, and hydrochlorothiazide (HCTZ). The infiltration of CD8+ T cells was examined by immunohistochemistry. Additionally, several in vitro and in vivo assays were used to study the effects of HCTZ on human fibrosarcoma cancer cells to explore its mechanism. Results Verapamil suppressed tumor growth and showed an improved effect on the tumor inhibition of PD1ab. Captopril did not affect tumor growth but brought an unexpected benefit to PD1ab treatment. In contrast, spironolactone and furosemide showed no effect on tumor growth but had an offset effect on the PD1ab therapy. Consequently, the survival time of mice was also significantly reduced. Notably, losartan and HCTZ, especially HCTZ, promoted tumor growth and weakened the effect of PD1ab treatment. Consistent results were observed in vivo and in vitro using the human fibrosarcoma cell line HT1080. We determined that the Solute Carrier Family 12 Member 3 (SLC12A3), a known target of HCTZ, may be the principal factor underlying its effect-enhancing properties through mechanism studies employing The Cancer Genome Atlas (TCGA) data and in vivo and in vitro assays. Conclusion Verapamil and captopril potentiated the anti-tumor effect of PD1ab, whereas spironolactone and furosemide weakened the effect of PD1ab on tumor inhibition. Alarmingly, losartan and HCTZ promoted tumor growth and impaired the effect of PD1ab. Furthermore, we preliminarily found that HCTZ may promote tumor progression through SLC12A3. Based on this study, futher mechanism researches and clinical trials should be conducted in the future.

Abstract Preserving the environment, reducing the amount of waste resulting from chemical trials, and reducing the amount of energy consumed have currently become a pivotal global trend. An analytical quality by design (AQbD) based eco-friendly TLC-densitometric method was implemented for quantifying two antihypertensive agents, captopril (CPL) and hydrochlorothiazide (HCZ), along with their impurities; captopril disulphide (CDS), chlorothiazide (CTZ) and salamide (SMD). The analytical target profile (ATP) was first identified, followed by selecting the critical analytical attributes (CAAs), such as retardation factors and resolution between the separated peaks. Critical method parameters (CMPs) that may have a crucial influence on CAAs were identified and emanated through the quality risk assessment phase. A literature survey-based preliminary studies were performed, followed by optimization of the selected CMPs through a custom experimental design to attain the highest resolution with optimum retardation factors. Moreover, method robustness was also tested by testing the design space. Complete separation of the drugs and their impurities was achieved using ethyl acetate: glacial acetic acid (6: 0.6, v/v) as a developing system applied to a 12 cm length TLC plate at room temperature with UV scanning at 215 nm. Calibration graphs were found to be linear in the ranges of (0.70–6.00), (0.10–2.00), (0.20–1.00), (0.07–1.50) and (0.05–1.00) µg/band corresponding to CPL, HCZ, CDS, CTZ, and SMD, respectively. Four different green metric tools were used to evaluate the greenness profile of the proposed method, and results showed that it is greener than the reported HPLC method. Method whiteness assessment was also conducted. Moreover, the method performance was evaluated following the ICH guidelines, and the outcomes fell within the acceptable limits. The developed method could be approved for routine assay of the cited components in their pharmaceutical formulations and bulk powder without interference from the reported impurities. The issue of concern is saving money, especially in developing countries.

We developed a sustained-release transdermal drug delivery system (TDDS) containing simvastatin (SIM) and captopril (CAP) to treat hypertension and hyperlipidemia and overcome treatment drawbacks, including significant liver first-pass effects, low bioavailability, and the short half-life of SIM and CAP oral tablets. We used a transdermal diffusion meter to preselect the formula of the SIM-CAP TDDS. Based on in vitro permeation experiments, we optimized the formula of the SIM-CAP TDDS to include 24% SIM, 24% CAP, 34% polyvinyl alcohol (PVA), 16% oleic acid (OA)–azone, and 2% polyacrylic acid resin II. We evaluated the optimized SIM-CAP TDDS formula by its appearance, stability, stickiness, drug content, in vivo pharmacokinetics, and skin irritation tests. The results indicated that the patch had good stability and stickiness. The SIM and CAP contents were 5.02 ± 0.41 mg/cm2 in the 1 cm2 SIM-CAP TDDS. The pharmacokinetic results indicated that the system continuously released SIM and CAP for 24 h and significantly enhanced their bioavailability, with a higher area under the curve. The SIM-CAP TDDS exhibits a sustained-release effect with good characteristics and pharmacokinetics. And it is safe and has no irritating effects on the skin; therefore, it is an ideal formulation.