The use of combined sewer systems is associated with frequent overflow events and discharges of untreated wastewater containing micropollutants, including active pharmaceutical ingredients (APIs). The aim of this study was to evaluate the impact of weather-related factors on the presence of pharmaceuticals and illicit substances and assess the related environmental risk. To address this goal, three sites in the surroundings of the city of Vitoria-Gasteiz were sampled in April (dry week) and November (wet week): Betoño Pond in the Salburua Wetlands, and Zadorra River before and after receiving the Crispijana wastewater treatment plant's (WWTP) effluent. An environmental risk assessment was performed by measuring the hazard quotients for each compound, in addition to individual chemical enantiomers of amphetamine and 3,4-methylenedioxymethamphetamine. A total of 33 out of 102 substances were detected in at least one of the samples and a minimum of 6 APIs in all sample sites. Post-WWTP samples taken in autumn (wet week) presented the highest cumulative concentration (7739 ng L-1). Risk quotients of 12 APIs in the most contaminated site in the rainy weather sampling period reached values >1: diclofenac (3.12) and eprosartan (1.59).

Because no information is available on the use of eprosartan during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Angiotensin receptor blockers (ARBs) have been relatively less explored in the field of neuroprotection and dementia; however, ample preclinical and clinical evidence suggests their potential cognitive benefits. Despite these findings, there remains limited evidence on precise mechanistic pathways involved, highlighting the critical need to bridge the gap. In our previous work, we presented the beneficial effect of azilsartan in a dementia model and observed promising neuroprotective outcomes. Building on these findings, this study sought to compare the activity of azilsartan with other commonly used ARBs, including telmisartan, olmesartan, valsartan, eprosartan, irbesartan, and candesartan, using an integrative network pharmacology approach. Our network analysis identified 12 key target proteins implicated in dementia pathology, which were further subjected to docking studies with the seven ARBs, revealing strong binding affinities of azilsartan, olmesartan, and telmisartan with critical signaling proteins, including AKT1, PIK3CA, and PIK3CB. Molecular dynamics simulations further confirmed the stability and favorable interactions of azilsartan with these targets. To experimentally validate these predictions, in vivo studies were conducted in a scopolamine-induced memory-impaired model, which demonstrated significant restoration of the levels of AKT1 and PIK3CA. These findings clearly demonstrate the PI3K/AKT modulating effects of azilsartan, reinforcing its repurposing potential in dementia and related disorders, thereby expanding novel therapeutic opportunities within this drug class.

Traumatic brain injury is not constrained only to the brain but delayed secondary events disturb the end organ functioning via intense response of three homeostatic mechanisms such as sympathetic activity, inflammation, and immunosuppression. Current study involved weight drop model to induce TBI in Swiss albino mice. Eprosartan was administered orally after 30-45 min post injury to mice in 0.35 mg/kg and 0.7 mg/kg doses. Mice were tested for neurobehavioral alterations and multiple organs, including brain, heart, lungs, liver, and kidney were excised for further edema, biochemical, inflammatory, catecholamine, gene expression and histopathological estimations at both acute and chronic phases of injury. Results highlighted that Epro improved neurobehavioral performance, maintained the BBB and lung integrity. It also ameliorated the oxidative stress as well as docking studies exhibited strong binding affinity of Epro for HMGB1 and PDL-1, that further supported by low tissue HMGB1 and serum IL-6 and TNF-α cytokines levels which halted the systemic hyperinflammation. Moreover, Epro treatment successfully restored the cardiac, hepatic and kidney function through stabilized serum biomarkers with declined plasma noradrenaline levels that subsides the sympathetic storm. Considerably, a bizarre cellular morphology was displayed by the organs in acute phase of injury whereas Epro reversed the morphological changes at chronic stage. Also, epro encouraged the PD-1/PDL-1 and IL-10 gene expression in the tissues that regulates immune response. Thus, it is concluded that Epro exerts its organ protective effect against MODS via AT1/SNS pathway inhibition.

Despite growing evidence for the renin-angiotensin system (RAS) involvement in Parkinson's disease (PD), its role in microglial polarization during disease progression remains unclear. This study explored the ability of modulating RAS using eprosartan, an AT1R antagonist, and xanthenone, an ACE2 activator, to support microglial M2 polarization in rats with PD highlighting the roles of miR-155, protein phosphatase 2 A (PP2A), and mitogen-activated protein kinase phosphatase 1 (MKP-1). Rotenone (1.5 mg/kg) was administered to Wistar rats to induce PD, with concurrent treatments of eprosartan (60 mg/kg/day) or xanthenone (2 mg/kg/day) for 28 days. Both agents improved motor function and neuronal damage, as evidenced by behavioral, histopathological, and immunohistochemical analyses. Eprosartan and xanthenone enhanced tyrosine hydroxylase activity and reduced α-synuclein accumulation in the substantia nigra. Eprosartan and xanthenone modulated the RAS axis by reducing angiotensin II level and increasing ACE2 activity and Ang 1-7 concentration in the striatum. Importantly, these agents induced a shift in microglial polarization from the M1 proinflammatory phenotype (marked by reduced IL-1β, iNOS, and CD86) to the M2 anti-inflammatory phenotype (marked by enhanced arginase1, Ym1, Fizz1 and CD163). This shift was associated with altered STAT signaling pathways, including decreased p-STAT1 and increased p-STAT6. Additionally, levels of miR-155 were decreased, and levels of SOCS1, MKP-1, and PP2A were increased. These findings address a critical gap in understanding how RAS modulation can influence neuroinflammation through microglial polarization via regulating the interplay between MKP-1/ miR-155 /SOCS1 and PP2A, offering a promising therapeutic strategy to mitigate neurodegeneration and inflammation in PD.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors with a crucial regulatory role in carbohydrate and lipid metabolism and are emerging druggable targets in "metabolic syndrome" (MetS) and cancers. However, there is a need to identify ligands that can activate specific PPAR subtypes, particularly PPARβ/δ, which is less studied compared with other PPAR isoforms (α and γ). Herein, using the drug-repurposing approach, the ZINC database of clinically approved drugs was screened to target the PPARβ/δ receptor through high-throughput-virtual-screening, followed by molecular docking and molecular dynamics (MD) simulation. The top-scoring ligands were subjected to drug-likeness analysis. The hit molecule was tested in an in vitro model of NAFLD (non-alcoholic fatty liver disease). The top five ligands with strong binding affinity towards PPARβ/δ were canagliflozin > empagliflozin > lumacaftor > eprosartan > dapagliflozin. RMSD/RMSF analysis demonstrated stable protein-ligand complexation (PLC) by the top-scoring ligands with PPARβ/δ. In silico ADMET prediction analysis revealed favorable pharmacokinetic profiles of these top five ligands. Canagliflozin showed significant (P < 0.001) dose-dependent decrease in lipid accumulation and the associated oxidative stress-inflammatory response, suggesting its promising anti-steatotic potential. These outcomes pave the way for further validation and development of PPAR activity-modulating therapeutics.

NMDA receptors in the prefrontal cortex (PFC) play a crucial role in cognitive functions. Previous research has indicated that angiotensin II (Ang II) affects learning and memory. This study aimed to examine how Ang II impacts NMDA receptor activity in layer V pyramidal cells of the rat PFC. Whole-cell patch-clamp experiments were performed in pyramidal cells in brain slices of 9-12-day-old rats. NMDA (30 μM) induced inward currents. Ang II (0.001-1 µM) significantly enhanced NMDA currents in about 40% of pyramidal cells. This enhancement was reversed by the AT1 antagonist eprosartan (1 µM), but not by the AT2 receptor antagonist PD 123319 (5 μM). When pyramidal neurons were synaptically isolated, the increase in NMDA currents due to Ang II was eliminated. Additionally, the dopamine D1 receptor antagonist SCH 23390 (10 μM) reversed the Ang II-induced enhancement, whereas the D2 receptor antagonist sulpiride (20 μM) had no effect. The potentiation of NMDA currents in a subpopulation of layer V pyramidal neurons by Ang II, involving AT1 receptor activation and dopaminergic signaling, may serve as an underlying mechanism for the effects of the renin-angiotensin system (RAS) elements on neuronal functions.

Lung adenocarcinoma, a disease with complex pathogenesis, high mortality and poor prognosis, is one of the subtypes of lung cancer. Hence, it is very crucial to find novel biomarkers as diagnostic and therapeutic targets for LUAD.

Eprosartan is an angiotensin receptor blocker (ARB) used for management of essential hypertension. With unique pharmacological characteristics, dual action mechanism, and clinical effectiveness, eprosartan offers additional advantages over other ARBs in specific patient populations.

Testicular torsion carries the ominous prospect of inducing acute scrotal distress and the perilous consequence of testicular atrophy, necessitating immediate surgical intervention to reinstate vital testicular perfusion, notwithstanding the paradoxical detrimental impact of reperfusion. Although no drugs have secured approval for this urgent circumstance, antioxidants emerge as promising candidates. This study aspires to illustrate the influence of eprosartan, an AT1R antagonist, on testicular torsion in rats. Wistar albino rats were meticulously separated into five groups, (n = 6): sham group, eprosartan group, testicular torsion-detorsion (T/D) group, and two groups of T/D treated with two oral doses of eprosartan (30 or 60 mg/kg). Serum testosterone, sperm analysis and histopathological examination were done to evaluate spermatogenesis. Oxidative stress markers were assessed. Bax, BCL-2, SIRT1, Nrf2, HO-1 besides cleaved caspase-3 testicular contents were estimated using ELISA or qRT-PCR. As autophagy markers, SQSTM-1/p62, Beclin-1, mTOR and AMPK were investigated. Our findings highlight that eprosartan effectively improved serum testosterone levels, testicular weight, and sperm count/motility/viability, while mitigating histological irregularities and sperm abnormalities induced by T/D. This recovery in testicular function was underpinned by the activation of the cytoprotective SIRT1/Nrf2/HO-1 axis, which curtailed testicular oxidative stress, indicated by lowering the MDA content and increasing GSH content. In terms of apoptosis, eprosartan effectively countered apoptotic processes by decreasing cleaved caspase-3 content, suppressing Bax and stimulating Bcl-2 gene expression. Simultaneously, it reactivated impaired autophagy by increasing Beclin-1 expression, decreasing the expression of SQSTM-1/p62 and modulate the phosphorylation of AMPK and mTOR proteins. Eprosartan hold promise for managing testicular dysfunction arising from testicular torsion exerting antioxidant, pro-autophagic and anti-apoptotic effect via the activation of SIRT1/Nrf2/HO-1 as well as Beclin-1/AMPK/mTOR pathways.

There has been a significant shift in the perception of hypertension as an important contributor to the global disease burden. Approximately 6 % and 8 % of pregnancies are affected by hypertension, which can adversely affect the mother and the fetus. Furthermore, a hypertensive individual is at increased risk of developing kidney disease, arterial hardening, eye damage, and strokes. Using angiotensin receptor blockers (ARBs) is widespread in treating hypertension, heart failure, coronary artery disease, and diabetic nephropathy. Despite this, some ARBs have limited use due to their poor oral bioavailability and water solubility. To tackle this, a variety of nanoparticle (NP)-based systems, such as polymeric NPs (i. e., dendrimers), polymeric micelles, polymer-drug conjugates, lipid NPs, nanoemulsions, self-emulsifying drug delivery systems (SEDDS), solid lipid NPs (SLNs), nanostructured lipid carriers (NLCs), carbon-based nanocarriers, inorganic NPs, and nanocrystals, have been recently developed for efficient delivery of losartan, Valsartan (Val), Olmesartan (OLM), Telmisartan (TEL), Candesartan, Eprosartan, Irbesartan, and Azilsartan to target cells. This review article provides a literature-based comparison of the various classes of ARBs, their mechanisms of action, and an overview of the nanoformulations developed for ARB delivery and successfully applied to managing hypertension, diabetic complications, and other conditions.