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A disturbance in redox balance has been implicated in the pathogenesis of a number of diseases. This study sought to examine the feasibility of imaging brain redox status using a 11 C-labeled dihydroquinoline derivative ([ 11 C]DHQ1) for positron emission tomography (PET). The lipophilic PET tracer [ 11 C]DHQ1 was rapidly oxidized to its hydrophilic form in mouse brain homogenate. The redox modulators diphenyleneiodonium and apocynin significantly reduced the initial velocity of [ 11 C]DHQ1 oxidation, and apocynin also caused concentration-dependent inhibition of the initial velocity. Moreover, [ 11 C]DHQ1 readily entered the brain by diffusion after administration and underwent oxidation into the hydrophilic cationic form, which then slowly decreased. By contrast, apocynin treatment inhibited the in vivo oxidation of [ 11 C]DHQ1 to the hydrophilic cationic form, leading to a rapid decrease of radioactivity in the brain. Thus, the difference in the [ 11 C]DHQ1 kinetics reflects the alteration in redox status caused by apocynin. In conclusion, [ 11 C]DHQ1 is a potential PET tracer for imaging of redox status in the living brain.

Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here.  COS-nanoparticles (NP ) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. The selected NP formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NP provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies.  In conclusion, APO-loaded COS-NP could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.

Ciprofloxacin (CFX), a fluoroquinolone antibiotic, is known to induce oxidative stress–mediated cardiotoxicity. This study investigates the potential protective and therapeutic effects of apocynin (APO), a selective NADPH oxidase (NOX) inhibitor and potent antioxidant, against CFX-induced myocardial injury in rats. Thirty-two male Wistar albino rats were randomly divided into four groups ( n  = 8). CFX (25 mg/kg, i.p.) was administered twice daily for one week, while APO (20 mg/kg, i.p.) was given once daily for four days either before or after CFX treatment. Hemodynamic parameters (heart rate, systolic, diastolic, and mean blood pressures) and electrocardiographic (ECG) indices (PR, QRS, and QT intervals) were recorded invasively. Histopathological evaluations assessed myocardial inflammation, cardiomyocyte degeneration, and aortic intima–media thickness. Biochemical analyses of cardiac and aortic tissues included measurements of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels. CFX administration significantly elevated cardiac MDA by ~ 45% and decreased SOD and CAT activities by ~ 30–35% ( p  < 0.05) compared with controls. These alterations were markedly attenuated in APO-treated rats, where antioxidant enzyme activities increased by ~ 25–40% and MDA levels were restored toward normal values ( p  < 0.05 vs. CFX). APO also shortened the QT interval by ~ 15% and improved systolic pressure by ~ 12% compared with the CFX group ( p  < 0.05). Histopathological findings confirmed reduced myocardial degeneration and inflammatory infiltration in both APO + CFX and CFX + APO groups. APO effectively ameliorated CFX-induced cardiac oxidative injury by inhibiting NOX2-mediated reactive oxygen species formation and restoring antioxidant defense mechanisms, leading to functional improvement in ECG and hemodynamic parameters. These results suggest that targeted NOX inhibition may represent a practical pharmacological approach to reduce fluoroquinolone-associated cardiotoxicity, warranting further translational investigation.

Steroid‐induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast apoptosis and osteogenic differentiation dysfunction caused by GC‐induced oxidative stress and mitochondrial impairment are strongly implicated in SIFHN. Apocynin (APO) is a kind of acetophenone extracted from an herb. In recent years, APO has received much attention for its antiapoptotic and antioxidant properties. This study aimed to investigate whether APO could protect against SIFHN and explore the mechanism. In our study, low‐dose APO had no toxic effects on osteoblasts and restored dexamethasone (Dex)‐treated osteoblasts by improving survival, inhibiting OS and restoring mitochondrial dysfunction. Mechanistically, APO alleviated Dex‐induced osteoblast injury by activating the Nrf2 pathway, and the use of ML385 to block Nrf2 significantly eliminated the protective effect of APO. In addition, APO could reduce the formation of empty lacunae, restore bone mass and promote the expression of Nrf2 in SIFHN rats. In conclusion, APO protects osteoblasts from Dex‐induced oxidative stress and mitochondrial dysfunction through activation of the Nrf2 pathway and may be a beneficial drug for the treatment of SIFHN.

Aims/hypothesisIn the context of diabetes, the health benefit of antioxidant treatment has been widely debated. In this study, we investigated the effect of antioxidant treatment during the development of insulin resistance and hyperphagia in obesity and partial lipodystrophy.MethodsWe studied the role of antioxidants in the regulation of insulin resistance using the tamoxifen-inducible fat-specific insulin receptor knockout (iFIRKO) mouse model, which allowed us to analyse the antioxidant’s effect in a time-resolved manner. In addition, leptin-deficient ob/ob mice were used as a hyperphagic, chronically obese and diabetic mouse model to validate the beneficial effect of antioxidants on metabolism.ResultsAcute induction of insulin receptor knockout in adipocytes changed the substrate preference to fat before induction of a diabetic phenotype including hyperinsulinaemia and hyperglycaemia. In healthy chow-fed animals as well as in morbidly obese mice, this diabetic phase could be reversed within a few weeks. Furthermore, after the induction of insulin receptor knockout in mature adipocytes, iFIRKO mice were protected from subsequent obesity development through high-fat diet feeding. By genetic tracing we show that the persistent fat mass loss in mice after insulin receptor knockout in adipocytes is not caused by the depletion of adipocytes. Treatment of iFIRKO mice with antioxidants postponed and reduced hyperglycaemia by increasing insulin sensitivity. In ob/ob mice, antioxidants rescued both hyperglycaemia and hyperphagia.Conclusions/interpretationWe conclude that fat mass reduction through insulin resistance in adipocytes is not reversible. Furthermore, it seems unlikely that adipocytes undergo apoptosis during the process of extreme lipolysis, as a consequence of insulin resistance. Antioxidants have a beneficial health effect not only during the acute phase of diabetes development, but also in a temporary fashion once chronic obesity and diabetes have been established.

Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (2 3 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases.

Alzheimer’s disease (AD) is one of the most complicated neurodegenerative diseases, and several hypotheses have been associated with its development and progression, such as those involving glucose hypometabolism, the cholinergic system, calcium imbalance, inflammation, oxidative imbalance, microtubule instability, and the amyloid cascade, several of which are related to oxidative stress (free radical generation), which contributes to neuronal death. Therefore, several efforts have been made to establish a sporadic AD model that takes into account these hypotheses. One model that replicates the increase in amyloid beta (Aβ) and oxidative stress in vivo is the scopolamine model. In the present work, the chronic administration (6 weeks) of scopolamine was used to analyze the neuroprotective effects of apocynin and galantamine. The results showed that scopolamine induced cognitive impairment, which was evaluated 24 h after the final dose was administered. In addition, after scopolamine administration, the Aβ and superoxide anion levels were increased, and NADPH oxidase 2 (NOX2), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa B (NFkB) genes were overexpressed. These effects were not observed when either apocynin or galantamine was administered during the last 3 weeks of scopolamine treatment, and although the results from both molecules were related to lower Aβ production and, consequently, lower superoxide anion production, they were likely realized through different pathways. That is, both apocynin and galantamine diminished NADPH oxidase expression, but their effects on transcription factor expression differed. Moreover, experiments in silico showed that galantamine did not interact with the active site of beta secretase, whereas diapocynin, an apocynin metabolite, interacted with the beta-site APP-cleaving enzyme (BACE1) at the catalytic site.

Tacrolimus (FK506) is a potent immunosuppressive agent widely employed to prevent allogeneic rejection in transplant recipients. However, its nephrotoxic effects pose significant limitations to long-term therapeutic use. To address this challenge, the present study aims to develop an innovative oral nano-delivery system designed to mitigate FK506-induced nephrotoxicity through the antioxidant properties of Apocynin (APO), clove oil (CO), and chitin oligosaccharide (CTOS). A nanostructured lipid carrier (NSLC) incorporating APO dissolved in CO and functionalized with CTOS was formulated using ultrasonic emulsification. Gelucire 43/01 and CO served as key lipid components in varying ratios. Physicochemical characterization of the developed NSLCs was conducted, assessing particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%). The optimized formulation (F4) exhibited an EE% of 63.85 ± 1.98, PS of 123 ± 2.21 nm, PDI of 0.17 ± 0.09, and ZP of − 28 ± 1.98, demonstrating a biphasic release profile and stability under refrigerated conditions for six months. In vivo nephroprotective efficacy was evaluated in FK506-induced acute kidney injury (AKI) rat models, where oral administration of APO-loaded NSLCs significantly improved renal function and alleviated nephrotoxicity, as evidenced by biochemical markers and histopathological analyses. These findings underscore the potential of APO-loaded NSLCs as a promising oral phytopharmaceutical strategy for mitigating FK506-associated nephrotoxicity and enhancing therapeutic outcomes in transplant patients. Further studies are warranted to optimize and expand clinical applications.

Organophosphates (OPs) are potent anti-acetylcholinesterase compounds historically used as pesticides and exploited in chemical warfare. Exposure to OPs initiates cholinergic crisis with both peripheral and central effects such as salivation, lacrimation, urination, and defecation (SLUD), and status epilepticus (SE), a prolonged state of seizure. Standard medical countermeasures atropine, oximes, and benzodiazepines reduce mortality, control peripheral symptoms, and terminate SE. However, they do not attenuate the consequences of SE, including neurodegeneration, oxidative stress, neuroinflammation, epilepsy, and associated comorbidities such as cognitive dysfunction. SE induces excessive NADPH oxidase (NOX) synthesis and production of reactive oxygen species, which is a key driver of neurodegeneration and epilepsy. Furthermore, inhibition of NOX in SE-induced epilepsy models reduces neuroinflammation, neurodegeneration, and seizure frequency. Following OP toxicity, treatment with NOX inhibitors diapocynin and mitoapocynin reduced oxidative stress and astrocyte reactivity. This review summarizes the history and development of OPs and the current knowledge on OP toxicity, emphasizing the role of NOX, and the therapeutic potential of NOX inhibitors in treating long-term consequences of acute exposure to OPs.

In this study, the voltammetric behavior of apocynin on a boron-doped diamond electrode in a phosphate buffer (pH 7.3) has been reported for the first time. The oxidation process is quasi-reversible, diffusion-controlled, and involves one electron and one proton. The product of the electrode reaction is an unstable radical that undergoes successive chemical transformations near the working electrode. The proposed mechanism of this process can be described as EqCi and served as the basis for the development of a new voltammetric method for determining apocynin in natural samples. The analytical signal was the anodic peak on DPV curves at a potential of 0.605 V vs. Ag/AgCl. A linear response was observed in the concentration range of 0.213–27.08 mg L−1. The estimated LOD and LOQ values were 0.071 and 0.213 mg L−1, respectively. The effectiveness of the method was demonstrated both in control determinations and in the analysis of the dietary supplement. This procedure is simple, fast, sensitive, selective, and requires no complicated sample preparation, which is limited only to a simple extraction with ethanol. The low consumption of non-toxic reagents makes it environmentally friendly. To the best of our knowledge, this is the first presentation of a voltammetric procedure to determine this analyte studied in a phosphate buffer solution on a boron-doped diamond electrode. It can also be easily adapted to determine other phenolic compounds with antioxidant properties in various matrices.