Nephroprotective Effect of Bergapten Against Cyclophosphamide-Mediated Renal Stress, Inflammation, and Fibrosis in Wistar Rats: Probable Role of NF-kB and TGF-ß1 Signaling Molecules.

Cyclophosphamide (CPM) is a well-established antineoplastic drug with marked clinical outcomes in various types of cancers. Despite being a promising drug, its use is associated with significant renal toxicity and often limits its use, leading to compromised clinical outcomes. Therefore, this study explored the renal protective effect of bergapten (BGP), a natural bioactive compound that showed marked antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Till now, BGP has not been studied for its renal protective effect in an in vivo model. Animals were divided into control, toxic, BGP-3, BGP-10, and BGP Per se. The control group was treated with normal saline for 2 weeks. To the toxic group, CPM 200 mg/kg was given on day 7 as i.p. To BGP-3, 10, and Per se, BGP-3 and 10 mg/kg, ip was given 2 weeks with a single shot of CPM 200 day 7. To the Per se group, only BGP 10 mg/kg, ip was given from day 1 to day 14. After 14 days, animals were sacrificed, and kidneys were removed and studied for the markers of oxidative stress, inflammation, renal injury, renal fibrosis, and renal damage using biochemical, histopathological, and immunohistochemical studies. We found that BGP-10 effectively reversed the damage toward normal, whereas BGP-3 failed to exhibit a significant renal protective effect. We conclude that bergapten could be a potential renal protective drug, and hence, more detailed cellular molecular-based studies are needed to bring this drug from the bench to the bedside.

Sonochemical synthesis of lanthanum ferrite nanoparticle-decorated carbon nanotubes for simultaneous electrochemical determination of acetaminophen and dopamine.

A new nanocomposite consisting of lanthanum ferrite nanoparticles (LaFeO3 NPs) integrated with carbon nanotubes (CNTs) was fabricated via facile sonochemical approach. The engineered nanocomposite was applied to simultaneously determine acetaminophen (ACP) and dopamine (DA) in a binary mixture. The LaFeO3 NPs@CNT probe possesses several advantages such as superior conductivity, large surface area, and more active sites, improving its electrocatalytic activity towards ACP and DA. Under optimized conditions, the anodic peak currents (Ipa) linearly increased with increasing concentration of ACP and DA in the range 0.069-210 µM and 0.15-210 µM, respectively. The sensitivity of LaFeO3 NPs@CNTs/glassy carbon electrode (GCE) for detecting ACP and DA is 7.456 and 5.980 µA·µM-1·cm-2, respectively. The detection limits (S/N = 3) for ACP and DA are 0.02 µM and 0.05 µM, respectively. Advantages of LaFeO3 NPs@CNTs/GCE for the detection of ACP and DA include wide linear ranges, low-detection limits, good selectivity, and long-term stability. The as-fabricated electrode was applied to determine ACP and DA in pharmaceutical formulations and human serum samples with recoveries ranging from 97.7 to 103.3% and an RSD that did not exceed 3.7%, confirming the suitability of the proposed sensor for the determination of ACP and DA in real samples. This study not only presents promising opportunities for enhancing the sensitivity and stability of electrochemical sensors used in the detection of bioanalytes but also significantly contributes to the progress of unique and comprehensive biochemical detection methodologies.

Selective detection of rutin at novel pyridinic-nitrogen-rich carbon dots derived from chicken feet biowaste: The role of bovine serum albumin during the assay.

A simple fluorescence method is described for measuring rutin dependent on the nitogen-doped carbon dots (NCDs) prepared via simple pyrolysis method from chicken feet biowaste. The as-fabricated NCDs have unique advantages including cost-effectiveness and high quantum yield (42.9 %). The as-prepared NCDs explore an optimal emission band at 430 nm following exciting NCDs at 330 nm. Addition of rutin to blue-emissive NCDs quenched their fluorescence emission by inner-filtration effect (IFE) and static quenching. Under optimized conditions, the fluorescence responses increased as the rutin amount was raised from 100 to 1000 nmol/L with 5.3 nmol/L as a detection limit (S/N = 3). The probe selectivity was improved by adding bovine serum albumin (BSA), which binds other structurally-related compounds (other flavonoids). The as-synthesized NCDs exhibited some advantages towards rutin detection such as: lower LOD value, satisfactorily reproducibility, simplicity, rapidity, selectivity, and stability. The sensing probe was efficiently utilized for determining rutin in different real samples with acceptable results. The sensor offers an efficient biowaste-based approach for the determination of (bio) molecules.

Enhanced antinociceptive activity of Nigella sativa oil after its combined treatment with honey in rats.

Antinociceptive activity of honey and Nigella sativa (N. sativa) oil are well known. Therefore, aim of this study was to investigate the antinociceptive effect of N. sativa oil and its concurrent administration with honey in rats. The tested animals were randomized into 5 groups: Group (1) Normal saline (0.2ml, p.o.); Group (2) N. sativa oil (1gm/kg, p.o.); Group (3) honey (1gm/kg, p.o.); Group (4) N. sativa oil (1gm/kg, p.o.) + honey (1gm/kg, p.o.): Group (5) pethidine (20mg/kg, S.C.) as positive standard. The antinociceptive activity was tested using radiant heat and tail immersion tests. Antioxidant potential was determined by using in-vitro antioxidant assays. Our findings showed that N. sativa oil and honey have antinociceptive effect, the antinociceptive effect appeared after 30 and 60min of administration and declined after 120 and 180 min. Combined administration of N. sativa oil with Honey increased the antinociceptive effect by 20 to 30% in all models. In addition, the antinociceptive effect of the combination reduced the time for onset of action as well as prolonged its duration of action. In conclusion, combined treatment of N. sativa oil with honey increased its antinociceptive activity, showed faster onset of action and prolonged its duration, the fact that can be utilized in the management of painful conditions in humans.

Highly selective and sensitive electrochemical determination of cysteine based on complexation with gold nanoparticle-modified copper-based metal organic frameworks.

A gold nanoparticle-modified copper-based metal organic framework (Au NPs@Cu-BDC) was fabricated for the electrochemical determination of cysteine (Cys-SH). The nanocomposites were characterized using different techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), powder X-ray spectroscopy (PXRD), thermogravimetry (TGA), nitrogen adsorption-desorption isotherms, and Fourier transform infrared spectroscopy (FTIR). Formation of a new anodic peak of Cu(II)-Cys complex at + 0.43 V was used to detect Cys-SH. Cyclic and square wave voltammetric studies proved that the Au NPs enhanced the conductivity of Cu-BDC. The proposed electrode exhibited a linear range of 0.0015-10.5 µM and low detection limit of 0.0004 µM with a good sensitivity of 0.78 ± 0.01 µA µM. The as-fabricated electrode was successfully used for the estimation of Cys-SH in real samples (human plasma, urine, and saliva) with recovery % of 99-100% and RSD % of 2.7-3.6%, respectively.

Umbelliferone ameliorates ulcerative colitis induced by acetic acid via modulation of TLR4/NF-κB-p65/iNOS and SIRT1/PPARγ signaling pathways in rats.

Ulcerative colitis (UC) is a common chronic, idiopathic inflammatory bowel disease associated with inflammatory perturbation and oxidative stress. Umbelliferone (UMB) is a potent anti-inflammatory and antioxidant coumarin derivative. Depending on the possible mechanisms, we aimed to explore and elucidate the therapeutic potential of UMB on UC-inflammatory response and oxidative injury-induced via intrarectal administration of acetic acid (AA) in rats. Animals were assigned into four groups: control group, UMB (30 mg/kg, oral)-treated group, AA-induced colitis model group (2 ml of AA; 3% v/v), and colitis treated with UMB group. The results showed that UMB improved macroscopic and histological tissue injury caused by the AA. Mechanistically, UMB reduced the elevated colonic TNF-α, IL-6, MPO, and VCAM-1 and downregulated the gene and protein expression of TLR4, NF-κB, and iNOS signaling factors, exhibiting potent anti-inflammatory effects. Moreover, UMB upregulated the gene and protein expression of both SIRT1 and PPARγ signaling pathways, thereby inhibiting both oxidative injury and inflammatory response. Conclusively, UMB protected rats against AA-induced UC by suppressing the TLR4/NF-κB-p65/iNOS signaling pathway and promoting the SIRT1/PPARγ signaling. Our results showed the effectiveness of UMB in alleviating the pathogenesis of UC and introduced it as a possible therapeutic applicant for clinical application.

Evaluation of the Potential of National Sharing of a Unified Progress Test Among Colleges of Pharmacy in the Kingdom of Saudi Arabia.

BACKGROUND: With the expansion in pharmacy education in Saudi Arabia, there is a pressing need to maintain quality assurance in pharmacy programs using several tools. The progress test is a formative assessment tool that can serve to provide information to all stakeholders. This study evaluated the results of a unified progress test that was shared among 15 colleges of pharmacy. METHODS: The progress test was composed of 100 MCQs where 30% of which cover basic pharmaceutical sciences and 70% cover pharmacy practice. The questions were collected from all the 15 colleges of pharmacy participated in the test. The test was administered online to all undergraduate students in the professional programs of these colleges. RESULTS: The overall attendance rate was 80% from the total number of students enrolled in the participating colleges. Mean scores of students in basic pharmaceutical sciences were relatively higher than in pharmacy practice. The assessment results of the students in the unified program learning outcomes among colleges were higher in the domains of knowledge and skills compared to competence domain. There was a significant increment in the mean scores of the students as they progress through the years of the professional program. No correlation was found between the mean scores in the test and the cumulative grade point average (cGPA) of all students regardless of their level. CONCLUSION: The results indicated growth and maintenance of the gained knowledge and skills by the students as they progress through the years of the professional program with consistency in the results among the participating colleges. Sharing a unified test was effective as a valuable tool for the colleges of pharmacy for the purposes of benchmarking and improving the curricula. In addition, it could serve to evaluate learning of students and harmonize knowledge and skills gained by students at different institutions.

Dispensing Practices for Weight Management Products in Eastern Saudi Arabia: A Survey of Community Pharmacists.

Due to changing lifestyles and socioeconomic status, obesity prevalence has been rising in Saudi Arabia, and community pharmacists often counsel patients about its management. The study aimed to evaluate practices of community pharmacists involved in dispensing products for weight control in four cities located in the eastern province of Saudi Arabia. A cross-sectional study was conducted involving community pharmacists in Dammam, Dhahran, Khobar, and Al-Ahsa, using a Likert format questionnaire. Only those who consented to participate were handed the questionnaire. A total of 100 complete responses were analyzed. The median value for packs sold per month for tea containing products Al-Diafa Slimming Tea, Jamue Tea, and Green Tea was ≥6 while the same for orlistat and apple cider vinegar were ≤4. Moreover, >50% of pharmacists mentioned that orlistat and apple cider vinegar were effective while ≥35% mentioned that metformin and Jamue tea were effective. Furthermore, ≥25% mentioned that green tea and Al-Diafa slimming tea were effective. Excluding orlistat, >50% of pharmacists did not know about adverse effects for other products. The rate of dispensing of several weight loss products was significant for participants' background characteristics, such as time duration of consultation, gender, and age of patients, and pharmacist work experience (p < 0.05). The tea products and orlistat were the most frequently sold products, and community pharmacists appeared most knowledgeable about the effectiveness and adverse effect of orlistat. The pharmacists seemed to be aware about the effectiveness of other weight loss products; however, their knowledge about their potential adverse effects was unsatisfactory.

NiFe2O4 nanospheres functionalized with 2-(2, 4-Dihydroxyphenyl)-3, 5, 7-trihydroxychromen-4-one for selective solid-phase microextraction of aluminium.

Herein, a rational combination of dispersive solid-phase sorbent and 2-(2, 4-Dihydroxyphenyl)-3, 5, 7-trihydroxychromen-4-one (morin) was proposed for sensitive and selective determination of Al3+ ion. Nickel ferrite nanospheres (NiFe2O4 NS) functionalized with morin was used to preconcentrate and estimate Al3+ via the formation of fluorescent complex at pH 7.0. The functionalization was assisted by anionic surfactant sodium dodecyl sulphate (SDS) and ultrasonication. The results revealed that the fluorescence intensity of Al-morin/SDS@ NiFe2O4 NS is higher than Al-morin. Functionalization of NiFe2O4 NS with morin was confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometer (PXRD), and fluorescence spectroscopy. Under the optimum conditions, the fluorescence intensity increased with increasing of Al3+ concentrations in the range of 0.28-500.0 ng mL-1 with LOD (S/N = 3) of 0.09 ng mL-1. The method was applied for the determination of Al3+ in natural waters and human serum samples with recoveries % of 97-104% and RSDs % of 2-4%.

Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics.

OBJECTIVES: To determine the influence of caffeine on pharmacokinetics and pharmacodynamics of pioglitazone (PIO) in diabetic rats. METHODS: This was a preclinical study conducted in the College of Pharmacy, Najran University, Saudi Arabia, using 5 groups of Wistar rats: normal rats, untreated diabetic rats, diabetic rats + caffeine (20 mg/kg), diabetic rats + PIO (10 mg/kg), and diabetic rats + PIO (10 mg/kg) + caffeine (20 mg/kg). The drugs were administered for 14 days, and fasting plasma glucose concentrations were determined on the first day, and thereafter at weekly intervals. On day 14, rat sacrifice was followed with assay of levels of biomarkers. To estimate the pharmacokinetic parameters, the diabetic animals were assigned to 2 groups: one group received PIO (10 mg/kg), while the other received PIO + caffeine (20 mg/kg). Blood samples were drawn from the retro-orbital plexus at different time intervals, and pharmacokinetic parameters were measured using high performance liquid chromatography. RESULTS: Caffeine caused statistically marked increases in area under the curve, Cmax, Tmax, and half-life of PIO, and decreased clearance. Combination of PIO and caffeine produced a synergistic effect on percentage reduction in blood glucose, with 67.1% reductions observed on day 7 and 68.9% reductions observed on day 14. Liver and cardiac biomarkers were significantly decreased, suggesting cardioprotective and hepatoprotective effects. CONCLUSION: Co-administration of PIO with caffeine enhances its antidiabetic effect, probably due to enhanced bioavailability of PIO, leading to clinical benefits in diabetic patients.

Facile one pot sonochemical synthesis of layered nanostructure of ZnS NPs/rGO nanosheets for simultaneous analysis of daclatasvir and hydroxychloroquine.

In this study, zinc sulfide nanoparticles were loaded on reduced graphene oxide (ZnS NPs/rGO) using simple sonochemical method. The nanocomposite was characterized using different morphological and electrochemical techniques such as TEM, SEM, PXRD, EDX, Raman spectroscopy, FTIR, N2-adsorption-desorption, CV, and EIS. The ZnS NPs/rGO modified glassy carbon electrode (GCE) was used to simultaneously estimate hydroxychloroquine (HCQ) and daclatasvir (DAC) in a binary mixture for the first time. The modified nanocomposite exhibited good catalytic activity towards HCQ and DAC detection. In addition, it showed higher sensitivity, good selectivity and stability; and high reproducibility towards HCQ and DAC analysis. The activity of the modified electrode was noticeably improved due to synergism between ZnS NPs and rGO. Under optimum conditions of DPV measurements, the anodic peak currents (Ipa) were obviously increased with the increase of HCQ and DAC amounts with linear ranges of 5.0-65.0 and 7.0-65.0 nM with LODs of 0.456 and 0.498 nM for HCQ and DAC, respectively. The ZnS NPs/ rGO modified GCE was used to quantify HCQ and DAC in biological fluids with recoveries of 98.7-102.7% and 96.9-104.5% and RSDs of 1.89-3.57% and 1.91-3.70%, respectively.

Design of "Turn On" fluorometric nanoprobe based on nitrogen doped graphene quantum dots modified with ß-cyclodextrin and vitamin B6 cofactor for selective sensing of dopamine in human serum.

Herein, a novel and rapid fluorometric nanoprobe was constructed for quantitation of dopamine (DA) in presence of biologically interfering compounds. The nanoprobe based on synthesis of yellow emissive nitrogen doped graphene quantum dots (N@GQDs) by advanced thermal driven oxidation. After that, the synthesized N@GQDs was capped with ß-cyclodextrin (ß-CD), followed by interaction with pyridoxal (PYL) vitamin B6 cofactor. This interaction resulted in diminishing the yellow fluorescence of ß-CD/N@GQDs, and appearance of blue emission peak at 420 nm. Upon addition of DA, the blue emission of ß-CD/N@GQDs was increased after excitation at λ = 330 nm. Under optimum conditions, the nanoprobe exhibited a linear range of 0.36-400 nM with limit of detection (LOD) of 0.117 nM. In addition, the fluorescent nanoprobe shows high selectivity and can be used for detection of DA in complicated biological matrices and human serum. This strategy might provide a potential tool for clinical diagnosis and biomedical research for DA related diseases.

Nitrogen and sulfur co-doped graphene quantum dots/nanocellulose nanohybrid for electrochemical sensing of anti-schizophrenic drug olanzapine in pharmaceuticals and human biological fluids.

A nanohybrid prepared from green source (nanocellulose, NC) and nitrogen, sulfur co-doped graphene quantum dots (N, S@GQDs) was prepared for the electrochemical detection of olanzapine (OLZ), atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. Polar groups on the surface of NC and N, S@GQDs provide more anchoring sites for adsorption of OLZ onto the electrode surface. In addition, it provides high conductivity, good mechanical strength, large surface area, and excellent electrical conductivity. The nanocomposite was characterized morphologically and electrochemically by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDX), transmission electron microscope (TEM), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave adsorptive stripping voltammetry (SWAdSV). Under the optimized conditions, the modified electrode has a good response in the range of 1.5-90.0 × 10-8 M with LOD of 0.5 × 10-8 M. The proposed electrode offers high sensitivity, selectivity, and reliability towards OLZ detection. The SWAdSV was used to determine OLZ in pharmaceutical tablets, human plasma and urine with good recoveries % and reasonable RSD% values.

Dual-recognition molecularly imprinted aptasensor based on gold nanoparticles decorated carboxylated carbon nanotubes for highly selective and sensitive determination of histamine in different matrices.

In this study, an electrochemical aptamer based sensor (aptasensor) was proposed for specific recognition of histamine (HIS). The electrochemical aptasensor based on fabrication of glassy carbon electrode (GCE) with molecular imprinted polymer (MIP) and DNA aptamers on gold nanoparticles (AuNPs) and carboxylated carbon nanotubes (cCNTs) (MIP-apta/AuNPs/cCNTs/GCE). The aptasensor exhibits high selectivity towards HIS detection as it has two recognition elements which are MIP cavities and aptamer interaction. Upon exposure of MIP-apt/AuNPs/cCNTs/GCE to HIS, the current of redox probe was decreased that depends on the template (HIS) concentration. The effects of aptamer concentration, incubation time, pH and AuNPs electro-deposition time were optimized. Differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques were used to analyze HIS in complicated matrices. Favorable performance of MIP-apt/AuNPs/cCNTs/GCE was achieved with linearity ranges of 0.46-35 nmol L-1 and 0.35-35 nmol L-1 with limits of detection (LODs, S/N = 3) of 0.15 nmol L-1 and 0.11 nmol L-1 using DPV and EIS, respectively. The fabricated aptasensor displayed high selectivity, desirable reproducibility and stability. The MIP-apt/AuNPs/cCNTs/GCE was used to detect HIS in human plasma and canned tuna samples with good recoveries % and RSDs %.

Silver nanoparticles conjugated MnFe-based Prussian blue analogue for voltammetric and impedimetric bioaptasensing of amifostine (ethyol).

A novel bioaptasensing-based electrochemical method for determination of amifostine (AMF) is proposed. The electrochemical aptasensor is based on modification of a glassy carbon electrode with a nanocomposite consisting of silver nanoparticles @ MnFe Prussian blue analogue nanospheres (AgNPs@MnFePBA NS), followed by immobilization of aptamer via Ag-N bonds (aptamer/AgNPs@MnFePBA NS/GCE). Experimental parameters including pH, incubation time, and aptamer concentrations were optimized. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetric (DPV) techniques were utilized to quantify AMF. The anodic peak current (∆Ipa) and charge transfer resistance (∆Rct) differences increase in the presence of AMF. Under the optimal conditions, using the redox probe, the electrochemical aptasensor exhibited linear ranges of 0.34-45 nmol L-1 and 0.69-45 nmol L-1 with LODs of 0.11 nmol L-1 and 0.23 nmol L-1 for EIS and DPV, respectively. The aptasensor was used to determine AMF in human plasma and in the presence of interfering species with recoveries and RSDs in the range 97.8-103.2% and 2.2-4.2%, respectively. Graphical abstract.

Hepatoprotective effect of rebamipide against methotrexate-induced hepatic intoxication: role of Nrf2/GSK-3ß, NF-κß-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2 signaling pathways.

OBJECTIVES: The fact that methotrexate (MTX) is hepatotoxic is an important reason to limit its clinical use. Rebamipide (REB) has antioxidant and anti-inflammatory properties and is useful for the treatment of gastro-duodenal ulcers. This study investigated the impact and protective mechanisms of REB against MTX-induced hepatotoxicity in rats. MATERIALS AND METHODS: Animals were divided into four groups of six rats each: a control group, REB group (REB 100 mg/kg/day, orally), MTX control group (20 mg/kg, single i.p.), and MTX + REB group. RESULTS: The administration of MTX induced marked hepatic injury in the form of hepatocyte inflammatory swelling, degeneration, apoptosis, and focal necrosis. In parallel, our biochemical investigations revealed a marked hepatic dysfunction associated with the disturbance of the oxidant/antioxidant balance in the group treated with only MTX. Moreover, MTX led to the down-regulation of the hepatic Nrf2 and Bcl-2 expressions along with a marked elevation in the hepatic NF-κß-p65, GSK-3ß, JAK1, STAT3, PUMA, and Bax expressions. On the other hand, co-treatment with REB significantly ameliorated the aforementioned histopathological, biochemical, and molecular defects caused by MTX treatment. CONCLUSION: the outcomes of the present study showed REB's ability to protect from hepatic injury induced by MTX, possibly through its antioxidant, anti-inflammatory, and anti-apoptotic properties. These effects could be attributed to REB's ability to modulate, at least in part, the Nrf2/GSK-3ß,NF-κß-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2signaling pathways.

A novel imidazole derived colorimetric and fluorometric chemosensor for bifunctional detection of copper (II) and sulphide ions in environmental water samples.

Herein, a novel "ON-OFF" colorimetric and fluorometric chemosensor; 1N-allyl-2-(2, 5-dimethoxyphenyl)-4, 5-diphenyl-1H-imidazole (ADPPI), was constructed for sequential determination of Cu2+ and S2- ions in aqueous media. The interaction between chemosensor ADPPI and different metal cations was investigated using UV-VIS and fluorimetric spectroscopy. ADPPI showed a favorable and good interaction with Cu2+ ions producing blue colored solution peaked at 610 nm with blue fluorescence at λem. = 447 nm. The produced complex between Cu2+ ions and ADPPI can be used as a cascade probe for detection of S2- ions. The detection limits (LODs) were 1.01 nM and 1.25 µM for Cu2+ and S2- ions, respectively (the lowest between the family of colorimetric and fluorometric chemosensors). To further increase the applicability of the proposed method, Cu2+ and S2- ions concentrations were measured in environmental water samples.