Catalytic electrodes' characterization study serving polluted water treatment: environmental healthcare and ecological risk assessment.

Pesticide residues in the environment have irreparable effects on human health and other organisms. Hence, it is necessary to treat and degrade them from polluted water. In the current work, the electrochemical removal of the fenitrothion (FT), trifluralin (TF), and chlorothalonil (CT) pesticides were performed by catalytic electrode. The characteristics of SnO2-Sb2O3, PbO2, and Bi-PbO2 electrodes were described by FE-SEM and XRD. Dynamic electrochemical techniques including cyclic voltammetry, electrochemical impedance spectroscopy, accelerated life, and linear polarization were employed to investigate the electrochemical performance of fabricated electrodes. Moreover, evaluate the risk of toxic metals release from the catalytic electrode during treatment process was investigated. The maximum degradation efficiency of 99.8, 100, and 100% for FT, TF, and CT was found under the optimal condition of FT, TF, and CT concentration 15.0 mg L-1, pH 7.0, current density 7.0 mA cm-2, and electrolysis time of 120 min. The Bi-PbO2, PbO2, and SnO2-Sb2O3 electrodes revealed the oxygen evolution potential of 2.089, 1.983, 1.914 V, and the service lifetime of 82, 144, and 323 h, respectively. The results showed that after 5.0 h of electrolysis, none of the heavy metals such as Bi, Pb, Sb, Sn, and Ti were detected in the treated solution.

Simultaneous electrochemical degradation of pesticides from the aqueous environment using Ti/SnO2-Sb2O3/PbO2/Bi electrode; process modeling and mechanism insight.

In this work, modified Bi-PbO2 electrode was fabricated and employed for simultaneous degradation of fenitrothion (FT), trifluralin (TF), and chlorothalonil (CT) from synthetic and pesticide wastewater through the anodic oxidation process. A novel high-performance liquid chromatography method was developed and optimized to identify the pesticides simultaneously. Quadratic models were developed to investigate the effects of main operating parameters and predict the degradation efficiencies of the treatment processes. The R2 of the degradation efficiencies were obtained of 0.9847, 0.9910, and 0.9821 for FT, TF, and CT, respectively, which indicates the degree of conformity between the experimental and the actual values of degradation efficiencies, and the adjusted R2 values for the degradation efficiency of FT, TF, and CT in proposed models were 0.9826, 0.9898, and 0.9796, and the values of the predicted R2 were 0.9792, 0.9875, and 0.9755, respectively. The maximum degradation efficiencies of 99.7, 100, and 100% obtained for FT, TF, and CT, respectively, under the optimal operating condition of FT, TF, and CT concentration of 10.0, 6.0, and 8.0 mg L-1, respectively, pH 6.0, the current density 6.0 mA cm-2, and electrolysis time of 60 min. Chemical oxygen demand removal and energy consumption were 64.7% and 5.1 kWh m-3. Eventually, the generated intermediates and other produced species of pesticides through the treatment process was evaluated using a gas chromatography-mass spectrometry method, and their degradation pathways were proposed.

Voltammetric approach for pharmaceutical samples analysis; simultaneous quantitative determination of resorcinol and hydroquinone.

A simple and precise analytical approach developed for single and simultaneous determination of resorcinol (RC) and hydroquinone (HQ) in pharmaceutical samples using carbon paste electrode (CPE) modified with 1-Ethyl-3-methylimidazolium tetrafluoroborate as ionic liquid and ZnFe2O4 nanoparticle. A significant enhancement in the peak current and sensitivity of the proposed sensor observed by using modifiers in the composition of working electrode compared to bare CPE which is in accordance with the results obtained from electrochemical impedance spectroscopy investigations. Electrochemical investigations revealed a well-defined irreversible oxidation peak for RC over a wide concentration range from 3.0 µM to 500 µM in 0.1 M phosphate buffer solution (pH 6.0) with the linear regression equations of Ip (µA) = 0.0276 CRC (µM) + 0.5508 (R2 = 0.997). The limit of detection and quantification for RC analysis were found to be 1.46 µM and 4.88 µM, respectively. However, the obtained SW voltammograms for simultaneous determination of RC and HQ exhibited a desirable peak separation of about 360 mV potential difference and a satisfactory linear response over the range of 50-700 µM and 5-350 µM with the favorable correlation coefficient of 0.991 and 0.995, respectively. The diffusion coefficient (D) of RC and the electron transfer coefficient (α) at the surface of ZnFe2O4/NPs/IL/CPE estimated to be 2.83 × 10- 4 cm s- 1 and 0.76. The proposed sensor as a promising and low-cost method successfully applied for determination of RC in commercial pharmaceutical formulations such as the resorcinol cream of 2% O/W emulsion available on the market with the recovery of 98.47 ± 0.04.

Leishmanicidal potentials of Gossypium hirsutum extract and its fractions on Leishmania major in a murine model: parasite burden, gene expression, and histopathological profile.

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species.Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development.Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action.Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure.Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major.Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.

Determination of trigonelline in human plasma by magnetic solid-phase extraction: a pharmacokinetic study.

Aim: To develop a novel method for the bioanalytical extraction of trigonelline (TRG) from human plasma samples using a magnetic nanocomposite and to evaluate its pharmacokinetic profile. Materials & methods: Magnetic bentonite/ß-cyclodextrine (ß-CD) nanoparticles, coupled with a validated ion-pairing reversed-phase high-performance liquid chromatography method, were used to determine TRG concentration from plasma samples following a single oral administration. Results: The developed reversed-phase high-performance liquid chromatography method was accurate, precise, specific, selective and reproducible. TRG showed rapid absorption, middle rate of elimination and mean residence time of ∼24 h. The data were best fitted on a two-compartment model in which tmax was 1.0 h, Cmax 0.115 µg/ml, area under the curve (AUC)0-24 1.72 µg/ml.h, Cl 0.0293 l/h/kg, t1/2α 0.79 h, t1/2ß 13.68 h and ka 1.63 h-1. Conclusion: The findings of this study could provide useful information to promote the future study of TRG and aid optimal dose finding.

Pharmacokinetic profile of diosgenin and trigonelline following intravenous and oral administration of fenugreek seed extract and pure compound in rabbit.

Diosgenin (DI) and trigonelline (TRG) are the main bioactive compounds of fenugreek seed. A micro-extraction method using magnetic nanocomposites coupled with ion-pairing reversed phase HPLC (RP-HPLC) method was used to determine the analytes in rabbit plasma. The main PK parameters after oral administration of pure DI and the extract were: Cmax: 0.48, 0.057 µg/ml; tmax: 1, 2 h; and t1/2ß: 6.23, 15.04 h, respectively. Pure TRG and the extract PK parameters were: Cmax: 0.121, 0.081 µg/ml; tmax: 1.30, 1.30 h; and t1/2ß: 20.06, 24.70 h, respectively. Generally, the PK profile of the two compounds was best fitted on the two-compartment model.[Formula: see text].

Simultaneous Spectrophotometric Determination of Trigonelline, Diosgenin and Nicotinic Acid in Dosage Forms Prepared from Fenugreek Seed Extract.

Mathematical algorithms offer a useful method for quantitative analysis of compounds in multi-component mixtures to overcome the overlapping problems occurred in UV spectrophotometry. The aim of this study is to develop a method for simultaneous determination of bioactive compounds in herbal dosage forms produced from fenugreek extract. A UV- spectrophotometric method based on mathematical algorithm was used to simultaneous determination of trigonelline (TRG), diosgenin (DI), and nicotinic acid (NA). The maximum absorbance (λmax) was determined to be 232.65 nm, 296.23 nm, and 262.60 nm for TRG, DI, and NA, respectively. The calibration curves showed good linearity for all analytes in the concentration range of 1-20 µg/mL (R2=0.9995, 0.9997, 0.9994 for TRG, DI and NA, respectively). The Intra- and inter-day precisions were in the range of 1.1-10.7% and 1.2-8.2%, respectively. The accuracy of the method was 96.0% for TRG, 92.9% for DI, and 104.2% for NA. The limits of detection (LOD) and quantification (LOQ) were found to be 0.91 and 3.06 µg/mL for TRG, 0.99, and 3.30 µg/mL for DI and 0.33 and 1.10 µg/mL for NA. The validated method was applied for determination of the analytes in the tablet, capsule and thin film dosage forms prepared from the fenugreek seed extract. The mean recovery percentages of the analytes were in the range of 90.0-97.4%, 85.6-105.4%, and 90.0-99.0% for tablet, capsule, and film dosage forms, respectively. Generally, the validated method could be a good candidate for routine spectrophotometric determination of the analytes without any necessity for pre-analysis extraction.

Pesticide exposure and related health problems among family members of farmworkers in southeast Iran. A case-control study.

BACKGROUND: Pesticides used in agriculture are some of the most common pollutants in the world. This study aimed to investigate the effects of Organophosphorus Pesticides (OPPs) and Organochlorine Pesticides (OCPs) on the families of farmworkers in the southeast of Iran. METHODS: In the present case-control study, 141 family members of farmworkers (as the case group) and 59 family members of non-farmworkers (as the controls) were recruited. Serum levels of OCPs such as α-HCH, ß-HCH, γ-HCH, 2,4-DDE, 4,4-DDE, 2,4-DDT, and 4,4-DDT were determined. In addition, erythrocyte acetylcholinesterase (AChE) activity, malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC), nitric oxide (NO) serum levels, arylesterase activity of paraoxonase 1 (PON-1), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity were determined in all participants. Furthermore, distance to farmlands, education, crops, type, and the number of consumed fruits were evaluated for each individual separately. RESULTS: The erythrocyte AChE activity and serum activities of GPx, SOD, and PON-1 and TAC levels were significantly decreased, whereas the concentration of MDA, PC, NO, and seven OCPs were significantly increased in the farmworkers' families as compared to the controls. Spearman correlation and linear regression suggest that OCPs increase the oxidative stress in farmworkers' family members. Moreover, distance, education, farming precedence, products, and ventilation had significant effects on the OCP levels and increased the odds ratio of OCP levels in farmworkers' families. CONCLUSION: With regards to the data obtained in this study, it was revealed that OCPs as illegal pesticides and OPPs were higher than expected in the farmworkers' family members. Furthermore, exposure to OCPs and OPPs, apart from the other effects on the body, leads to oxidative stress (OS) that may cause serious diseases in the exposed populations.

Comparing the Efficacy of Methadone and Tincture of Opium in Controlling Agitation Caused by Withdrawal Syndrome in Opium-Addicted Patients in the Intensive Care Unit: A Randomized Trial Study.

BACKGROUND: Few studies have been conducted regarding the comparison of the efficacy of methadone and tincture of opium (TOP) in controlling agitation induced by withdrawal syndrome. Therefore, the current randomized trial study is carried out with the aim to evaluate comparisons on the efficacy of methadone and TOP in controlling agitation caused by withdrawal syndrome in opium addicted patients in the intensive care units (ICUs). METHODS: This clinical trial study was conducted on 60 patients admitted to ICU of Shahid Bahonar Hospital, Kerman, Iran. After classification of the patients into two groups, the first and second groups consumed methadone syrup (5 mg/ml) and TOP (10 mg/ml), respectively. Agitation in these patients was assessed through the Richmond Agitation-Sedation Scale (RASS). Vital signs were also assessed. Paired sample t-test and independent t-test were used for data analysis. FINDINGS: In the current study, the administered dose of methadone and TOP was 36.17 ± 26.99 and 112.67 ± 102.74 mg, respectively (P < 0.010). Methadone administration led to a significant decrease of the patients' vital signs, including systolic blood pressure, heart rate, respiratory rate, and Glasgow Coma Scale (GCS) (P < 0.05). Though TOP administration decreased systolic blood pressure and GCS significantly (P < 0.05), it had no effect on patients' diastolic blood pressure, body temperature, heart rate, and respiratory rate (P > 0.05). In total, no significant difference was detected between two groups regarding vital signs (P > 0.05). However, a significant difference was seen between methadone and TOP groups in terms of RASS score (P < 0.01). CONCLUSION: According to the results of the current study, lower dose of methadone, compared to TOP, could control agitation caused by opium withdrawal symptoms.

Paclitaxel incorporated exosomes derived from glioblastoma cells: comparative study of two loading techniques.

BACKGROUND: Exosomes are natural nanoparticles that are involved in intercellular communication via transferring molecular information between cells. Recently, exosomes have been considered for exploitation as novel drug delivery systems due to their specific properties for carrying specific molecules and surface proteins. METHODS: In this study, U-87 cell derived exosomes have been investigated for delivery of a potent chemotherapeutic agent, paclitaxel (PTX). Two methods of loading were utilized to incorporate PTX in exosomes and the exosomes pharmaceutical and cytotoxic characterizations were determined. RESULTS: The drug loaded and empty exosomes were found to have particle size of 50-100 nm and zeta potential of ≈ - 20 mV. Loading capacity of 7.4 ng and 9.2 ng PTX into 1 µg of exosome total protein were also measured for incubation and sonication methods, respectively. Incorporation of PTX into exosomes significantly increased its cytotoxicity against U-87 cell line (59.92% cell viability) while it was found that the empty exosomes exhibited cell viability of 91.98%. CONCLUSIONS: Loading method could affect the loading capacity of exosomes and their encapsulated chemotherapeutic molecule showed higher cytotoxicity into exosomes. These results promise exosomes as appropriate drug delivery system for glioblastoma multiform (GBM) treatment.

Leishmanicidal, cytotoxic and apoptotic effects of Gossypium hirsutum bulb extract and its separated fractions on Leishmania major.

BACKGROUND & OBJECTIVES: Leishmaniasis is a major global health problem with no safe and effective therapeutic drugs. This study evaluated the cytotoxic and apoptotic effects of crude extract and fractions of Gossypium hirsutum bulb on Leishmania major stages using advanced experimental models. METHODS: Bulbs of G. hirsutum were collected from the Kerman province of Iran. The bulb was extracted using Soxhlet apparatus and different fractions were obtained by column chromatography (CC). Different concentrations of the extract and the fractions were evaluated against L. major and compared with Glucantime®. The cytotoxicity and apoptotic values were analysed by flow cytometry. The fractions obtained in CC were monitored by thin layer chromatography, and fractions with similar chromatographic patterns were mixed. RESULTS: The extract and two fractions, F4 and F5 inhibited the proliferation of L. major promastigotes and amastigotes in a dose-dependent manner at 72 h post-treatment. No significant cytotoxic effects were observed for extract and fractions, as the selectivity index was over 1000, far beyond >10. The mean apoptotic values for L. major were superior to those of Glucantime®. INTERPRETATION & CONCLUSION: Both the crude extract and fractions (F4 and F5) had significant antileishmanial effects on L. major stages, and were were superior relative to Glucantime®. No cytotoxic effects were associated with the extract or fractions and they showed excellent apoptotic index, a possible mechanism behind inducing parasite death. Further investigations are essential to study the effect of G. hirsutum bulb fractions in animal model and clinical settings for planning strategies for the prevention and control of leishmaniasis.

Anti-Inflammatory Subfractions Separated from Acidified Chloroform Fraction of Fenugreek Seeds (Trigonella foenum-graecum L.).

Considering the side effects of current anti-inflammatory drugs, novel therapeutic agents are desired. We have succeeded in separating flavonoid-rich fractions with anti-inflammatory effect from fenugreek seeds (Trigonella foenum-graecum L.). In this work, we aimed to carry out further fractionation to find active anti-inflammatory subfractions. Trigonelline content of the plant was determined by spectrophotometric method. Fenugreek seeds were extracted consecutively with petroleum ether, acidified chloroform (ACC), alkaline chloroform (AKC), methanol, and water. ACC fraction, which had exhibited the highest anti-inflammatory effect, was further fractionated using column chromatography. Obtained subfractions were evaluated using carrageenan-induced paw edema (CIPE) method. Animals were pretreated by test compounds, and after 30 minutes edema was induced by subcutaneous injection of 100 µl of 1% w/v carrageenan into the right paw of animals. Volume difference of both paws was measured at different times after carrageenan injection. The concentration of trigonelline was determined as 16.2%. ACC fraction inhibited paw edema significantly in comparison to control (p < .05). Four subfractions (dry weight percentage basis) were selected for pharmacological study. F3 subfraction exhibited the greatest inhibition at 15 mg/kg (p < .001). ACC fraction and F4 significantly inhibited paw edema at doses of 5, 10, and 15 mg/kg (p < .001). Phytochemical studies indicated the presence of flavonoids in ACC and active subfractions. Further separation can lead to finding active components from active subfractions, which probably belong to flavonoid phytochemicals. Considering the gastroprotective effect of fenugreek, we hope the separated fractions also would be free of gastrointestinal side effects.

A Review on Biosynthesis, Analytical Techniques, and Pharmacological Activities of Trigonelline as a Plant Alkaloid.

Trigonelline (TRG) as a polar hydrophilic alkaloid is extracted from many plant species, for example, Trigonella foenum-graecum, Allium sepapea, Coffea sp, Pissum sativum, Glycine max, and Lycopersicon esculentum. Numerous biological activities have been reported for TRG such as protection of heart and liver and treatment of hyperglycemia, hypercholesterolemia, nervous and hormonal disorders, and cancers. Thus, the aim of this review is to summarize some information about TRG's biosynthesis pathway, pharmacological activity, pharmacokinetics, and analytical techniques to introduce TRG as an alternative choice to treat the various diseases. However, current evidence is still inadequate for introducing TRG as a novel drug, and it is necessary to examine more clinical trials to determine its acute and chronic side effects, bioavailability, pharmacokinetic parameters, and mechanisms of action.

Pirfenidone protects against paraquat-induced lung injury and fibrosis in mice by modulation of inflammation, oxidative stress, and gene expression.

In this study we investigated the protective effects and possible mechanisms of pirfenidone (PF) in paraquat (PQ)-induced lung injury and fibrosis in mice. Lung injury was induced by injection of PQ (20 mg/kg). Thereafter, mice orally received water and PF (100 and 200 mg/kg) for four weeks. After 28 days, the inflammation and fibrosis were determined in the lungs by analysis of histopathology, bronchoalveolar lavage fluid (BALF) cell count, lung wet/dry weight ratio, hydroxyproline content, and oxidative stress biomarkers. Expression of several genes involved in fibrogenesis and modulation of reactive oxygen species (ROS) production, such as TGF-ß1, α-SMA, collagen Iα and IV, NOX1, NOX4, iNOS, and GPX1 were determined using RT-qPCR. PF significantly decreased the lung fibrosis and edema, inflammatory cells infiltration, TGF-ß1 concentration, and amount of hydroxyproline in the lung tissue. PF dose-dependently improved the expression level of the studied genes to the near normal. Decreasing of lung lipid peroxidation and catalase activity, and increasing of SOD activity in the treated mice were significant compared to the control group. Pirfenidone ameliorate paraquat induced lung injury and fibrosis partly through inhibition of inflammation and oxidative stress, and downregulation of genes encoding for profibrotic cytokines and enzymatic systems for ROS production.

Alkaloid and flavonoid rich fractions of fenugreek seeds (Trigonella foenum-graecum L.) with antinociceptive and anti-inflammatory effects.

The seeds of fenugreek (Trigonella foenum-graecum L.) have medicinal uses as hypoglycemic, antinociceptive and anti-inflammatory agents. We aimed to evaluate the antinociceptive and anti-inflammatory effects of the major fractions of fenugreek seeds. The methanolic extract of the plant seeds was partitioned using a liquid-liquid extraction procedure to give six major fractions. Following phytochemical screening of isolated fractions, the total extract and each fraction were evaluated for their antinociception and anti-inflammatory effects using formalin and carrageenan-induced paw edema tests respectively. The methanolic extract exhibited both antinociceptive and anti-inflammatory effects at a dose of 100mg/kg. Among the tested fractions, alkaline chloroform fraction (AKC), which was alkaloid positive in screening tests, showed the most anti-nociceptive effect in a dose-dependent manner. AKC fraction was as effective as morphine (5mg/kg) in this regard. Both aqueous and acidified chloroform fractions (ACC) could significantly inhibit paw edema at a different dose. The latter fraction dose-dependently inhibited carrageenan-induced paw edema. The results of phytochemical screening tests confirmed the presence of flavonoids in both ACC and aqueous fractions. It can be concluded that the alkaloid and flavonoid content of fenugreek seeds can be responsible for antinociception and anti-inflammatory effects of the plant respectively.

Development of a derivatisation method for the analysis of aldehyde modified amino acid residues in proteins by Fourier transform mass spectrometry.

A method was developed for the analysis of amino acids within bovine serum albumin (BSA) which had been modified by reaction with different enals. BSA was reacted with the aldehydes and the reaction products were stabilised by reaction with NaBH(4). The protein was then hydrolysed with 6N HCl and the hydrolysis products were analysed by liquid chromatography-mass spectrometry (LC-MS). The modified amino acids were derivatised with propylchloroformate. High resolution mass spectrometry carried out using an LTQ-Orbitrap instrument which was able to characterise a wide range of adducts. In addition double adducts were observed to be formed with 4-hydroxynonenal (HNE) and lysine or lysine+histidine. Qualitatively it was possible to consistently observe a pyridinium adduct formed between lysine and pentenal in human plasma from normal subjects.