Electrophysiological and molecular mechanisms of protection by iron sucrose against phosphine-induced cardiotoxicity: A time course study

The present study was designed for determining the exact mechanism of cytotoxic action of aluminum phosphide (AlP) in the presence of iron sucrose as the proposed antidote. Rats received AlP (12 mg/kg) and iron sucrose (5-30 mg/kg) in various sets and were connected to cardiovascular monitoring device. After identification of optimum doses of AlP and iron sucrose, rats taken in 18 groups received AlP (6 mg/kg) and iron sucrose (10 mg/kg), treated at six different time points, and then their hearts were surgically removed and used for evaluating a series of mitochondrial parameters, including cell lipid peroxidation, antioxidant power, mitochondrial complex activity, ADP/ATP ratio and process of apoptosis. ECG changes of AlP poisoning, including QRS, QT, P-R, ST, BP and HR were ameliorated by iron sucrose (10 mg/kg) treatment. AlP initiated its toxicity in the heart mitochondria through reducing mitochondrial complexes (II, IV and V), which was followed by increasing lipid peroxidation and the ADP/ATP ratio and declining mitochondrial membrane integrity that ultimately resulted in cell death. AlP in acute exposure (6 mg/kg) resulted in an increase in hydroxyl radicals and lipid peroxidation in a time-dependent fashion, suggesting an interaction of delivering electrons of phosphine with mitochondrial respiratory chain and oxidative stress. Iron sucrose, as an electron receiver, can compete with mitochondrial respiratory chain complexes and divert electrons to another pathway. The present findings supported the idea that iron sucrose could normalize the activity of mitochondrial electron transfer chain and cellular ATP level as vital factors for cell escaping from AlP poisoning. © 2015 Informa Healthcare USA, Inc. All rights reserved

Molecular and biochemical evidence on the protection of cardiomyocytes from phosphine-induced oxidative stress, mitochondrial dysfunction and apoptosis by acetyl-l-carnitine

The aim of the present study was to investigate the efficacy of acetyl-l-carnitine (ALCAR) on pathologic changes of mitochondrial respiratory chain activity, ATP production, oxidative stress, and cellular apoptosis/necrosis induced by aluminum phosphide (AlP) poisoning. The study groups included: the Sham that received almond oil only; the AlP that received oral LD50 dose of aluminum; the AC-100, AC-200, and AC-300 which received concurrent oral LD50 dose of AlP and single 100, 200, and 300mg/kg of ALCAR by intraperitoneal injection. After 24h, the rats were sacrificed; the heart and blood sample were taken for measurement of biochemical and mitochondrial factors. The results specified that ALCAR significantly attenuated the oxidative stress (elevated ROS and plasma iron levels) caused by AlP poisoning. ALCAR also increased the activity of cytochrome oxidase, which in turn amplified ATP production. Furthermore, flow cytometric assays and caspase activity indicated that ALCAR prohibited AlP-induced apoptosis in cardiomyocytes. © 2015 Elsevier B.V.

Air Entrainment in Skimming Flow on Stepped Spillways: the Effect of an Abrupt Slope Change

Numerous stepped spillways were built during the last decades. In particular, a stepped spillway may be integrated economically into the downstream face of a RCC gravity dam, or on valley flanks besides embankment or rockfill dams, where slope changes may naturally be implemented due to topography and economic reasons. This paper presents and discusses preliminary results on the air entrainment in the vicinity of an abrupt change chute slope, namely the air concentration distribution and the mean air concentration. A significant influence was observed on the air entrainment pattern, with a decrease of the mean air concentration immediately upstream of the slope change, followed by a marked increase immediately downstream, and a subsequent decrease further down the flatter chute, approaching a practically constant value. Considerable larger air entrainment was observed shortly downstream of the slope change cross-section, in comparison with that found upstream, in the quasi-uniform flow

Investigation of the possible biological activities of a poisonous South African plant ; Hyaenanche globosa (Euphorbiaceae)

The present study was undertaken to explore the possible biochemical activities of Hyaenanche globosa Lamb. and its compounds. Two different extracts (ethanol and dichloromethane) of four different parts (leaves, root, stem, and fruits) of H. globosa were evaluated for their possible antibacterial, antityrosinase, and anticancer (cytotoxicity) properties. Two pure compounds were isolated using column chromatographic techniques. Active extracts and pure compounds were investigated for their antioxidant effect on cultured ‘Hela cells’. Antioxidant/oxidative properties of the ethanolic extract of the fruits of H. globosa and purifi ed compounds were investigated using reactive oxygen species (ROS), ferric-reducing antioxidant power (FRAP), and lipid peroxidation thiobarbituric acid reactive substance (TBARS) assays. The ethanolic extract of the leaves and fruits of H. globosa showed the best activity, exhibiting a minimum inhibitory concentration (MIC) of 3.1 mg/ ml and a minimum bactericidal concentration (MBC) of 1.56 and 6.2 mg/ml, respectively, against M. smegmatis. The ethanolic extract of the fruits of H. globosa (F.E) showed the highest percentage of inhibitory activity of monophenolase (90.4% at 200 g/ml). In addition, F.E exhibited 50% inhibitory concentration (IC50) of 37.7 g/ml on the viability of ‘HeLa cells’ using cytotoxicity MTT assay. Subsequently, F.E was fractionated using phase-partitioning with n-hexane, ethyl acetate, and n-butanol. The cytotoxicity of these fractions were determined in vitro using different cancer cell lines. The n-hexane fraction exhibited the highest activity of toxicity. Therefore, this fraction was subjected to further separation by chromatographic methods. Two pure compounds known as: ‘Tutin’ and ‘hyenanchin’ were isolated and their structures were determined by NMR spectroscopic methods. Unpredictably, none of them showed signifi cant (P 0.01) inhibition on cell viability/proliferation at the concentrations that were used. F.E showed significant anti-tyrosinase, antibacterial, and cytotoxicity effects, therefore it can be considered as an effective inhibitor alone or in combination with other plant extracts.http://www.phcog.com

Growth inhibition and induction of apoptosis in human cancerous HeLa cells by Maytenus procumbens

The possible biochemical activities of the acetonic/ethanolic extract of the leaves of Maytenus procumbens (L.M.P), and its isolated compounds were investigated in the present study. In cytotoxicity assay, L.M.P showed IC50 of 68.79, 51.22, 78.49, 76.59, and 76.64 lg/ml on Caco-2, HeLa, HT29, NIH3T3, and T47D cells, respectively. Bioassay guided fractionation led to the isolation and identification of a new triterpene: ‘30-hydroxy-11a-methoxy-18b-olean-12-en-3-one’ (HMO) in addition to a known terpenoid: ‘asiatic acid’ (AA). HMO exhibited the most cytotoxicity against HeLa cells and was further investigated for its ability to induce apoptosis in HeLa cells. HMO induced apoptosis up to 20.41% in HeLa cells versus control group (0.40%). Antioxidant/oxidative properties of L.M.P and HMO were investigated using extracellular (DPPH), and intracellular (ROS) assays. Experimental samples represented a time and concentrationdependent formation of ROS in Hela cells. Generation of ROS seems one of the mechanisms by which HMO induces apoptosis in Hela cells. Conclusion is that the active components in L.M.P might serve as a mediator of the ROS scavenging system and have the potential to act as prooxidant or antioxidant depending on the biological environment of the cells.Pharmaceutical Sciences Research Center (PSRC) and Tehran University of Medical Sciences (TUMS), Tehran, Iran.http://www.elsevier.com/locate/foodchemtoxhb201

Rapamycin-loaded, capryol� 90 and oleic acid mediated nanoemulsions: Formulation development, characterization and toxicity assessment

This study was planned to explore the capability of nanoemulsions (NEs) consisting of Capryol� 90 and oleic acid for the delivery of rapamycin (RAP). Permeability and cytotoxicity of RAP-loaded NEs were also inspected. Pseudo-ternary phase diagrams were created with oleic acid and Capryol� 90 (as oil phase) and four surfactants and co-surfactants at various weight ratios (Rsm). Selected NEs from O/W region on the phase diagrams with the drug concentration of 1 mg/mL, were prepared via the spontaneous emulsification technique, characterized for particle size and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release was determined for a period of 48 h using a dialysis sac. The assay of RAP was determined using HPLC technique. Cytotoxicity of NEs was evaluated by MTT assay on breast cancer cell line, namely SKBR-3. The permeability of RAP-loaded NEs across Caco-2 monolayers was assessed by measurement of TEER (transepithelial electrical resistance) value. The intracellular uptake of coumarin 6-loaded NEs by SKBR-3 cells was also investigated using florescence microscopy. NEs containing oleic acid/Tween 20/propylene glycol, Capryol� 90/Tween 20/iso-propanol, and Capryol� 90/Cremophor® RH40/Transcutol® P showed more cytotoxicity and permeability compared with the RAP methanolic solution. The minimum toxic concentration of RAP in NE formulations was found to be 7.5 µg/mL. The highest intracellular uptake was observed for the NE composed of Capryol� 90/Tween 20/iso-propanol which was in consistent with the results obtained from cytotoxicity and permeability tests. The overall results implicated that this novel carrier was effective for enhancing RAP permeation in Caco-2 cell membrane along with enhancement of cytotoxicity. © 2018, Iranian Journal of Pharmaceutical Research. All rights reserved

Plant species in Oak (Quercus brantii Lindl.) understory and their relationship with physical and chemical properties of soil in different altitude classes in the Arghvan valley protected area, Iran

The present survey was carried out in Oak (Quercus brantii Lindl.) woodlands of Arghvan valley protected area, in Ilam province, western Iran. The main aim of this study was to survey the understory vegetation of oak in different classes of altitude (1400-1600, 1600-1800 and >1800 m) in the southern aspects, and their relationship with physical and chemical properties of soil. Four transects, with an interval of 200 m were selected from the lowest to the highest points of hillside. 25 individual oak trees were selected on and out of the transects as a plot center. The plot area was obtained using Whittaker’s nested plots and species / area curve. In order to find the relationship between soil properties and vegetation, and also to determine the most effective factors on the distribution of vegetation, multivariate procedures, i.e., Principal Component Analysis (PCA) and Canonical Correspondence Analysis (CCA) were used. Based on these analyses three groups were obtained. These groups exactly coordinated with our sample plots in altitudinal classes and had different soil and vegetation characteristics. The most important factors in the lowland group were pH, SP, OC, N,P and K, and those in the highland group were altitude, BD and stone percentage. The midland group was intermediate to these two groups, although its conditions were more similar to the highland group. The results also indicated a decrease in Shannon-Weiner and Margalef’s indices from lowland toward the highland

Design and characterization of biodegradable multi layered electrospun nanofibers for corneal tissue engineering applications

YesTissue engineering is one of the most promising areas for treatment of various ophthalmic diseases particularly for patients who suffer from limbal stem cell deficiency and this is due to the lack of existence of appropriate matrix for stem cell regeneration. The aim of this research project is to design and fabricate triple layered electrospun nanofibers as a suitable corneal tissue engineering scaffold and the objective is to investigate and perform various in vitro tests to find the most optimum and suitable scaffold for this purpose. Electrospun scaffolds were prepared in three layers. Poly(d, l-lactide-co-glycolide; PLGA, 50:50) nanofibers were electrospun as outer and inner layers of the scaffold and aligned type I collagen nanofibers were electrospun in the middle layer. Furthermore, the scaffolds were cross-linked by 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide hydrochloride and glutaraldehyde. Structural, physical, and mechanical properties of scaffolds were investigated by using N2 adsorption/desorption isotherms, Fourier transform infrared spectroscopy, contact angle measurement, tensile test, degradation, shrinkage analysis, and scanning electron microscopy (SEM). In addition, capability to support cell attachment and viability were characterized by SEM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and 4′,6-diamidino-2-phenylindole staining. According to the result of Brunauer–Emmett–Teller analysis, specific surface area of electrospun scaffold was about 23.7 m2 g-1. Tensile tests on cross-linked scaffolds represented more suitable hydrophilicity and tensile behavior. In addition, degradation rate analysis indicated that noncross-linked scaffolds degraded faster than cross-linked one and cross-linking led to controlled shrinkage in the scaffold. The SEM analysis depicted nano-sized fibers in good shape. Also, the in vitro study represented an improved cell attachment and proliferation in the presence of human endometrial stem cells for both cross-linked and noncross-linked samples. The current study suggests the possibility of producing an appropriate substrate for successful cornea tissue engineering with a novel design.Deputy of Research, Tehran University of Medical Science. Grant Number: 93‐01‐33‐2561

The Antioxidant And Anti-inflammatory Properties Of Chamomile And Its Constituents

Introduction: Chamomile (Matricaria chamomilla L.), as widely used as a medicinal herb and is brewed beverages, and has been used for the treatment of several conditions. The evidence from in vitro, in vivo, and clinical studies suggests that chamomile and its many flavonoid components have anti-oxidant and anti-inflammatory properties. This review aimed to provide an overview of the chemical constituents of chamomile and the effectiveness of the chamomile preparations and several of its constituents for the treatment of several medical conditions. Methods: The present comprehensive review study was conducted by searching electronic databases including Scopus, Web of Sciences, Embase, and PubMed, using relevant keywords. Results: Both animal and human studies indicate the positive effects of chamomile on the antioxidant enzyme activity. However, the mechanisms involved in the action of chamomile against the production of ROS remain still unknown. When it comes to its anti-inflammatory properties, a number of in vitro, in vivo, and clinical investigations have been reported regarding to the selective inhibition of COX-2, suppression of NO production, prevention of IL-1β, IL-6 and TNFα-induced NO levels, reduction of iNOS mRNA and protein expression, impediment of leukocyte adhesion and adhesion protein up-regulation in human endothelial cells, and blockage of IL-1 α-induced prostaglandin production, TNF-α-induced IL-6 and IL-8 release. Conclusions: Current studies suggest that chamomile and its flavonoid components have anti-oxidant and anti-inflammatory properties. On the basis of the existing evidences, chamomile appears to ameliorate several diseases caused by oxidative stress as well as inflammatory reactions