Publications by authors named "Hossein Rastegar"

44 Publications

Quinazolinone-dihydropyrano[3,2-b]pyran hybrids as new α-glucosidase inhibitors: Design, synthesis, enzymatic inhibition, docking study and prediction of pharmacokinetic.

Bioorg Chem 2021 Apr 8;109:104703. Epub 2021 Feb 8.

Nano Alvand Company, Avicenna Tech Park, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A series of new quinazolinone-dihydropyrano[3,2-b]pyran derivatives 10A-L were synthesized by simple chemical reactions and were investigated for inhibitory activities against α-glucosidase and α-amylase. New synthesized compounds showed high α-glucosidase inhibition effects in comparison to the standard drug acarbose and were inactive against α-amylase. Among them, the most potent compound was compound 10L (IC value = 40.1 ± 0.6 µM) with inhibitory activity around 18.75-fold more than acarboase (IC value = 750.0 ± 12.5 µM). This compound was a competitive inhibitor into α-glucosidase. Our obtained experimental results were confirmed by docking studies. Furthermore, the cytotoxicity of the most potent compounds 10L, 10G, and 10N against normal fibroblast cells and in silico druglikeness, ADME, and toxicity prediction of these compounds were also evaluated.
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http://dx.doi.org/10.1016/j.bioorg.2021.104703DOI Listing
April 2021

Design, synthesis, characterization, enzymatic inhibition evaluations, and docking study of novel quinazolinone derivatives.

Int J Biol Macromol 2021 Feb 19;170:1-12. Epub 2020 Dec 19.

Department of Chemistry, Faculty of Sciences, Ataturk University, 25240, Erzurum, Turkey.

In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with K values in the range of 19.28-135.88 nM for α-glycosidase (K value for standard inhibitor = 187.71 nM), 0.68-23.01 nM for acetylcholinesterase (K value for standard inhibitor = 53.31 nM), 1.01-29.56 nM for butyrylcholinesterase (K value for standard inhibitor = 58.16 nM), 10.25-126.05 nM for human carbonic anhydrase I (K value for standard inhibitor = 248.18 nM), and 13.46-178.35 nM for human carbonic anhydrase II (K value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.121DOI Listing
February 2021

Survey of protein-based sport supplements for illegally added anabolic steroids methyltestosterone and 4-androstenedione by UPLC-MS/MS.

Steroids 2021 Jan 5;165:108758. Epub 2020 Nov 5.

Food and Drug Laboratories Research Center (FDLRC), Food and Drug Organization (FDO), Ministry of Health (MOH), Iran; Food and Drug Control Laboratories References Center (FDLCRC), Food and Drug Organization (FDO), Ministry of Health (MOH), Iran. Electronic address:

There is some evidence that marketable supplements contain hormones not declared on the product label. The presence of these androgenic anabolic steroids (AAS) in sports supplements can be considered an adulteration and affect the health of consumers, who are predominantly athletes. This study aimed to measure anabolic hormones (methyltestosterone and 4-androstenedione) in sport supplements. Ultra Performance Liquid chromatography coupled mass spectrometry (UPLC-MS/MS) with electrospray ionization (ESI) in positive mode was employed under the Multiple Reaction Monitoring (MRM) ion program. To overcome matrix effects and quantify the selected analyte, the calibration curve was made using Matrix Match method. The LOQ and LOD were 1 ng/g and 0.3 ng/g for both analytes. The recovery of 4-androstenedione and methyltestosterone was in the range of 86.87-107.35 and 77.31-113.98, respectively. In terms of reproducibility, CV % for 4-androstenedione and methyltestosterone ranged from 6.56 to 16.87% and 1.45-15.12%, respectively. 4-androstenedione was found in 11 samples including 9 whey as 1.578 ± 0.154 ng/g and 2 whey albumin samples with an amount of 1.134 ng/g and 1.474 ng/g. Consequently, continuous controlling of sport supplements comprising intentionally or unintentionally added androgens could be important for health and discuss in the context of compliance with anti-doping.
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http://dx.doi.org/10.1016/j.steroids.2020.108758DOI Listing
January 2021

An Overview on Probiotics as an Alternative Strategy for Prevention and Treatment of Human Diseases.

Iran J Pharm Res 2019 ;18(Suppl1):31-50

Department of Medicine and epidemiology, School of veterinary Medicine, University of California, Davis, USA.

Probiotics are viable and useful microorganisms, which are beneficial factors for human and animal health by altering their microbial flora. Most of the probiotics belong to a large group of bacteria in the human gastrointestinal tract. There are several clinical shreds of evidence that show anti-carcinogenic effects of probiotics through altering digestive enzymes, inhibition of carcinogenic agents, and modulating the immune responses in experimental animals. Many studies have been performed to evaluate the potential effectiveness of probiotics in treating or preventing neurological diseases such as MS and novel treatment modality for T1D. The purpose of this study is to have an overview on probiotic microorganisms and to review the previous researches on the effects of probiotics on health through currently available literatures. The study was performed using following keywords; Probiotics, Cancer, Immune system, Multiple Sclerosis (MS) and Diabetes mellitus. PubMed/Medline, Clinicaltrials.gov, Ovid, Google Scholar, and Reaxcys databases used to find the full text of related articles. According to the current available data on probiotics and related health-promoting benefits, it seems that, consumption of probiotics can lead to the prevention and reduction the risk of cancer, diabetes, and multiple sclerosis. Although for the better and more decisive conclusion, there is a need to larger sample size clinical studies with more focus on the safety of these biological agents and their possible beneficial effects on different population.
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http://dx.doi.org/10.22037/ijpr.2020.112232.13620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393061PMC
January 2019

Comparison of UVA Protection Factor Measurement Protocols.

Clin Cosmet Investig Dermatol 2020 8;13:351-358. Epub 2020 May 8.

Iranian Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran.

Background: In the past, it was taught that UVA wavelengths (320- 400nm) only plays a major role in skin aging but recently the scientific researches also show that UVA cause cancerous keratinocyte cells in deep layer of the epidermis. Therefore, the protective ability of the product against UVA is important in addition to protection against UVB rays. The UVA protective factor (UVA-PF) is used to evaluate the effectiveness of sunscreen products against UVA rays. This study aims to review and compare all outstanding protocols in the field of UVA-PF measurement and finally the introduction of the best method of measuring UVA-PF based on the further benefits.

Materials And Methods: Four standards including ISO 24443 (AS/NZS 2604: 2012 recommended approach), CEN 2006, FDA 2007 and FDA 2011 are selected.

Results: In order to measure UVA-PF with in vivo method, two standards of CEN 2006 and FDA 2007 recommended persistent pigment darkening (PPD) method. Although the general principle of both is similar, there are some differences in detail. For in vitro measurement of UVA-PF, CEN and FDA 2011 standards use critical wavelengths. FDA 2007 introduces the modified Diffey fraction, and ISO 24443 standard meets the UVA-PF measurement in a manner that is consistent with PPD.

Conclusion: Finally, this review discussed the comparison of all in vitro and in vivo UVA-PF measurement standards and provided information in the form of texts and tables to move towards the creation of an integrated standard. Since in vitro methods of UVA-PF measurement are not reproducible due to differences in test conditions, it may be concluded that the in vivo PPD method is a more suitable option.
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http://dx.doi.org/10.2147/CCID.S244898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244352PMC
May 2020

Design and synthesis of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids as new anti-diabetic agents: in vitro α-glucosidase inhibition, kinetic and docking studies.

Mol Divers 2020 Mar 18. Epub 2020 Mar 18.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Fourteen novel 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a-n were synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1H-imidazole and various benzyl azides. The synthesized compounds 8a-n were evaluated against yeast α-glucosidase, and all these compounds exhibited excellent inhibitory activity (IC values in the range of 85.6 ± 0.4-231.4 ± 1.0 μM), even much more potent than standard drug acarbose (IC = 750.0 μM). Among them, 4,5-diphenyl-imidazol-1,2,3-triazoles possessing 2-chloro and 2-bromo-benzyl moieties (compounds 8g and 8i) demonstrated the most potent inhibitory activities toward α-glucosidase. The kinetic study of the compound 8g revealed that this compound inhibited α-glucosidase in a competitive mode. Furthermore, docking calculations of these compounds were performed to predict the interaction mode of the synthesized compounds in the active site of α-glucosidase. A novel series of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a-n was synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1Himidazole and various benzyl azides. The synthesized compounds 8a-n were evaluated against yeast α-glucosidase and all these compounds exhibited excellent inhibitory activity (IC50 values in the range of 85.6 ± 0.4-231.4 ± 1.0 μM), even much more potent than standard drug acarbose (IC50 = 750.0 μM).
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http://dx.doi.org/10.1007/s11030-020-10072-8DOI Listing
March 2020

Lovastatin alters neurotrophin expression in rat hippocampus‑derived neural stem cells in vitro.

Acta Neurobiol Exp (Wars) 2019 ;79(4):413-420

Food and Drug Research Institute, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran.

Neural stem/progenitor cells hold valuable potential for the treatment of neurodegenerative disorders. The modulation of intrinsic growth factor expression, such as neurotrophins and their receptors, is a necessary step in achieving neural stem cells (NSCs) therapy. The statins have recently been reported to provide both anti‑inflammatory and neuroprotective effects. In the developing and mature nervous systems, neurotrophic factors are known to impact neuronal growth and survival. In this study, we investigated for a positive effect of lovastatin on the expression of neurotrophins in the neonatal rat hippocampus‑derived NSCs. NSCs were isolated and cultured up to passage three. To confirm cellular identity, immunocytochemical evaluation and flow cytometry analysis were performed using specific antibodies. To determine the optimum concentration of lovastatin, the MTT assay was used. Neurotrophin expression was evaluated using quantitative real‑time reverse transcription‑polymerase chain reaction (RT‑qPCR). Flow cytometry results demonstrated that NSCs were positive for nestin, a marker for neural progenitor cells. An increase in cellular viability was observed with a 24 h exposure of lovastatin. Moreover, results showed an increase in mRNA expression for all neurotrophins compared to the control group. Taken together, the results of this study add to the growing body of literature on the neuroprotective effects of statins in neurological disorders. Lovastatin is a promising therapeutic agent for the treatment of neurodegenerative disorders.
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June 2020

Design and Synthesis of Novel Cytotoxic Indole-Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study.

Chem Biodivers 2019 Apr 3;16(4):e1800470. Epub 2019 Apr 3.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, 1417653761, Tehran, Iran.

In this work, two novel series of indole-thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF-7, A-549, and Hep-G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A-549 and Hep-G2 than MCF-7. Among them, (2E)-2-{[2-(4-chlorophenyl)-1H-indol-3-yl]methylidene}-N-(4-methoxyphenyl)hydrazinecarbothioamide (8l) was found to be the most potent compound against A-549 and Hep-G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A-549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.
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http://dx.doi.org/10.1002/cbdv.201800470DOI Listing
April 2019

Design and synthesis of new imidazo[1,2-b]pyrazole derivatives, in vitro α-glucosidase inhibition, kinetic and docking studies.

Mol Divers 2020 Feb 2;24(1):69-80. Epub 2019 Mar 2.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

A new series of imidazo[1,2-b]pyrazole derivatives 4a-o was designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. All compounds showed high inhibitory activity in the range of IC = 95.0 ± 0.5-372.8 ± 1.0 µM as compared to standard drug acarbose (IC = 750 ± 1.5 µM) and were also found to be non-cytotoxic. Among the synthesized compounds, the most potent compound was compound 4j with eightfold higher inhibitory activity compared to acarbose. Like acarbose, compound 4j inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most potent compounds 4j, 4f, 4o, and 4c were also conducted.
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http://dx.doi.org/10.1007/s11030-019-09925-8DOI Listing
February 2020

Design and synthesis of novel quinazolinone-1,2,3-triazole hybrids as new anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and docking study.

Bioorg Chem 2019 03 11;83:161-169. Epub 2018 Oct 11.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity leading to efficient anti-diabetic agents. All synthesized compounds exhibited good inhibitory activity against yeast α-glucosidase (IC values in the range of 181.0-474.5 µM) even much more potent than standard drug acarbose (IC = 750.0). Among them, quinazolinone-1,2,3-triazoles possessing 4-bromobenzyl moiety connected to 1,2,3-triazole ring (10g and 10p) demonstrated the most potent inhibitory activity towards α-glucosidase. Compound 10g inhibited α-glucosidase in a competitive manner with K value of 117 µM. Furthermore, the binding modes of the most potent compounds 10g and 10p in the α-glucosidase active site was studied through in silico docking studies. Also, lack of cytotoxicity of compounds 10g and 10p was confirmed via MTT assay.
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http://dx.doi.org/10.1016/j.bioorg.2018.10.023DOI Listing
March 2019

Porous MnFeO@SiO magnetic glycopolymer: A multivalent nanostructure for efficient removal of bacteria from aqueous solution.

Ecotoxicol Environ Saf 2018 Dec 28;166:277-284. Epub 2018 Sep 28.

Cosmetic Products Research Center, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran.

The focuses of this research is to prepare an efficient magnetic glycopolymer for bacteria removal from aqueous solution. To perform this idea; porous MnFeO@SiO was functionalized with glucose and or maltose as an anchors to adhere onto bacteria cell surface. Aminopropyltriethoxysilane was employed to link the saccharides on magnetic nanoparticle surface. The hybrid materials were characterized with XRD, VSM, FT-IR, FESEM, TEM, zeta potential measurement and elemental mapping. Microscopic image showed that MnFeO is in cluster form composed from tiny nanoparticles. After saccharide functionalization hybrid composite generate hyper-crosslinked porous structure as a result of polysilicate formation due to hydrolysis of silica source. Escherichia coli and bacillus subtilis were selected as sample pathogens to evaluate the bacteria capturing ability of the magnetic glycopolymer. At the optimum conditions (pH = 6, time of 20 min, dosage of 15 mg) removal efficiency was more than 99% using both saccharide.
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http://dx.doi.org/10.1016/j.ecoenv.2018.09.086DOI Listing
December 2018

The concentration and probabilistic health risk assessment of pesticide residues in commercially available olive oils in Iran.

Food Chem Toxicol 2018 Oct 3;120:32-40. Epub 2018 Jul 3.

Department of Food Science, Faculty of Food Engineering, University of Campinas, Campinas, SP, Brazil. Electronic address:

This study was undertaken to analyze 29 pesticides residues in 37 commercially olive oil collected samples from Iran's markets using Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) approach along with acetonitrile for the extraction, surface adsorbents for clean-up procedure, following with a gas chromatography-mass spectroscopy (GC-MS). In order to eliminate the matrix effect, the calibration curves were drawn using spiked samples with the Area under curve (AUC) portion calculation of pesticide residue to AUC internal standard (Triphenyl Methane (TPM)). Moreover, the probabilistic health risk assessment includes non-carcinogenic and carcinogenic risk were estimated by target hazard quotient (THQ), total target hazard quotient (TTHQ) and cancer risk (CR) using the Monte Carlo Simulation (MCS) method. The calibration curves were linear in the range of 10-1500 ng/g, and R was higher than 0.994. All pesticides recoveries as average were in the range of 77.97-112.65%. The respective numbers attributed to LOD and LOQ were 3-5 ng/g and 8-15 ng/g. Results showed that 29.7% of samples were contaminated by pesticides which according to Iranian regulation, while in 7 cases banned pesticides were detected. Only 4 samples are noncompliant with EU regulation. The rank order of pesticides based on THQ was Heptachlor > DDT > Pretilachlor. Also, TTHQ for adults was 0.139; and children 0.467. The rank order of pesticides based on CR was Heptachlor > DDT. Consumers (adults and children) are not at non-carcinogenic risk due to ingestion of oil olive content (THQ and TTHQ < 1 value) but are at considerable carcinogenic (CR > 1E-6). According to the observed profile of pesticide in olive oil samples, which are mostly banned according to Iranian regulation, further improvements in agriculture procedures of cultivated olive in Iran, as well as required assessments of imported olive oil, was recommended.
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http://dx.doi.org/10.1016/j.fct.2018.07.002DOI Listing
October 2018

Exposure Assessment for Some Pesticides through Rice Consumption in Iran Using a Multiresidue Analysis by GC-MS.

Iran J Pharm Res 2018 ;17(1):124-139

Food and Drug Laboratories Research Center, Ministry of Health and Medical Education, Tehran, Iran.

In communities which consume rice as main food, importance of risk assessment for contaminants is always taken into consideration by health authorities. The present study is an attempt for monitoring of 56 pesticides from different chemical groups in rice samples collected from local markets in Tehran and estimation of daily intake of interested pesticides through this monitoring. A valid method based on spiked calibration curves and QuEChERS sample preparation was developed for determination of pesticides residue in rice by GC/MS. The analytical results of the proposed method were in good agreement with the proficiency test (FAPAS 0969). One-hundred-thirty-five rice samples were analyzed and 11 pesticide residues were found in 10.4% of the samples. Of which 5.2% were contaminated with unregulated pesticides. None of the samples, which were contaminated with regulated pesticides, had contamination higher than maximum residue limit. The mean estimated dose (ED) was calculated with respect of mean of contamination and mean daily consumption of rice. ED of the found pesticides is much lower than the related ADIs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937084PMC
January 2018

The effect of nano-silver packaging in increasing the shelf life of nuts: An model.

Ital J Food Saf 2017 Oct 7;6(4):6874. Epub 2017 Nov 7.

Health Research Center, Baqiyatallah University of Medical Sciences, Tehran.

Nano packaging is currently one of the most important topics in food packaging technologies. The aim of the application of this technology in food packaging is increasing shelf life of foods by preventing internal and external corruption and microbial contaminations. Use of silver nanoparticles in food packaging has recently attracted much attention. The aim of this study was to investigate the effect of nano-silver packaging in increasing the shelf life packages of nuts in an model. In this experimental study, the effects of different nano-silver concentrations (0, 1, 2 and 3 percent) on biological and chemical properties of 432 samples of nuts including walnuts, hazelnuts, almonds and pistachios were evaluated during 0, 3, 6, 9, 12, 15, 18, 21 and 24 months. In most samples, different concentrations of nano-silver (1, 2 and 3 %) significantly reduced total microbial count, mold and coliform counts compared to control group and the 3% nano-silver concentration was more effective than other concentrations (P<0.05). Moreover, using this packaging yielded an antioxidant effect especially when 2% and 3% nano-silver concentrations were used. Nano-silver also prevented growth of mold and so prevented aflatoxin production in all treatment groups. Results of chemical and biological tests showed that the silver nanoparticles had a significant effect on increasing the shelf life of nuts. The highest shelf life belonged to pistachios, almonds, hazelnuts and walnuts with 20, 19, 18 and 18 months, respectively. The shelf life was associated with amount of silver nanoparticles. The highest antimicrobial activity was observed when 3% nano-silver concentration was used in pistachios. The shelf life of control groups in similar storage conditions were calculated for an average of 13 months. In conclusion, the results of this study demonstrate the efficacy of nano-silver packing in increasing shelf life of nuts. Hence, use of nano-silver packaging in food industry, especially in food packaging is recommended.
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http://dx.doi.org/10.4081/ijfs.2017.6874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850069PMC
October 2017

Glucose reinforced FeO@cellulose mediated amino acid: Reusable magnetic glyconanoparticles with enhanced bacteria capture efficiency.

Carbohydr Polym 2017 Aug 26;170:190-197. Epub 2017 Apr 26.

Cosmetic Products Research Center, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran.

In this study glucose reinforced FeO@cellulose glyconanoparticles (MGN) were prepared using epichlorohydrin and amino acid (lysine and arginine) as a linker. Bacillus capturing capability of amino acid modified FeO@cellulose was compared to the glucose reinforced system. Results showed enhanced bacterial capturing of MGN relative to amino acid modified particles. Bacterial capturing efficiencies were increased to 91% and 95% in the magnetic cellulose arginine-glucose (MCAG) and magnetic cellulose lysine-glucose (MCLG), respectively, which confirmed the role of synergism on microbial efficiency. Effective parameters on bacterial capturing efficiency including; solution pH, contact time, dosage of MGN and the presence of some anions were also investigated. Moreover, presented system was employed for bacteria capturing from river water, sea water and milk samples. The results showed that these nanocomposites have good performance to be used as reusable antimicrobial magnetic materials. The results showed that these nanocomposites have good reusability after three cycles of sorption and desorption which confirmed the efficiency of the system for bacterial removing from water solutions.
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http://dx.doi.org/10.1016/j.carbpol.2017.04.078DOI Listing
August 2017

Molecularly Imprinted Polymer of Colocynthin, An Effective Tool for Quality Control of Citrullus colocynthis Extracts.

Curr Drug Discov Technol 2017 ;14(3):169-180

Food and Drug Control Laboratories and Research Center, MOH and ME, P.O. Box 11136-15911, Tehran. Iran.

Background: Different parts of Colocynth, Citrullus colocynthis (L.) Schrad., are used in traditional phytotherapy and homeopathy.

Objective: In our new approach, a molecularly imprinted polymer was synthesized to absorb colocynthin, the major plant marker, and its capability was evaluated using HPLC-UV.

Method: A new method was considered to achieve optimal conditions. FT-infrared, N2 adsorption porosimetry, fluorescent and scanning electron microscopy and thermo gravimetric profile of the polymers were studied. The imprinted polymer was applied as molecularly imprinted solid phase extraction sorbent to enrich colocynthin from colocynth oil extract, a traditional medicine dosage form.

Results: The imprinted polymer showed high capacity and affinity toward colocynthin. Physical assessments demonstrated no major differences between imprinted and nonimprinted polymers. The imprinted polymer was able to absorb colocynthin more efficiently than non-imprinted and control simple solvent extraction from the real sample.

Conclusion: In conclusion, this polymer is capable of being applied as a promising adsorbent for analysis of colocynth traditional medicine products.
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http://dx.doi.org/10.2174/1570163814666170104152226DOI Listing
June 2018

Attenuated Lead Induced Apoptosis in Rat Hepatocytes in the Presence of Lycopersicon Esculentum.

Acta Med Iran 2016 Apr;54(4):240-4

Cosmetic Products Research Center, Iran Food and Drug Adminstration, Ministry of Health and Medical Education, Tehran, Iran. AND Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.

Lead (Pb), has, for decades, being known for its adverse effects on various body organs and systems. In the present study, the damage of Pb on the Liver tissue apoptosis was investigated, and Lycopersicon esculentum as an antioxidants source was administered orally to prevent the adverse effects of Pb. Eighteen Wistar rats, randomized into three groups (n=6), were used for this study. Animals in Group A served as the control and were drinking distilled water. Animals in Groups B and C were drinking 1%Lead acetate (LA). Group C animals were, in addition to drinking LA, treated with 1.5 ml/day of Lycopersicon esculentum. Treatments were for three months. The obtained results showed that lead acetate caused significant reductions in the liver weight, plasma and tissue superoxide dismutase and catalase activity, but a significant increase in plasma and tissue malondialdehyde concentration but Lycopersicon esculentum have an inhibitory effect on LA liver adverse effect. So, it can be concluded that Lycopersicon esculentum have a significant protective effect on liver lead acetate adverse effects as well as, lead acetate-induced oxidative stress.
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April 2016

Study of Silymarin and Vitamin E Protective Effects on Silver Nanoparticle Toxicity on Mice Liver Primary Cell Culture.

Acta Med Iran 2016 Feb;54(2):85-95

Department of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran. AND Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran. AND Cosmetic Products Research Center, Iran Food and Drug Adminstration, Ministry of Health and Medical Education, Tehran, Iran.

Nanotechnology is a most promising field for generating new applications in medicine, although, only few nano products are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nano-silver has biological properties which are significant for consumer products, food technology, textiles, and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products. The use of nano-silver is becoming more and more widespread in medicine and related applications, and due to its increasing exposure, toxicological and environmental issues need to be raised. Cytotoxicity induced by silver nanoparticles (AgNPs) and the role that oxidative stress plays in this process were demonstrated in human hepatoma cells AgNPs agglomerated in the cytoplasm and nuclei of treated cells, and they induced intracellular oxidative stress. AgNP reduced ATP content of the cell and caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. Silymarin was known as a hepatoprotective agent that is used in the treatment of hepatic diseases including viral hepatitis, alcoholic liver diseases, Amanita mushroom poisoning, liver cirrhosis, toxic and drug-induced liver diseases. It promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation, and protects against glutathione depletion. Vitamin E is a well-known antioxidant and has hepatoprotective effect in liver diseases. In this study, we investigated the cytotoxic effects of Ag NPs on primary liver cells of mice. Cell viability (cytotoxicity) was examined with MTT assay after primary liver cells of mice exposure to AgNPs at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration- dependent decrease of cell viability (IC50 value = 121.7 ppm or µg/ml). Then the hepatoprotective effect of silymarin and vitamin E were experimented on silver nanoparticle toxicity on mice liver primary cell culture. The results showed that silymarin at 600 µg/ml and vitamin E at 2500 µmol/l have protective effects on silver nanoparticle toxicity on mice liver primary cell culture. Viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles at 121.7 ppm and co-treatment of silymarin, and vitamin E is more than viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles and silymarin or silver nanoparticles and vitamin E.
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February 2016

Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation.

Adv Pharm Bull 2015 Nov 30;5(4):497-505. Epub 2015 Nov 30.

Food and Drug Research Center, Food and Drug Organization, MOH&ME, Tehran, Iran.

Purpose: Aggregation suppressing additives have been used to stabilize proteins during manufacturing and storage. Interferonβ-1b is prone to aggregation because of being non-glycosylated. Aggregation behavior of albumin-free formulations of recombinant IFNβ-1b was explored using additives such as n-dodecyl-β-D-maltoside, Tween 20, arginine, glycine, trehalose and sucrose at different pH.

Methods: Fractional factorial design was applied to select major factors affecting aggregation in solutions. Box-Behnken technique was used to optimize the best concentration of additives and protein.

Results: Quadratic model was the best fitted model for particle size, OD350 and OD280/OD260. The optimal conditions of 0.2% n-Dodecyl-β-D-maltoside, 70 mM arginine, 189 mM trehalose and protein concentration of 0.50 mg/ml at pH 4 were achieved. A potency value of 91% ± 5% was obtained for the optimized formulation.

Conclusion: This study shows that the combination of n-Dodecyl-β-D-maltoside, arginine and trehalose would demonstrate a significant stabilizing and anti-aggregating effect on the liquid formulation of interferonβ-1b. It can not only reduce the manufacturing costs but will also ease patient compliance.
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http://dx.doi.org/10.15171/apb.2015.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729353PMC
November 2015

Preparation of Immunotoxin Herceptin-Botulinum and Killing Effects on Two Breast Cancer Cell Lines.

Asian Pac J Cancer Prev 2015 ;16(14):5977-81

Iran Food and Drug Administration, Tehran, Iran E-mail :

Background: Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin, a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2- neu receptors, but it is an expensive drug with only 20% beneficial rate of survival. This study introduces a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study.

Materials And Methods: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) according to the supplier's guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader.

Results: Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group.

Conclusions: Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor.
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http://dx.doi.org/10.7314/apjcp.2015.16.14.5977DOI Listing
June 2016

Halal authenticity of gelatin using species-specific PCR.

Food Chem 2015 Oct 21;184:203-6. Epub 2015 Mar 21.

Food & Drug Control Reference Laboratories Center, Food and Drug Organization, Ministry of Health and Medical Education, Tehran, Iran.

Consumption of food products derived from porcine sources is strictly prohibited in Islam. Gelatin, mostly derived from bovine and porcine sources, has many applications in the food and pharmaceutical industries. To ensure that food products comply with halal regulations, development of valid and reliable analytical methods is very much required. In this study, a species-specific polymerase chain reaction (PCR) assay using conserved regions of mitochondrial DNA (cytochrome b gene) was performed to evaluate the halal authenticity of gelatin. After isolation of DNA from gelatin powders with known origin, conventional PCR using species-specific primers was carried out on the extracted DNA. The amplified expected PCR products of 212 and 271 bp were observed for porcine and bovine gelatin, respectively. The sensitivity of the method was tested on binary gelatin mixtures containing 0.1%, 1%, 10%, and 100% (w/w) of porcine gelatin within bovine gelatin and vice versa. Although most of the DNA is degraded due to the severe processing steps of gelatin production, the minimum level of 0.1% w/w of both porcine and bovine gelatin was detected. Moreover, eight food products labeled as containing bovine gelatin and eight capsule shells were subjected to PCR examination. The results showed that all samples contained bovine gelatin, and the absence of porcine gelatin was verified. This method of species authenticity is very useful to verify whether gelatin and gelatin-containing food products are derived from halal ingredients.
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http://dx.doi.org/10.1016/j.foodchem.2015.02.140DOI Listing
October 2015

Water-compatible molecularly imprinted polymer as a sorbent for the selective extraction and purification of adefovir from human serum and urine.

J Sep Sci 2015 May 6;38(10):1755-62. Epub 2015 May 6.

Water Safety Research Center, Food and Drug Laboratory Research Center, Food and Drug Control Laboratories, MOH ME, Tehran, Iran.

A molecularly imprinted polymer has been synthesized to specifically extract adefovir, an antiviral drug, from serum and urine by dispersive solid-phase extraction before high-performance liquid chromatography with UV analysis. The imprinted polymers were prepared by bulk polymerization by a noncovalent imprinting method that involved the use of adefovir (template molecule) and functional monomer (methacrylic acid) complex prior to polymerization, ethylene glycol dimethacrylate as cross-linker, and chloroform as porogen. Molecular recognition properties, binding capacity, and selectivity of the molecularly imprinted polymers were evaluated and the results show that the obtained polymers have high specific retention and enrichment for adefovir in aqueous medium. The new imprinted polymer was utilized as a molecular sorbent for the separation of adefovir from human serum and urine. The serum and urine extraction of adefovir by the molecularly imprinted polymer followed by high-performance liquid chromatography showed a linear calibration curve in the range of 20-100 μg/L with excellent precisions (2.5 and 2.8% for 50 μg/L), respectively. The limit of detection and limit of quantization were determined in serum (7.62 and 15.1 μg/L), and urine (5.45 and 16 μg/L). The recoveries for serum and urine samples were found to be 88.2-93.5 and 84.3-90.2%, respectively.
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http://dx.doi.org/10.1002/jssc.201401492DOI Listing
May 2015

Molecularly imprinted nanoparticles prepared by miniemulsion polymerization as a sorbent for selective extraction and purification of efavirenz from human serum and urine.

J Chromatogr B Analyt Technol Biomed Life Sci 2015 Jan 22;974:1-8. Epub 2014 Oct 22.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A molecularly imprinted polymer (MIP) has been synthesized in order to specifically extract efavirenz from serum and urine by dispersive solid-phase extraction following by HPLC-UV analysis. The imprinted nanoparticles were prepared by miniemulsion polymerization method using efavirenz as template molecule and methacrylic acid as functional monomer. Molecular recognition properties, binding capacity and selectivity of the MIPs were evaluated and the results revealed that the obtained MIPs had high specific retention for efavirenz in aqueous medium. The MIP was used as a molecular sorbent for the separation of efavirenz from human serum and urine. The extraction of efavirenz by MIP coupled with HPLC analysis showed a linear calibration curve in the range of 50-300 μg/L with exellent precisions (3.66% and 4.6% for 100 and 300 μg/L respectively). The limit of detection (LOD) and limit of quantification (LOQ) were determind in serum (17.3 and 57.5 μg/L) and urine (10.6 and 36.2 μg/L). The maximum recoveries for serum and urine samples were found to be 95.2% and 92.7% respectively. Due to the high precision and accuracy, this method may be the UV-HPLC choice with MIP extraction for bioequivalence analysis of efavirenz in serum and urine.
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http://dx.doi.org/10.1016/j.jchromb.2014.10.012DOI Listing
January 2015

A spectroscopic investigation of the interaction between c-MYC DNA and tetrapyridinoporphyrazinatozinc(II).

J Biol Phys 2014 Jun 15;40(3):275-83. Epub 2014 May 15.

Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 45195-1159, Iran,

The c-MYC gene plays an important role in the regulation of cell proliferation and growth and it is overexpressed in a wide variety of human cancers. Around 90% of c-MYC transcription is controlled by the nuclease-hypersensitive element III1 (NHE III1), whose 27-nt purine-rich strand has the ability to form a G-quadruplex structure under physiological conditions. Therefore, c-MYC DNA is an attractive target for drug design, especially for cancer chemotherapy. Here, the interaction of water-soluble tetrapyridinoporphyrazinatozinc(II) with 27-nt G-rich strand (G/c-MYC), its equimolar mixture with the complementary sequence (GC/c-MYC) and related C-rich oligonucleotide (C/c-MYC) is investigated. Circular dichroism (CD) measurements of the G-rich 27-mer oligonucleotide in 150 mM KCl, pH 7 demonstrate a spectral signature consistent with parallel G-quadruplex DNA. Furthermore, the CD spectrum of the GC rich oligonucleotide shows characteristics of both duplex and quadruplex structures. Absorption spectroscopy implies that the complex binding of G/c-MYC and GC/c-MYC is a two-step process; in the first step, a very small red shift and hypochromicity and in the second step, a large red shift and hyperchromicity are observed in the Q band. Emission spectra of zinc porphyrazine are quenched upon addition of three types of DNA. According to the results of spectroscopy, it can be concluded the dominant binding mode is probably, outside binding and end stacking.
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http://dx.doi.org/10.1007/s10867-014-9348-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059838PMC
June 2014

Evaluation of heavy metals contamination in Iranian foodstuffs: canned tomato paste and tomato sauce (ketchup).

Food Addit Contam Part B Surveill 2014 21;7(1):74-8. Epub 2013 Nov 21.

a Heavy Metals Analysis Laboratory , Food and Drug Laboratory Research Center, Food and Drug Organization , Tehran , Iran.

One hundred and thirty-five samples of canned tomato paste and 30 tomato sauces (ketchup) samples (23 and 10 brands, respectively) purchased from wholesale markets in the Tehran, Iran, during the period 2010-2013 were analysed. Levels of lead and cadmium were determined by graphite furnace atomic absorption spectrophotometer (GF-AAS) and arsenic by hydride vapour generation (HG-AAS or VGA). Average concentration of arsenic found in the tomato paste and ketchup samples was 62 ± 14 and 48 ± 12 ng g(-1), respectively. Cadmium values in 7% of tomato paste and 10% of ketchup samples were below the limit of quantification (LOQ). Lead concentrations were below LOQ in 75% of tomato paste and 77% of ketchup samples. Values obtained for these heavy metals in all samples were lower than the limits of national and international standards.
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http://dx.doi.org/10.1080/19393210.2013.848384DOI Listing
December 2014

Toxicity Effect of Silver Nanoparticles on Mice Liver Primary Cell Culture and HepG2 Cell Line.

Iran J Pharm Res 2014 ;13(1):235-42

Department of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Nano-silver (AgNP) has biological properties which are significant for consumer products, food technology, textiles and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles are largely used in various commercially available products. Thus, the use of nano-silver is becoming more and more widespread in medicine. In this study we investigated the cytotoxic effects of AgNPs on liver primary cells of mice, as well as the human liver HepG2 cell. Cell viability was examined with MTT assay after HepG2 cells exposure to AgNPs at 1, 2, 3, 4, 5, 7.5, 10 ppm compared to mice primary liver cells at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration-dependent decrease of cell viability in both cells. IC50 value of 2.764 ppm (µg/mL) was calculated in HepG2 cell line and IC50 value of 121.7 ppm (µg/mL) was calculated in primary liver cells of mice. The results of this experiment indicated that silver nanoparticles had cytotoxic effects on HepG2 cell line and primary liver cells of mice. The results illustrated that nano-silver had 44 times stronger inhibitory effect on the growth of cancerous cells (HepG2 cell line) compared to the normal cells (primary liver cells of mice). which might further justify AgNPs as a cytotoxic agents and a potential anticancer candidate which needs further studies in this regard.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985257PMC
April 2014

Detection of genetically modified maize in processed foods sold commercially in iran by qualitative PCR.

Iran J Pharm Res 2013 ;12(1):25-30

Food and Drug Laboratory Research Center, Food and Drug Organization, Ministry of Health and Medical Education, Tehran, Iran. ; Department of Molecular Biology, Food and Drug Control Reference Laboratory, Ministry of Health and Medical Education, Tehran, Iran.

Detection of genetically modified organisms (GMOs) in food is an important issue for all the subjects involved in food control and customer's right. Due to the increasing number of GMOs imported to Iran during the past few years, it has become necessary to screen the products in order to determine the identity of the consumed daily foodstuffs. In this study, following the extraction of genomic DNA from processed foods sold commercially in Iran, qualitative PCR was performed to detect genetically modified maize. The recombinant DNA target sequences were detected with primers highly specific for each investigated transgene such as CaMV35s gene, Bt-11, MON810 and Bt-176 separately. Based on the gel electrophoresis results, Bt- 11 and MON810 events were detected in some maize samples, while, in none of them Bt- 176 modified gene was detected. For the first time, the results demonstrate the presence of genetically modified maize in Iranian food products, reinforcing the need for the development of labeling system and valid quantitative methods in routine analyses.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813200PMC
November 2013

The metabolic function of hepatocytes differentiated from human mesenchymal stem cells is inversely related to cellular glutathione levels.

Cell Biochem Funct 2014 Mar 5;32(2):194-200. Epub 2013 Sep 5.

Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Differentiation of mesenchymal stem cells (MSCs) to hepatocytes-like cells is associated with alteration in the level of reactive oxygen species (ROS) and antioxidant defense system. Here, we report the role of glutathione in the functions of hepatocytes derived from MSCs. The stem cells undergoing differentiation were treated with glutathione modifiers [buthionine sulfoxide (BSO) or N-acetyl cysteine (NAC)], and hepatocytes were collected on day 14 of differentiation and analysed for their biological and metabolic functions. Differentiation process has been performed in presence of glutathione modifiers viz. BSO and NAC. Depending on the level of cellular glutathione, the proliferation rate of MSCs was affected. Glutathione depletion by BSO resulted in increased levels of albumin and ROS in hepatocytes. Whereas, albumin and ROS were inhibited in cells treated with glutathione precursor (NAC). The metabolic function of hepatocytes was elevated in BSO-treated cells as judged by increased urea, transferrin, albumin, alanine transaminase and aspartate transaminase secretions in the media. However, the metabolic activity of the hepatocytes was inhibited when glutathione was increased by NAC. We conclude that the efficiency of metabolic function of hepatocytes is inversely related to the levels of cellular glutathione. These data may suggest a novel role of glutathione in regulation of metabolic function of hepatocytes.
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http://dx.doi.org/10.1002/cbf.2994DOI Listing
March 2014

An applicable strategy for improvement recovery in simultaneous analysis of 20 pesticides residue in tea.

J Food Sci 2013 May 27;78(5):T792-6. Epub 2013 Mar 27.

Food and Drug Laboratory Research Center and Food and Drug Reference Control Laboratories Center, Food and Drug Organization, MOH & ME, Tehran, Iran.

It is important to have a reliable method to analyze pesticides in tea, a beverage commonly consumed in Iran. A validated method was developed for the determination of 20 pesticides in tea based on QuEChERS sample preparation and capillary gas chromatography-quadrupole mass spectrometry in selective ion monitoring mode (GC-MS/SIM) using triphenyl methane (TPM) solution as an internal standard. We used fortified, extracted, and cleaned-up tea samples instead of calibration standards for quantitation, which substantially reduced adverse matrix-related effects and negative recovery affected by graphite carbon black (GCB) on pesticide analysis. The recovery of pesticides at 3 concentration (40, 60, and 240 ng/g) ranged from 79.5% to 111.4% (n = 3). The method had acceptable repeatability with RSDr < 20%. The limits of quantification (LOQ) for all pesticides were ≤20 ng/g. The analytical results of the proposed method were in good agreement with proficiency test results (FAPAS, 19116). The recoveries and repeatabilities were in accordance with the criteria set by SANCO Guideline. The validated method was suitable for the analysis of pesticides in tea.
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http://dx.doi.org/10.1111/1750-3841.12100DOI Listing
May 2013

Monitoring of some pesticides residue in consumed tea in Tehran market.

Iranian J Environ Health Sci Eng 2013 Jan 12;10(1). Epub 2013 Jan 12.

Food and Drug Laboratory Research Center, Food and Drug Organization, MOH & ME, Tehran, Iran.

Tea is an agricultural product of the leaves, leaf buds, and internodes of various cultivars and sub-varieties of the Camellia sinensis plant, processed and vulcanized using various methods. Tea is a main beverage in Iranian food basket so should be free from toxic elements such as pesticides residue. There is no data bank on the residue of pesticides in the consumed black tea in Iran. The present study is the first attempt for monitoring of 25 pesticide residues from different chemical groups in tea samples obtained from local markets in Tehran, I.R. Iran during the period 2011. A reliable and accurate method based on spiked calibration curve and QuEChERS sample preparation was developed for determination of pesticide residues in tea by gas chromatography-mass spectrometry (GC/MS). The using of spiked calibration standards for constructing the calibration curve substantially reduced adverse matrix-related effects and negative recovery affected by GCB on pesticides. The recovery of pesticides at 3 concentration levels (n = 3) was in range of 81.4 - 99.4%. The method was proved to be repeatable with RSDr lower than 20%. The limits of quantification for all pesticides were ≤20 ng/g. 53 samples from 17 imported and manufactured brand were analyzed. Detectable pesticides residues were found in 28.3% (15 samples) of the samples. All of the positive samples were contaminated with unregulated pesticides (Endosulfan Sulfate or Bifenthrin) which are established by ISIRI. None of the samples had contamination higher than maximum residue limit set by EU and India.
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http://dx.doi.org/10.1186/1735-2746-10-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577662PMC
January 2013