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Sharifi A.M.,Tehran University of Medical Sciences | Sharifi A.M.,Shariati Hospital | Mousavi S.H.,Tehran University of Medical Sciences | Mousavi S.H.,Medical Toxicology Research Center | Jorjani M.,Shahid Beheshti University of Medical Sciences
Cellular and Molecular Neurobiology | Year: 2010

Despite reduction in environmental lead, chronic lead exposure still possess a public health hazard, particularly in children, with devastating effects on developing CNS. To investigate the mechanism of this neurotoxicity, young and adult rats were used to study whether exposure to 500 ppm concentrations of lead could induce apoptosis in hippocampus. 2-4 and 12-14-week-old rats received lead acetate in concentration of 500 ppm for 40 days. Control animals received deionized distilled water. In lead-treated groups, the blood lead levels were increased by 3-4 folds. Light and electron microscopical study of hippocampus revealed increased apoptotic cells. Western blot analysis of Bax and Bcl-2 (pro-and antiapoptotic gene products, respectively) indicated higher expression of Bax protein and no significant change in bcl-2 expression and accordingly increased the Bax/Bcl-2 ratio compared to control group, confirming the histological study. In conclusion, these data suggest that neurotoxicity of chronic lead exposure in hippocampus in vivo may partly be due to facilitation of apoptosis. © Springer Science+Business Media, LLC 2010.


Rezaee R.,Medical Toxicology Research Center | Hassanzadeh-Khayyat M.,Pharmaceutical Research Center | Mehri F.,Medical Toxicology Research Center | Khashyarmanesh Z.,Pharmaceutical Research Center | And 2 more authors.
Drug and Chemical Toxicology | Year: 2012

Water is a necessity for life. Currently, because of different contaminations in tap water, most people prefer using bottled mineral waters. Pesticides (e.g., organophophorous, carbamates, etc.) are among the most dangerous chemicals that may be found in drinking waters, which can cause long- and short-term complications. Because all people consume at least 2L of water per day, water-quality monitoring is vital. In this study, we determined the concentration of three pesticides (aldicarb, parathion, and thiobencarb) in 13 tap-water samples collected from 13 different urban areas and 10 samples of bottled mineral water in Mashhad, a major city in northeast Iran. Samples were analyzed by gas chromatography coupled with a pulsed flame photometric detector after solid-phase extraction. Results showed that 2 of 13 tap-water samples and 2 of 10 bottled mineral water trademarks were contaminated either by parathion or by thiobencarb or both, with concentrations ranging between 0.6 and 0.8 ppb. According to the defined guideline values, determined concentrations of pesticides are below the permissible World Health Organization level for these toxic agents, and it is considered that drinking these tap waters and bottled mineral waters are safe for human consumption. © 2012 Informa Healthcare USA, Inc.


Karimi G.,Medical Toxicology Research Center | Tabrizian K.,Medical Toxicology Research Center | Rezaee R.,Medical Toxicology Research Center
JAMS Journal of Acupuncture and Meridian Studies | Year: 2010

The symptoms of neuropathic pain are often intractable because they are poorly relieved by conventional analgesics. This therapeutic area remains one of the least satisfactorily managed by current drugs. Effective therapy for this type of pain is lacking, and the underlying mechanisms are poorly understood. The present study was undertaken to determine the effect of sciatic nerve ligation on inducing neuropathic pain and to understand the mechanisms involved, and the effect of, an L-nitro-arginine methyl ester (L-NAME)/dextromethorphan combination therapy on reducing neuropathic pain. According to our results, L-NAME and dextromethorphan showed analgesic properties, but only 100 mg/kg L-NAME had an additive effect on the analgesic effects of dextromethorphan. Our observations support the idea that N-methyl-D-aspartate/nitric oxide pathways play an important role in the development of such sciatic nerve ligated-evoked pathological pain conditions, thus this combination therapy could be used instead of conventional treatment. © 2010 Korean Pharmacopuncture Institute.


Mohajeri S.A.,Mashhad University of Medical Sciences | Karimi G.,Medical Toxicology Research Center | Khansari M.R.,Mashhad University of Medical Sciences
Analytica Chimica Acta | Year: 2010

A variety of molecularly imprinted polymers (MIPs) against clozapine (CLZ) were synthesized and their recognition properties were compared with blank non-imprinted polymers. Methacrylic acid (MAA) was used as a functional monomer and Chloroform or tetrahydrofuran (THF) were applied as polymerization solvents. Chloroform as the solvent and MAA/CLZ ratio of 5 was selected as optimized polymerization condition. In Scatchard analysis of MIP-CLZ interactions, two classes of binding sites were found in MIP-high affinity (KD = 14.5 μM) and low affinity (KD = 322.5 μM) binding sites. The polymer was evaluated as a selective sorbent in molecularly imprinted solid-phase extraction (MISPE) of CLZ from human serum. The MISPE procedure was developed and optimized with a recovery of 88-102%. The intra- and inter-day precision values were less than 1.36% and 2.5%, respectively. The selectivity of MISPE for CLZ was studied in comparison with some drugs. These drugs could be present with CLZ, simultaneously in serum of patients. The data indicated that the imprinted polymer had a good selectivity and affinity for CLZ and could be used for selective extraction and analysis of CLZ in human serum. © 2010 Elsevier B.V.


Maleki M.,Mashhad University of Medical Sciences | Karimi G.,Medical Toxicology Research Center | Tafaghodi M.,Mashhad University of Medical Sciences | Raftari S.,Mashhad University of Medical Sciences | Nahidi Y.,Mashhad University of Medical Sciences
Indian Journal of Dermatology | Year: 2012

Cutaneous leishmaniasis is an endemic disease in developing countries caused by different species of leishmania parasite, and if left untreated, it will result in a deformed scar after a relatively long period. Although various systemic and topical treatments have been proposed for leishmaniasis, pentavalent Antimony compounds remain the first-line treatment for it. Considering the cases with treatment failure, potential side effects and reluctance of patients to receive the drug, there are continuing efforts to find better treatment alternatives. Aim: Comparison of the effect of intralesional 2% zinc sulfate injection with Glucantime in treatment of acute cutaneous leishmaniasis. Materials and Methods: In this clinical trial, 45 patients with clinical diagnosis of cutaneous leishmaniasis and positive direct smear for leishman body were treated by intralesional injection of either 2% zinc sulfate or Glucantime. After simple randomization, in one group the patients were treated with 2 bouts of intralesional 2% zinc sulfate with a 2-week interval, and in the other group they were treated with 6 weekly bouts of intralesional Glucantime. The patients were monitored in two week intervals for 8 weeks. Healing of the lesions was evaluated clinically and by direct smear, and the data were analyzed using SPSS (11.5) software, t-Student, Mann-Whitney and Analysis of covariance (ANCOVA) statistical tests. Findings: In the end of study, 34 patients completed the study, 10 of whom received intralesional Glucantime and 24 of whom received intralesional 2% zinc sulfate. The healing rate after 8 weeks was 80% in the group receiving intralesional Glucantime and 33.3% in the one receiving 2% zinc sulfate (P=0.009). Conclusion: Based on the results of this study, intralesional injection of 2% zinc sulfate was less effective in treatment of cutaneous leishmaniasis than intralesional Glucantime.


Riahi B.,Medical Toxicology Research Center | Rafatpanah H.,Mashhad University of Medical Sciences | Mahmoudi M.,Mashhad University of Medical Sciences | Memar B.,Mashhad University of Medical Sciences | And 3 more authors.
Food and Chemical Toxicology | Year: 2010

The immunotoxic effect of paraquat (PQ), a herbicide that has been used widely in agriculture was investigated using Balb/c mice. Paraquat was administered at doses of 1, 0.1, and 0.01. mg/kg for 21. days. Body weight, organ weight, cellularity of spleen, delayed type of hypersensitivity (DTH) response, plaque-forming cell (PFC) assay, hemagglutination titer (HA), quantitative hemolysis of SRBC (QHS) assay, spleen cell subtypes, cytokine production and lymphocyte proliferation assay were studied in various groups of animals. Results showed that high dose of PQ (1. mg/kg) could suppress both cellular and humoral activity of the immune system. PQ at medium dose (0.1. mg/kg) did not show any changes in organ weight, body weight and spleen cellularity but significantly decreased the proliferation response to PHA and the production of IFNγ. PQ at low dose (0.01. mg/kg) did not produce any significant changes in humoral or cellular responses of the immune system. In conclusion, paraquat at high dose has an inhibitory effect on the cell-mediated and humoral immunity. It seems that PQ has no adverse effects on mice immune system at low doses of 0.01. mg/kg, which is two times the PQ allowed daily intake (ADI) limit. © 2010 Elsevier Ltd.


PubMed | Medical Toxicology Research Center
Type: Journal Article | Journal: Journal of immunotoxicology | Year: 2011

The toxic effect of paraquat (PQ), an herbicide that has been used widely in agriculture, on some parameters of the immune system was investigated. PQ was administered to Balb/c mice as intraperitoneal doses of 0.01, 0.1, or 1.0 mg PQ/kg body weight (BW) for a total of 28 days. Besides the histopathological examination of each host?s vital organs, measures of their splenic and bone marrow cellularity, blood macrophage/granulocyte phagocytic activity, total serum immunoglobulin M (IgM) and IgG, complement C3, and splenic CD49b (natural killer) cell levels, as well as of serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase and complement-mediated lytic activity (CH), activities, were then performed following the respective final treatments. The results indicate that high and medium doses of PQ (i.e., 1 and 0.1 mg/kg) could lead to suppressed phagocytic activity by circulating macrophages/granulocytes. The data also revealed that the high PQ dose induced a significant decrease (p<0.05) in spleen cellularity and splenic CD49b cell levels, along with numerous histopathological changes in the spleen. However, at none of the doses tested did PQ produce changes in serum levels of C3, total IgG or IgM, or in the CH. At 0.01 mg PQ/kg/day, no histopathological or functional disturbances were detected. These results indicate that PQ at doses more than 0.1?mg/kg has toxic effects on the cellular components of the innate immune system of Balb/c mice. The present results, however, indicate that at an exposure level below the recommended acceptable daily intake limit of 0.005 mg/kg, no observable immunotoxicity effect might be expected.


PubMed | Medical Toxicology Research Center
Type: Journal Article | Journal: Drug and chemical toxicology | Year: 2012

Water is a necessity for life. Currently, because of different contaminations in tap water, most people prefer using bottled mineral waters. Pesticides (e.g., organophophorous, carbamates, etc.) are among the most dangerous chemicals that may be found in drinking waters, which can cause long- and short-term complications. Because all people consume at least 2L of water per day, water-quality monitoring is vital. In this study, we determined the concentration of three pesticides (aldicarb, parathion, and thiobencarb) in 13 tap-water samples collected from 13 different urban areas and 10 samples of bottled mineral water in Mashhad, a major city in northeast Iran. Samples were analyzed by gas chromatography coupled with a pulsed flame photometric detector after solid-phase extraction. Results showed that 2 of 13 tap-water samples and 2 of 10 bottled mineral water trademarks were contaminated either by parathion or by thiobencarb or both, with concentrations ranging between 0.6 and 0.8 ppb. According to the defined guideline values, determined concentrations of pesticides are below the permissible World Health Organization level for these toxic agents, and it is considered that drinking these tap waters and bottled mineral waters are safe for human consumption.


PubMed | Medical Toxicology Research Center
Type: Journal Article | Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association | Year: 2010

The immunotoxic effect of paraquat (PQ), a herbicide that has been used widely in agriculture was investigated using Balb/c mice. Paraquat was administered at doses of 1, 0.1, and 0.01 mg/kg for 21 days. Body weight, organ weight, cellularity of spleen, delayed type of hypersensitivity (DTH) response, plaque-forming cell (PFC) assay, hemagglutination titer (HA), quantitative hemolysis of SRBC (QHS) assay, spleen cell subtypes, cytokine production and lymphocyte proliferation assay were studied in various groups of animals. Results showed that high dose of PQ (1mg/kg) could suppress both cellular and humoral activity of the immune system. PQ at medium dose (0.1 mg/kg) did not show any changes in organ weight, body weight and spleen cellularity but significantly decreased the proliferation response to PHA and the production of IFNgamma. PQ at low dose (0.01 mg/kg) did not produce any significant changes in humoral or cellular responses of the immune system. In conclusion, paraquat at high dose has an inhibitory effect on the cell-mediated and humoral immunity. It seems that PQ has no adverse effects on mice immune system at low doses of 0.01 mg/kg, which is two times the PQ allowed daily intake (ADI) limit.


PubMed | Medical Toxicology Research Center
Type: Journal Article | Journal: Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences | Year: 2013

More than 100,000 Iranian veterans and civilians still suffer from various long-term complications due to their exposure to sulfur mustard (SM) during the Iran-Iraq war in 1983-88. The aim of the study was to investigate DNA damage of SM in veterans who were exposed to SM, 23-27 years prior to this study.Blood samples were obtained from the veterans and healthy volunteers as negative controls. Lymphocytes were isolated from blood samples and DNA breaks were measured using single-cell microgel electrophoresis technique under alkaline conditions (comet assay). Single cells were analyzed with Tri Tek Comet Score version 1.5 software and DNA break was measured based on the percentage of tail DNA alone, or in the presence of H2O2 (25 M) as a positive control.A total of 25 SM exposed male veterans and 25 male healthy volunteers with similar ages (44.66 6.2 and 42.12 5.75 years, respectively) were studied. Percentage of the lymphocyte DNA damage was significantly (P < 0.01) higher in the SM-exposed individuals than in the controls (6.47 0.52 and 1.31 0.35, respectively). Percentages of DNA damage in the different age groups of 35-39, 40-44, 45-49, and 50-54 years in SM-exposed veterans (5.48 0.17, 6.7 3 1.58, 6.42 0.22, and 7.27 0.38, respectively) were all significantly (P < 0.05) higher than the controls (1.18 0.25, 1.53 0.22, 1.27 0.20, and 1.42 0.10, respectively). The lymphocytes incubated with H2O2 had much higher DNA damage as expected. The average of tail DNA is 42.12 2.75% for control cells + H2O2 and 18.48 2.14% for patients cells + H2O2; P < 0.001.SM exposure of the veterans revealed DNA damage as judged by the comet assay.

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