Protective effects of Y-27632 on acute dichlorvos poisoning in rats

Anticholinesterase poisoning is an important health problem in developing countries, and understanding of its underlying mechanisms is essential for the effective treatment. This study is designed to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced cardiac toxicity and mortality in rats. Rats were randomly divided into 4 groups: control (corn oil), dichlorvos (30 mg/kg intraperitoneally), and 1- and 10-mg/kg Y-27632 + dichlorvos groups. After 6 hours of intraperitoneal injection, venous blood and cardiac samples were obtained, biochemical or immunohistochemical analyses were performed, and the intensity of muscle fasciculation was recorded. Serum cholinesterase activities were suppressed with dichlorvos, and these reductions were inhibited with Y-27632 pretreatment. Serum creatine kinase, creatine kinase-MB activities, and myoglobin and N-terminal probrain natriuretic peptide concentrations were not markedly affected with poisoning or Y-27632. Although serum nitric oxide concentrations did not change with dichlorvos, cardiac nitric oxide levels were markedly increased with Y-27632 pretreatment. Cardiac glutathione levels also increased with 1 mg/kg Y-27632. There was no staining for apoptosis, and immunohistochemical analyses of inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Both doses of Y-27632 abolished mortality in rats with acute dichlorvos exposure (100% survival). These results show that administration of Rho-kinase inhibitor can produce protective effects against dichlorvos intoxication in rats. These findings may provide new possibilities for the treatment of organophosphate poisoning. © 2010 Elsevier Inc. All rights reserved

Oral deltamethrin ingestion due in a suicide attempt

Deltamethrin intoxication is uncommon throughout the world. The toxicity of insecticides containing pyrethroids is considered relatively lower than that of other insecticides such as compounds containing orga-nophosphate. Acute deltamethrin poisoning due to oral ingestions is relatively rare. This report describes a case of a 32-year-old woman admitted to the emergency department (ED) with irritability, muscle cramps, discomfort, sensation of burning, loss of sensation in her feet and arms and dyspnea due to deltamethrin ingestion. Deltamethrin intoxication should be considered as a differential diagnosis in patients presented to ED with nonspecific neurological symptoms. The supportive treatment in acute phase of intoxication is critical in the management of these patients since higher doses of deltamethrin ingestion may cause severe symptoms

Cardiac effects of magnesium sulfate pretreatment on acute dichlorvos-induced organophosphate poisoning: An experimental study in rats

Although atropine and oximes are traditionally used in the management of organophosphate poisoning, investigations have been directed to finding additional therapeutic approaches. Thus, the aim of this study was to evaluate the cardiac effects of magnesium sulfate pretreatment on dichlorvos intoxication in rats. Rats were randomly divided into three groups as control, dichlorvos, and magnesium sulfate groups. After 6 h of dichlorvos or corn oil (as a vehicle) injection, venous blood samples were collected, and cardiac tissue samples were obtained. Biochemical analyses were performed to measure some parameters on serum and cardiac tissue. Immunohistochemical analyses of apoptosis and inducible nitric oxide (NO) synthase showed no change in cardiac tissue. Serum cholinesterase levels were markedly depressed with dichlorvos, and further suppressed markedly with magnesium sulfate pretreatment. Although we have demonstrated that serum NO levels in dichlorvos and magnesium sulfate groups were lower than the control group, cardiac tissue NO levels in magnesium sulfate group were higher than the other two groups. Mortality was not significantly affected with magnesium sulfate pretreatment. Uncertainty still persists on the right strategies for the treatment of organophosphate acute poisoning; however, it was concluded that our results do not suggest that magnesium sulfate therapy is beneficial in the management of acute dichlorvos-induced organophosphate poisoning, and also further studies are required. © Springer Science+Business Media, LLC 2009

Formulation of effects of atropine, pralidoxime and magnesium sulfate on cardiac tissue levels of nitric oxide, malondialdehyde and glutathione in organophosphate poisoning using artificial neural network

Anticholinesterase poisoning is an important health problem in our country, and a complete understanding of its underlying mechanisms is essential for the emergency physician. So, this study focused on two purposes. First one was aimed to investigate the biochemical analysis to determine the tissue levels of malondialdehyde (MDA), glutathione and nitric oxide (NO). Secondly, it was planned to model and formulate the effects of some drugs on cardiac tissues levels of NO, MDA and glutathione in acute organophosphate poisoning in rats by the application of neural network based on experimental results. It has been planned to determine whether artificial neural network (ANN) is appropriate tool to analyze and formulate it. As a result, it has been considered that ANN can be effectively used to model NO, MDA and glutathione level. The performances of ANN formulation versus target experimental values are found to be quite high. It is concluded that, proposed NN models are also presented as simple explicit mathematical functions for further use by researchers. Crown Copyright © 2009

Cardiac damage in acute organophosphate poisoning in rats: Effects of atropine and pralidoxime{star, open}

Anticholinesterase poisoning is an important health problem in our country, and a complete understanding of its underlying mechanisms is essential for the emergency physician. Thus, we aimed to investigate the cardiac biochemical parameters and mortality in dichlorvos-induced poisoning in rats. Rats were randomly divided into 5 groups as control (corn oil), dichlorvos, atropine, pralidoxime, and atropine+pralidoxime groups. Immunohistochemical analyses of apoptosis and inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Serum cholinesterase levels were suppressed with dichlorvos, and these reductions were inhibited with atropine and/or pralidoxime pretreatment. Serum levels of creatine kinase, creatine kinase-MB, cardiac troponin I, myoglobin, and N-terminal probrain natriuretic peptide were not affected with poisoning. Malondialdehyde and glutathione levels were not statistically significant between the groups. Although serum nitric oxide levels in the dichlorvos group were lower than those in the control group, cardiac nitric oxide levels in the atropine+pralidoxime group were markedly higher than those in the dichlorvos group. Atropine, pralidoxime, and atropine+pralidoxime pretreatments markedly reduced the mortality. In conclusion, our results implied that measured cardiac markers especially N-terminal probrain natriuretic peptide may not contribute to the early (first 6 hours) diagnosis of cardiotoxicity in dichlorvos-induced poisoning in rats. These results also showed that acute dichlorvos administration did not cause significant cardiac damage, and oxidative stress does not play a marked role in dichlorvos-induced poisoning. Besides, cardiac nitric oxide may produce protective effect on myocardium with atropine+pralidoxime therapy in rats. © 2009 Elsevier Inc. All rights reserved

Effects of atropine and pralidoxime pretreatment on serum and cardiac oxidative stress parameters in acute dichlorvos toxicity in rats

Recent several studies have reported that oxidative stress could be an important component of the mechanism of cardiotoxicity due to organophosphate-induced toxicity. The aim of this study is to evaluate the oxidative and antioxidative parameters in cardiac toxicity of organophosphate poisoning, and determine the effects of atropine and pralidoxime on this parameters. The experimental groups were randomly divided into five groups as control (corn oil), dichlorvos (30 mg/kg), atropine (10 mg/kg), pralidoxime (40 mg/kg), and atropine (10 mg/kg) + pralidoxime (40 mg/kg) groups. Serum cholinesterase levels were suppressed with dichlorvos, and these reductions were inhibited with atropine and/or pralidoxime pretreatment. Serum, but not cardiac, total free sulfhydryl groups and paraoxonase activities were significantly increased in the pralidoxime group when compared to the control group. Serum arylesterase activities were elevated in the dichlorvos, atropine, pralidoxime, and atropine + pralidoxime groups when compared to the control group (P < 0.05). Total oxidant status, oxidative stress index, malondialdehyde and catalase activities in serum and cardiac tissues were not markedly different between the groups. No significant changes were also observed with cardiac myeloperoxidase and serum ceruloplasmin activities. In conclusion, these results showed that acute dichlorvos administration did not cause marked cardiac damage, and oxidative stress probably does not play a major role in dichlorvos-induced poisoning. On the other hand, especially pralidoxime treatment markedly increased the serum total free sulfhydryl groups, paraoxonase and arylesterase activities. However, the underlying mechanisms for these changes are not exactly known. © 2010 Elsevier Inc

Investigation of the Rho-kinase 2 gene Thr431Asn polymorphism in migraine

Background: Migraine has a complex etiology determined by genetic and environmental factors, but the molecular mechanisms and genetics of this disease have not yet been fully clarified. Aim: This case/control study was designed to analyze the genotype distributions and allele frequencies for the Rho-kinase 2 (ROCK2) gene Thr431Asn polymorphism among the migraine patients. Materials and Methods: A total of 155 migraine patients and 155 healthy age and sex matched controls were included in this study. Genomic deoxyribonucleic acid from migraine patients and controls was analyzed by real-time polymerase chain reaction. Results: Neither genotype distributions nor the allele frequencies for the Thr431Asn polymorphism showed a significant difference between the groups. In addition, there were no marked differences in genotype and allele frequencies for the migraine without aura and migraine with aura subgroups when compared with control group. Conclusion: This is the first study to show that the ROCK2 gene Thr431Asn polymorphism is not a risk factor for the migraine in the Turkish population

Association of TRPM Channel Gene Polymorphisms with Systemic Sclerosis

WOS: 000365993400016PubMed ID: 26546534Background/Aim: Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc. Materials and Methods: A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system. Results: There were marked increases in the CC genotype (94.7% vs 81.8%, p<0.0001) and C allele frequencies (97.0% vs. 90.1%, p<0.0001) in the TRPM3 rs1328142, and TT genotype (19.0% vs. 7.8%, p=0.0002) in TRPM5 rs34551253 (Ala456Thr) polymorphism in SSc patients when compared to controls. TRPM3 gene rs1328142 polymorphism was also markedly associated with disease phenotype. However, no associations with the other 23 polymorphisms studied were found. Conclusion: This is the first study to examine the involvement of TRPM channel gene variations on the risk of SSc incidence. Our results suggest roles of TRPM3 and TRPM5 gene variants in the susceptibility to or clinical expression of SSc in the Turkish population