BACKGROUND： Organophosphorus insecticides may promote the accumulation of acetylcholine at synapses and the neuromuscular junction by inhibiting acetylcholinesterase activity to cause disturbance of neural signal con...BACKGROUND： Organophosphorus insecticides may promote the accumulation of acetylcholine at synapses and the neuromuscular junction by inhibiting acetylcholinesterase activity to cause disturbance of neural signal conduction and induce a toxic reaction. Organophosphorus insecticides may act on M2 muscarinic acetylcholine receptors, whose combination with G proteins is regulated by phosphorylation of G protein-coupled receptor kinase 2. OBJECTIVE： To investigate the effects of organophosphorus insecticides on the phosphorylation of G protein-coupled receptor kinase 2-mediated M2 muscarinic acetylcholine receptors and to reveal other possible actions of organophosphorus insecticides. DESIGN, TIME AND SETTING： An observational study, which was performed in the Central Laboratory of Shenyang Medical College, and Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University from June 2002 to December 2004. MATERIALS： Paraoxon, parathion, chlorpyrifos, and chlorpyrifos oxon were provided by Chem Service Company, USA, [γ -p^32] ATP and [^35S]GTP γ S by New England Nuclear Life Science Products, and recombinant β 2-adrenergic receptor membrane protein by Sigma Company, USA. METHODS： The M2 muscarinic acetylcholine receptor was extracted and purified from pig brain using affinity chromatography. Subsequently, the purified M2 muscarinic acetylcholine receptor, G protein-coupled receptor kinase 2, and [γ -p^32] ATP were incubated with different concentrations of paraoxon and chlorpyrifos oxon together. The mixture then underwent polyacrylamide gel electrophoresis, and the gel film was dried and radioactively autographed to detect phosphorylation of the M2 muscarinic acetylcholine receptor. Finally, the radio-labeled phosphorylated M2 receptor protein band was excised for counting with an isotope liquid scintillation counter. MAIN OUTCOME MEASURES： Effects of chlorpyrifos oxon, paraoxon, chlorpyrifos, and parathion in different concentrations on the phosphorylation of the M2 muscarinic acetylcholine receptor; effects of chlorpyrifos oxon on the phosphorylation of the β -adrenergic receptor. RESULTS： Chlorpyrifos oxon could completely inhibit the phosphorylation of the M2 muscarinic acetylcholine receptor, and its IC50 was 70 μ mol/L. Chlorpyrifos could also inhibit the phosphorylation of the M2 muscarinic acetylcholine receptor. However, paraoxon and parathion could not inhibit the phosphorylation of the M2 muscarinic acetylcholine receptor. Chlorpyrifos oxon in different concentrations could also not inhibit the phosphorylation of the β 2-adrenergic receptor catalyzed by G protein-coupled receptor kinase 2. CONCLUSION： Different kinds of organophosphorus insecticides have different effects on the phosphorylation of the G protein-coupled receptor kinase 2-mediated M2 muscarinic acetylcholine receptor. Organophosphorus insecticides possibly have different toxic effects.展开更多
Considering that the involvement of reactive oxygen species （ROS） has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E （100 mg/kg body wei...Considering that the involvement of reactive oxygen species （ROS） has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E （100 mg/kg body weight） on mice （25 -30 mg） treated with diazinon （32.5 or 16.25 mg/kg body weight） organophosphate insecticide for 14 days. Subehronic DZN exposure and the protective effects of vitamins E （vitE） were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase （ ALT）, aspartate aminotaransferase （ AST）, alkaline phosphatise （ ALP）, and some parameters of kidney function （urea and creatinine） in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon （DZNH） decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significandy. Moreover, there was a statistically significant decrease in haemoglobin （Hb）, red blood cell （RBC） and hematocrit （Hct） in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE ＋ DZNtreated groups. According to the present study, we conclude that vitE ean reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function [ Current Zoology 55 （3） ： 219 - 226, 2009].展开更多
文摘BACKGROUND： Organophosphorus insecticides may promote the accumulation of acetylcholine at synapses and the neuromuscular junction by inhibiting acetylcholinesterase activity to cause disturbance of neural signal conduction and induce a toxic reaction. Organophosphorus insecticides may act on M2 muscarinic acetylcholine receptors, whose combination with G proteins is regulated by phosphorylation of G protein-coupled receptor kinase 2. OBJECTIVE： To investigate the effects of organophosphorus insecticides on the phosphorylation of G protein-coupled receptor kinase 2-mediated M2 muscarinic acetylcholine receptors and to reveal other possible actions of organophosphorus insecticides. DESIGN, TIME AND SETTING： An observational study, which was performed in the Central Laboratory of Shenyang Medical College, and Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University from June 2002 to December 2004. MATERIALS： Paraoxon, parathion, chlorpyrifos, and chlorpyrifos oxon were provided by Chem Service Company, USA, [γ -p^32] ATP and [^35S]GTP γ S by New England Nuclear Life Science Products, and recombinant β 2-adrenergic receptor membrane protein by Sigma Company, USA. METHODS： The M2 muscarinic acetylcholine receptor was extracted and purified from pig brain using affinity chromatography. Subsequently, the purified M2 muscarinic acetylcholine receptor, G protein-coupled receptor kinase 2, and [γ -p^32] ATP were incubated with different concentrations of paraoxon and chlorpyrifos oxon together. The mixture then underwent polyacrylamide gel electrophoresis, and the gel film was dried and radioactively autographed to detect phosphorylation of the M2 muscarinic acetylcholine receptor. Finally, the radio-labeled phosphorylated M2 receptor protein band was excised for counting with an isotope liquid scintillation counter. MAIN OUTCOME MEASURES： Effects of chlorpyrifos oxon, paraoxon, chlorpyrifos, and parathion in different concentrations on the phosphorylation of the M2 muscarinic acetylcholine receptor; effects of chlorpyrifos oxon on the phosphorylation of the β -adrenergic receptor. RESULTS： Chlorpyrifos oxon could completely inhibit the phosphorylation of the M2 muscarinic acetylcholine receptor, and its IC50 was 70 μ mol/L. Chlorpyrifos could also inhibit the phosphorylation of the M2 muscarinic acetylcholine receptor. However, paraoxon and parathion could not inhibit the phosphorylation of the M2 muscarinic acetylcholine receptor. Chlorpyrifos oxon in different concentrations could also not inhibit the phosphorylation of the β 2-adrenergic receptor catalyzed by G protein-coupled receptor kinase 2. CONCLUSION： Different kinds of organophosphorus insecticides have different effects on the phosphorylation of the G protein-coupled receptor kinase 2-mediated M2 muscarinic acetylcholine receptor. Organophosphorus insecticides possibly have different toxic effects.
基金the grant No1-429-199 which supported by projects department of Taif University,KSA.
文摘Considering that the involvement of reactive oxygen species （ROS） has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E （100 mg/kg body weight） on mice （25 -30 mg） treated with diazinon （32.5 or 16.25 mg/kg body weight） organophosphate insecticide for 14 days. Subehronic DZN exposure and the protective effects of vitamins E （vitE） were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase （ ALT）, aspartate aminotaransferase （ AST）, alkaline phosphatise （ ALP）, and some parameters of kidney function （urea and creatinine） in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon （DZNH） decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significandy. Moreover, there was a statistically significant decrease in haemoglobin （Hb）, red blood cell （RBC） and hematocrit （Hct） in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE ＋ DZNtreated groups. According to the present study, we conclude that vitE ean reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function [ Current Zoology 55 （3） ： 219 - 226, 2009].
