Microtransplantation of rat brain neurolemma into the plasma membrane of Xenopus laevis oocytes is an ex vivo method used to study channels and receptors in their native state using standard electrophysiological appro...Microtransplantation of rat brain neurolemma into the plasma membrane of Xenopus laevis oocytes is an ex vivo method used to study channels and receptors in their native state using standard electrophysiological approaches.In this review,we show that oocytes injected with adult rat brain neurolemma elicited tetrodotoxin-sensitive inward ion currents upon membrane depolarization,which were increased in a concentration-dependent manner by treatment with the pyrethroid insecticides permethrin and deltamethrin.Under our initial protocols,oocyte health was reduced over time and neurolemma incorporation varied between batches of oocytes from different frogs,limiting the usefulness of the assay for regulatory issues.A collection of changes to the assay procedure,data acceptance criteria,and analysis method yield substantially improved precision and,hence,assay performance.These changes established this ex vivo approach as a toxicologically relevant assay to study the toxicodynamic action of pyrethroids on ion channels in their native state using neurolemma fragments prepared from juvenile and adult rat brains.展开更多
The study of the interaction of three glycol ethers, i.e. 2-methoxyethanol (ME), 2-ethoxyethanol (EE) and 2-butoxyethanol (BE) administered subcutaneously for 4 weeks and ethanol simultaneously given as 10% w/v soluti...The study of the interaction of three glycol ethers, i.e. 2-methoxyethanol (ME), 2-ethoxyethanol (EE) and 2-butoxyethanol (BE) administered subcutaneously for 4 weeks and ethanol simultaneously given as 10% w/v solution for drinking in male rats, was carried out from a toxicodynamic point of view. Administered alone, ME (2.5 and 5.0 mM/kg), EE (2.5 and 5.0 mM/kg) or BE (0.75 and 1.25 mM/kg) resulted in a decrease of red blood cells (RBC), packed cell volumes (PCV), and hemoglobin concentration (HGB), as well as an increase in mean corpuscular volume (MCV) and reticulocyte count (Ret). In the rats co-ex- posed to ethanol and EGAEs, a significantly less pronounced hematological changes in comparison with animal exposed to these ethers alone were seen. The rats simultaneously exposed to ethanol and both ME and EE at the lower dose demonstrated mainly protection from the alterations in leukocyte system. In contrast, in the rats which consumed ethanol and were simultaneously treated with the higher dose of ME or EE (5.0 mM/kg) the amelioration of same hematological parameters were displayed. The intake of ethanol along with BE treatment at both doses resulted in markedly ameliorated hematological parameters, compared to those which were changed by BE alone. In conclusion, the decrease of the hemolytic effects of EGAEs is ethanol dependent. Ethanol is a substrate of alcohol dehydrogenase (ADH), and affinity of this enzyme to ethanol is greater than that to glycol ethers. It is possible that ethanol results in the change in EGAEs metabolism.展开更多
基金supported by the Council of the Advancement of Pyrethroid Human Risk Assessment(CAPHRA)(#S17110000000004).
文摘Microtransplantation of rat brain neurolemma into the plasma membrane of Xenopus laevis oocytes is an ex vivo method used to study channels and receptors in their native state using standard electrophysiological approaches.In this review,we show that oocytes injected with adult rat brain neurolemma elicited tetrodotoxin-sensitive inward ion currents upon membrane depolarization,which were increased in a concentration-dependent manner by treatment with the pyrethroid insecticides permethrin and deltamethrin.Under our initial protocols,oocyte health was reduced over time and neurolemma incorporation varied between batches of oocytes from different frogs,limiting the usefulness of the assay for regulatory issues.A collection of changes to the assay procedure,data acceptance criteria,and analysis method yield substantially improved precision and,hence,assay performance.These changes established this ex vivo approach as a toxicologically relevant assay to study the toxicodynamic action of pyrethroids on ion channels in their native state using neurolemma fragments prepared from juvenile and adult rat brains.
文摘The study of the interaction of three glycol ethers, i.e. 2-methoxyethanol (ME), 2-ethoxyethanol (EE) and 2-butoxyethanol (BE) administered subcutaneously for 4 weeks and ethanol simultaneously given as 10% w/v solution for drinking in male rats, was carried out from a toxicodynamic point of view. Administered alone, ME (2.5 and 5.0 mM/kg), EE (2.5 and 5.0 mM/kg) or BE (0.75 and 1.25 mM/kg) resulted in a decrease of red blood cells (RBC), packed cell volumes (PCV), and hemoglobin concentration (HGB), as well as an increase in mean corpuscular volume (MCV) and reticulocyte count (Ret). In the rats co-ex- posed to ethanol and EGAEs, a significantly less pronounced hematological changes in comparison with animal exposed to these ethers alone were seen. The rats simultaneously exposed to ethanol and both ME and EE at the lower dose demonstrated mainly protection from the alterations in leukocyte system. In contrast, in the rats which consumed ethanol and were simultaneously treated with the higher dose of ME or EE (5.0 mM/kg) the amelioration of same hematological parameters were displayed. The intake of ethanol along with BE treatment at both doses resulted in markedly ameliorated hematological parameters, compared to those which were changed by BE alone. In conclusion, the decrease of the hemolytic effects of EGAEs is ethanol dependent. Ethanol is a substrate of alcohol dehydrogenase (ADH), and affinity of this enzyme to ethanol is greater than that to glycol ethers. It is possible that ethanol results in the change in EGAEs metabolism.
