DEHP(di(2-ethylhexyl) phthalate) is an endocrine disruptor commonly found in plastic products that has been associated with reproduction alterations, but the effect of DEHP on toxicity is still widely unknown. Using D...DEHP(di(2-ethylhexyl) phthalate) is an endocrine disruptor commonly found in plastic products that has been associated with reproduction alterations, but the effect of DEHP on toxicity is still widely unknown. Using DEHP concentrations of 10, 1, and 0.1 mg/L, we showed that DEHP reduced the reproductive capacity of Caenorhabditis elegans after 72 hr. of exposure. DEHP exposure reduced the reproductive capacity in terms of decreased brood sizes, egg hatchability(0.1, 1 and 10 mg/L), and egg-laying rate(1 and 10 mg/L), and increased numbers of fertilized eggs in the uterus(1 and 10 mg/L). DEHP also caused damage to gonad development. DEHP decreased the total number of germline cells, and decreased the relative area of the gonad arm of all exposure groups, with worms in the 1 mg/L DEHP exposure group having the minimum gonad arm area. Additionally, DEHP caused a significant concentration-dependent increase in the expression of unc-86. Autophagy and ROS contributed to the enhancement of DEHP toxicity in reducing reproductive capacity, and glutathione peroxidase and superoxide dismutase were activated as the antioxidant defense in this study. Hence, we found that DEHP has a dual effect on nematodes. Higher concentration(10 mg/L) DEHP can inhibit the expression of autophagy genes( atg-18, atg-7, bec-1, lgg-1 and unc-51), and lower concentrations(0.1 and 1 mg/L) can promote the expression of autophagy genes. Our data highlight the potential environmental risk of DEHP in inducing reproductive toxicity toward the gonad development and reproductive capacity of environmental organisms.展开更多
We previously demonstrated that administering 2-（2-benzofuranyl）-2-imidazolin（2-BFI）, an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immed...We previously demonstrated that administering 2-（2-benzofuranyl）-2-imidazolin（2-BFI）, an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by Wenzhou Medical University in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI（3 mg/kg） through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa＇s method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy. The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling（TUNEL） assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following： Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.展开更多
基金supported by the Fundamental Research Fund of Central Public Welfare Research Institutions in 2019(Innovation team project of new approach and application on substitution toxicology of environmental hormone substances).
文摘DEHP(di(2-ethylhexyl) phthalate) is an endocrine disruptor commonly found in plastic products that has been associated with reproduction alterations, but the effect of DEHP on toxicity is still widely unknown. Using DEHP concentrations of 10, 1, and 0.1 mg/L, we showed that DEHP reduced the reproductive capacity of Caenorhabditis elegans after 72 hr. of exposure. DEHP exposure reduced the reproductive capacity in terms of decreased brood sizes, egg hatchability(0.1, 1 and 10 mg/L), and egg-laying rate(1 and 10 mg/L), and increased numbers of fertilized eggs in the uterus(1 and 10 mg/L). DEHP also caused damage to gonad development. DEHP decreased the total number of germline cells, and decreased the relative area of the gonad arm of all exposure groups, with worms in the 1 mg/L DEHP exposure group having the minimum gonad arm area. Additionally, DEHP caused a significant concentration-dependent increase in the expression of unc-86. Autophagy and ROS contributed to the enhancement of DEHP toxicity in reducing reproductive capacity, and glutathione peroxidase and superoxide dismutase were activated as the antioxidant defense in this study. Hence, we found that DEHP has a dual effect on nematodes. Higher concentration(10 mg/L) DEHP can inhibit the expression of autophagy genes( atg-18, atg-7, bec-1, lgg-1 and unc-51), and lower concentrations(0.1 and 1 mg/L) can promote the expression of autophagy genes. Our data highlight the potential environmental risk of DEHP in inducing reproductive toxicity toward the gonad development and reproductive capacity of environmental organisms.
基金supported by the National Natural Science Foundation of China,No.81571114 and 81771267(to ZH)the National Science Funds for Distinguished Youth Scholars of China,No.81325007(to XMJ)+2 种基金the Distinguished Professor of Cheung Kong Scholars Program in China,No.T2014251(to XMJ)the Wenzhou Municipal Sci-Tec Bureau Programs in China,No.Y20120154(to ZZ) and Y20140686(to ZH)the Projects of International Cooperation and Exchanges National Natural Science Foundation of China,No.81620108011(to XMJ)
文摘We previously demonstrated that administering 2-（2-benzofuranyl）-2-imidazolin（2-BFI）, an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by Wenzhou Medical University in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI（3 mg/kg） through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa＇s method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy. The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling（TUNEL） assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following： Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.
