کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5562051 | 1562595 | 2017 | 36 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice
ترجمه فارسی عنوان
مهار کانسیکین همی کانال باعث کاهش آسیب کبدی ناشی از استامینوفن در موش می شود
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کلمات کلیدی
FRAP2-APBCBXNAPQIN-acetyl-p-benzoquinone imineAPAPHBSSALTGSSGGSHtransactivator of transcriptionTNFαAdenosine Triphosphate - آدنوزین تری فسفاتATP - آدنوزین تری فسفات یا ATPAlanine aminotransferase - آلانین آمینوترانسفرازProbability - احتمالات، احتمالAcetaminophen - استامینوفن inflammation - التهاب( توروم) TAT - تاتanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceEnzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاtumor necrosis factor α - تومور نکروز عامل αstandard error of the mean - خطای استاندارد میانگینHepatotoxicity - سمیت کبدgap junction - فاصله ی شکافfluorescence recovery after photobleaching - فلوئورسانس پس از فوتوبلاسیکHank’s balanced salt solution - محلول نمک متعادل هانکSEM - مدل معادلات ساختاری / میکروسکوپ الکترونی روبشیHemichannel - همیشلcarbenoxolone - کاربن اکسولونconnexin - کنسکسینGlutathione - گلوتاتیونglutathione disulfide - گلوتاتیون دی سولفید
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen. Prior to this, in vitro testing was performed to confirm the specificity and efficacy of TAT-Gap24 and TAT-Gap19 in blocking connexin32 and connexin43 hemichannels, respectively. Subsequently, mice were overdosed with acetaminophen followed by treatment with TAT-Gap24 or TAT-Gap19 or a combination of both after 1.5Â h. Sampling was performed 3, 6, 24 and 48Â h following acetaminophen administration. Evaluation of the effects of connexin hemichannel inhibition was based on a series of clinically relevant read-outs, measurement of inflammatory cytokines and oxidative stress. Subsequent treatment of acetaminophen-overdosed mice with TAT-Gap19 only marginally affected liver injury. In contrast, a significant reduction in serum alanine aminotransferase activity was found upon administration of TAT-Gap24 to intoxicated animals. Furthermore, co-treatment of acetaminophen-overdosed mice with both peptides revealed an additive effect as even lower serum alanine aminotransferase activity was observed. Blocking of connexin32 or connexin43 hemichannels individually was found to decrease serum quantities of pro-inflammatory cytokines, while no effects were observed on the occurrence of hepatic oxidative stress. This study shows for the first time a role for connexin hemichannels in acetaminophen-induced acute liver failure.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 278, 15 August 2017, Pages 30-37
Journal: Toxicology Letters - Volume 278, 15 August 2017, Pages 30-37
نویسندگان
Michaël Maes, Sara Crespo Yanguas, Joost Willebrords, James L. Weemhoff, Tereza Cristina da Silva, Elke Decrock, Margitta Lebofsky, Isabel Veloso Alves Pereira, Luc Leybaert, Anwar Farhood, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken,