Abstract：
BACKGROUND: Toxic cardiomyopathies were a potentially fatal adverse effect of anthracycline therapy.
OBJECTIVE: This study was conducted to demonstrate the pathogenetic, morphologic, and toxicologic effects of doxorubicin on the heart and to investigate how the MAPK /TNF-α pathway can be modulated to improve doxorubicin-Induced cardiac lesions using bone marrow-derived mesenchymal stem cells (BM-MSCs) and olive leaf extract (OLE).
METHODS: During the study, 40 adult male rats were used. Ten were used to donate MSCs, and the other 30 were split into 5 equal groups: Group I was the negative control, Group II obtained oral OLE, Group III obtained an intraperitoneal cumulative dose of DOX (12 mg/kg) in 6 equal doses of 2 mg/kg every 48 h for 12 days, Group IV obtained intraperitoneal DOX and oral OLE at the same time, and Group V obtained intraperitoneal DOX and BM-MSCs through the tail vein at the same time for 12 days. Four weeks after their last dose of DOX, the rats were euthanized. By checking the bioinformatic databases, a molecularly targeted path was selected. Then the histological, immunohistochemistry, and gene expression of ERK, JNK, NF-κB, IL-6, and TNF-α were done.
RESULTS: Myocardial immunohistochemistry revealed severe fibrosis, cell degeneration, increased vimentin, and decreased CD-31 expression in the DOX-treated group, along with a marked shift in morphometric measurements, a disordered ultrastructure, and overexpression of inflammatory genes (ERK, NF-κB, IL-6, and TNF-α), oxidative stress markers, and cardiac biomarkers. Both groups IV and V displayed reduced cardiac fibrosis or inflammation, restoration of the microstructure and ultrastructure of the myocardium, downregulation of inflammatory genes, markers of oxidative stress, and cardiac biomarkers, a notable decline in vimentin, and an uptick in CD-31 expression. In contrast to group IV, group V showed a considerable beneficial effect.
CONCLUSIONS: Both OLE and BM-MSCs showed an ameliorating effect in rat models of DOX-induced cardiotoxicity, with BM-MSCs showing a greater influence than OLE.
OBJECTIVE: This study was conducted to demonstrate the pathogenetic, morphologic, and toxicologic effects of doxorubicin on the heart and to investigate how the MAPK /TNF-α pathway can be modulated to improve doxorubicin-Induced cardiac lesions using bone marrow-derived mesenchymal stem cells (BM-MSCs) and olive leaf extract (OLE).
METHODS: During the study, 40 adult male rats were used. Ten were used to donate MSCs, and the other 30 were split into 5 equal groups: Group I was the negative control, Group II obtained oral OLE, Group III obtained an intraperitoneal cumulative dose of DOX (12 mg/kg) in 6 equal doses of 2 mg/kg every 48 h for 12 days, Group IV obtained intraperitoneal DOX and oral OLE at the same time, and Group V obtained intraperitoneal DOX and BM-MSCs through the tail vein at the same time for 12 days. Four weeks after their last dose of DOX, the rats were euthanized. By checking the bioinformatic databases, a molecularly targeted path was selected. Then the histological, immunohistochemistry, and gene expression of ERK, JNK, NF-κB, IL-6, and TNF-α were done.
RESULTS: Myocardial immunohistochemistry revealed severe fibrosis, cell degeneration, increased vimentin, and decreased CD-31 expression in the DOX-treated group, along with a marked shift in morphometric measurements, a disordered ultrastructure, and overexpression of inflammatory genes (ERK, NF-κB, IL-6, and TNF-α), oxidative stress markers, and cardiac biomarkers. Both groups IV and V displayed reduced cardiac fibrosis or inflammation, restoration of the microstructure and ultrastructure of the myocardium, downregulation of inflammatory genes, markers of oxidative stress, and cardiac biomarkers, a notable decline in vimentin, and an uptick in CD-31 expression. In contrast to group IV, group V showed a considerable beneficial effect.
CONCLUSIONS: Both OLE and BM-MSCs showed an ameliorating effect in rat models of DOX-induced cardiotoxicity, with BM-MSCs showing a greater influence than OLE.
摘要：
背景：中毒性心肌病是蒽环类药物治疗的潜在致命不良反应。
目的：本研究的目的是，形态学,和多柔比星对心脏的毒理学作用，并研究如何使用骨髓间充质干细胞（BM-MSCs）和橄榄叶提取物（OLE）调节MAPK/TNF-α途径以改善多柔比星诱导的心脏损伤。
方法：在研究期间，使用40只成年雄性大鼠。十个被用来捐赠MSC，其余30只分为5组：第一组为阴性对照，II组获得口服OLE，第III组获得腹膜内累积剂量的DOX（12mg/kg），每48小时6个相等剂量的2mg/kg，持续12天，IV组同时获得腹腔DOX和口服OLE，第五组同时通过尾静脉获得腹腔DOX和BM-MSCs，持续12天。在他们最后一次服用DOX后四周，对大鼠实施安乐死。通过检查生物信息学数据库，选择分子靶向路径。然后组织学，免疫组织化学，和ERK的基因表达，JNK,NF-κB,进行IL-6和TNF-α。
结果：心肌免疫组化显示严重纤维化，细胞变性，增加波形蛋白，和减少CD-31表达在DOX处理组，随着形态测量的明显变化，无序的超微结构，和炎症基因的过度表达（ERK，NF-κB,IL-6和TNF-α），氧化应激标志物，和心脏生物标志物。IV组和V组均显示心脏纤维化或炎症减少，心肌的微观结构和超微结构的恢复，炎症基因的下调，氧化应激的标志物，和心脏生物标志物，波形蛋白的显著下降，和CD-31表达的上升。与IV组相比，组V表现出相当的有益效果。
结论：OLE和BM-MSCs在DOX诱导的大鼠心脏毒性模型中均有改善作用，BM-MSCs显示出比OLE更大的影响。
目的：本研究的目的是，形态学,和多柔比星对心脏的毒理学作用，并研究如何使用骨髓间充质干细胞（BM-MSCs）和橄榄叶提取物（OLE）调节MAPK/TNF-α途径以改善多柔比星诱导的心脏损伤。
方法：在研究期间，使用40只成年雄性大鼠。十个被用来捐赠MSC，其余30只分为5组：第一组为阴性对照，II组获得口服OLE，第III组获得腹膜内累积剂量的DOX（12mg/kg），每48小时6个相等剂量的2mg/kg，持续12天，IV组同时获得腹腔DOX和口服OLE，第五组同时通过尾静脉获得腹腔DOX和BM-MSCs，持续12天。在他们最后一次服用DOX后四周，对大鼠实施安乐死。通过检查生物信息学数据库，选择分子靶向路径。然后组织学，免疫组织化学，和ERK的基因表达，JNK,NF-κB,进行IL-6和TNF-α。
结果：心肌免疫组化显示严重纤维化，细胞变性，增加波形蛋白，和减少CD-31表达在DOX处理组，随着形态测量的明显变化，无序的超微结构，和炎症基因的过度表达（ERK，NF-κB,IL-6和TNF-α），氧化应激标志物，和心脏生物标志物。IV组和V组均显示心脏纤维化或炎症减少，心肌的微观结构和超微结构的恢复，炎症基因的下调，氧化应激的标志物，和心脏生物标志物，波形蛋白的显著下降，和CD-31表达的上升。与IV组相比，组V表现出相当的有益效果。
结论：OLE和BM-MSCs在DOX诱导的大鼠心脏毒性模型中均有改善作用，BM-MSCs显示出比OLE更大的影响。
