Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats
| العنوان: | Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats |
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| المؤلفون: | Mohamed Abdo Nassan, Khaled Ben Issa, Abdelkarim Sasi, Adil Aldhahrani, Gamal A. Salem, Yasmina M. Abd-Elhakim, Amany Abdel-Rahman Mohamed |
| المصدر: | Toxins Toxins, Vol 11, Iss 11, p 642 (2019) Volume 11 Issue 11 |
| بيانات النشر: | MDPI, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Cell Survival, Health, Toxicology and Mutagenesis, Aspartate transaminase, lcsh:Medicine, Pharmacology, Toxicology, Creatine, anticancer, Kidney, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Euphorbia peplus, In vivo, Euphorbia, Lactate dehydrogenase, medicine, Animals, Computer Simulation, Rats, Wistar, Linolenate, 030304 developmental biology, 0303 health sciences, Creatinine, biology, euphorbia peplus, Plant Extracts, Myocardium, lcsh:R, apoptosis, di-(2-ethylhexyl) phthalate, MDM2-p53, Heart, Proto-Oncogene Proteins c-mdm2, Rats, Molecular Docking Simulation, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, biology.protein, Creatine kinase, Tumor Suppressor Protein p53, Biomarkers |
| الوصف: | This study explored the probable in vivo cardiac and renal toxicities together with in silico approaches for predicting the apoptogenic potential of Euphorbia peplus methanolic extract (EPME) in rats. Cardiac and renal injury biomarkers were estimated with histopathological and immunohistochemical evaluations of both kidney and heart. The probable underlying mechanism of E. peplus compounds to potentiate p53 activity is examined using Molecular Operating Environment (MOE) docking software and validated experimentally by immunohistochemical localization of p53 protein in the kidney and heart tissues. The gas chromatography/mass spectrometry analysis of E. peplus revealed the presence of nine different compounds dominated by di-(2-ethylhexyl) phthalate (DEHP). Significant elevations of troponin, creatine phosphokinase, creatine kinase&ndash myocardium bound, lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, urea, creatinine, and uric acid were evident in the EPME treated rats. The EPME treated rats showed strong renal and cardiac p53 expression and moderate cardiac TNF-&alpha expression. Further, our in silico results predicted the higher affinity and good inhibition of DEHP, glyceryl linolenate, and lucenin 2 to the MDM2-p53 interface compared to the standard reference 15 a compound. Conclusively, EPME long-term exposure could adversely affect the cardiac and renal tissues probably due to their inflammatory and apoptotic activity. Moreover, the in silico study hypothesizes that EPME inhibits MDM2-mediated degradation of p53 suggesting possible anticancer potentials which confirmed experimental by strong p53 expression in renal and cardiac tissues. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6651 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3eba02fc325f735540460f0919dbf9b5Test http://europepmc.org/articles/PMC6891376Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3eba02fc325f735540460f0919dbf9b5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726651 |
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