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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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Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
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Laboratories Technology Department, Turabah University College, Taif University, Turabah 21995, Saudi Arabia
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Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
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Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
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Department of Pharmacology, Faculty of Pharmacy, Misurata University, Misurata 2478, Libya
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Department of Chemistry, Faculty of Pharmacy, Misurata University, Misurata 2478, Libya
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Laboratories Technologie Department, Turaba University College, Taif University, Turabah 21995, Saudi Arabia
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Pharmaceutical and Industrial Department, Faculty of Pharmacy, Misurata University, Misurata 2478, Libya
*
Authors to whom correspondence should be addressed.
Toxins 2019, 11(11), 642; https://doi.org/10.3390/toxins11110642
Received: 23 September 2019 / Revised: 29 October 2019 / Accepted: 30 October 2019 / Published: 4 November 2019
(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)
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–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-α 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. View Full-Text
Keywords: Euphorbia peplus; MDM2-p53; apoptosis; anticancer; di-(2-ethylhexyl) phthalate Euphorbia peplus; MDM2-p53; apoptosis; anticancer; di-(2-ethylhexyl) phthalate
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MDPI and ACS Style

Abd-Elhakim, Y.M.; Abdo Nassan, M.; Salem, G.A.; Sasi, A.; Aldhahrani, A.; Ben Issa, K.; Abdel-Rahman Mohamed, A. Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats. Toxins 2019, 11, 642.

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