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Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato–Renal Protective Potential Against Cyclophosphamide Induced Toxicity in Mice

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Medicinal Chemistry Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt
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Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 44883-2462 Heidelberg, Germany
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AgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660–Hay MoulayRachid, 43150 Ben-Guerir, Morocco
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Pharmacology Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt
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Department of Pharmacognosy, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11311, Egypt
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Pathology Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt
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Authors to whom correspondence should be addressed.
Antioxidants 2019, 8(9), 415; https://doi.org/10.3390/antiox8090415
Received: 3 July 2019 / Revised: 17 August 2019 / Accepted: 19 August 2019 / Published: 19 September 2019
Cyclophosphamide (CP) is a potent anti-neoplastic and immunosuppressive agent; however, it causes multi-organ toxicity. We elucidated the protective activities of Eucalyptus globulus (EG) leaf extract against CP-induced hepato–renal toxicity. Mice were treated with EG for 15 days plus CP on day 12 and 13 of the experiment. Using HPLC-DAD-ESI-MS/MS, 26 secondary metabolites were identified in EG leaf extract. Out of them, 4 polyphenolic compounds were isolated: (1) 4-(O-β-d-xylopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (2) 4-(O-α-l-rhamnopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (3) gallic acid, and (4) methyl gallate. Effects of EG extract on biochemical parameters, gene expression, and immune-histopathological changes were assessed in comparison to mesna positive control. Results showed that EG improved CP-increased serum ALT, AST, creatinine, and blood urea nitrogen levels. The hepatic and renal tissue levels of MDA, nitric oxide, protein carbonyl, TNF-α, IL-6, and immunohistochemical expression of nuclear factor kappa-B (NF-kB) and caspase-3 were reduced. Also, hepatic and renal GSH contents, and nuclear factor E2-related factor 2 (NRf2)/ hemoxygenase-1 (HO-1) signaling levels were increased. Histopathological findings supported our findings where hepatic and renal architecture were almost restored. Results revealed the protective effects of EG against CP-induced hepato–renal toxicity. These effects may be related to EG antioxidant, anti-inflammatory, and anti-apoptotic properties coupled with activation of Nrf2/HO-1 signaling. View Full-Text
Keywords: Eucalyptus globulus; polyphenolics; cyclophosphamide; hepatotoxicity; nephrotoxicity; antioxidant; anti-inflammatory; Nrf2/HO-1 signaling Eucalyptus globulus; polyphenolics; cyclophosphamide; hepatotoxicity; nephrotoxicity; antioxidant; anti-inflammatory; Nrf2/HO-1 signaling
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Ghareeb, M.A.; Sobeh, M.; El-Maadawy, W.H.; Mohammed, H.S.; Khalil, H.; Botros, S.; Wink, M. Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato–Renal Protective Potential Against Cyclophosphamide Induced Toxicity in Mice. Antioxidants 2019, 8, 415.

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