Chemical profiling of polyphenolics in Eucalyptus globulus and evaluation of its hepato-renal protective potential against cyclophosphamide induced toxicity in mice
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 o...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 September 2019
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| In: |
Antioxidants
Year: 2019, Volume: 8, Issue: 9 |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox8090415 |
| Online Access: | Verlag, Volltext: https://doi.org/10.3390/antiox8090415 Verlag: https://www.mdpi.com/2076-3921/8/9/415 
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| Author Notes: | Mosad A. Ghareeb, Mansour Sobeh, Walaa H. El-Maadawy, Hala Sh Mohammed, Heba Khalil, Sanaa Botros and Michael Wink |
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| 520 | |a 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. | ||
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