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

• Published in: Antioxidants 2019-09, Vol.8 (9), p.415
• Main Authors: Ghareeb, Mosad A., Sobeh, Mansour, El-Maadawy, Walaa H., Mohammed, Hala Sh, Khalil, Heba, Botros, Sanaa, Wink, Michael
• Format: Article
• Language: English
• Subjects: anti-inflammatory; antioxidant; Antioxidants; Apoptosis; Benzoic acid; Carbonyl compounds; Caspase-3; Creatinine; Cyclophosphamide; Cytotoxicity; Eucalyptus globulus; Gallic acid; Gene expression; hepatotoxicity; High-performance liquid chromatography; Inflammation; Interleukin 6; Kidneys; Laboratory animals; Leaves; Lipid peroxidation; Liver; Metabolites; nephrotoxicity; NF-κB protein; Nitric oxide; Nrf2/HO-1 signaling; Plant extracts; polyphenolics; Polyphenols; Proteins; Reagents; Secondary metabolites; Toxicity; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Urea
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox8090415

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.