Journal Article

Ameliorative effect of flavocoxid on cyclophosphamide-induced cardio and neurotoxicity via targeting the GM-CSF/NF-κB signaling pathway

Rizq, Mohamed R., Elsayed, Fatma F., Khalifa, Eman M., Elshenawy, Waad M., Abdelaziz, Rania R.

2022

Overview

Cyclophosphamide (Cyclo) is a chemotherapeutic agent used as an immunosuppressant and as a treatment for many cancerous diseases. Many previous pieces of literature proved the marked cardio and neurotoxicity of the drug. Thus, this research provides evidence on the alleviative effect of flavocoxid on the cardiac and brain toxicity of cyclophosphamide in mice and determines its underlying mechanisms. Flavocoxid (Flavo) is a potent antioxidant and anti-inflammatory agent that inhibits the peroxidase activity of cyclooxygenase (COX-1 and COX-2) enzymes and 5-lipooxygenase ( 5-LOX ). Flavo was administered orally (20 mg/kg) for 2 weeks, followed by Cyclo (100 mg/kg, i.p.) on day 14. Higher heart and brain weight indices, serum lactate dehydrogenase (LDH), creatine kinase (CK-MB), and nitric oxide (NO) were mitigated following Flavo administration. Flavo modulated oxidative stress biomarkers (malonaldehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD)), tumor necrosis factor-α (TNF - α), and interleukin (IL)-1β. Additionally, cardiac troponin I (cTn-I), nuclear factor kappa B (NF-κB), brain amyloid precursor protein (APP), and granulocyte macrophage colony-stimulating factor (GM-CSF) were decreased by Flavo administration. Moreover, Flavo ameliorated heart and brain histopathological changes and caspase-3 levels. Collectively, Flavo (20 mg/kg) for 14 days showed significant cardio and neuroprotective effects due to its antioxidant, anti-inflammatory, and antiapoptotic activities via modulation of oxidative stress, inflammation, and the GM-CSF/NF-κB signaling pathway.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Alzheimer's disease / amyloid / Amyloid beta-Protein Precursor - metabolism / Amyloid beta-Protein Precursor - pharmacology / Amyloid precursor protein / Animals / Anti-inflammatory agents / Anti-Inflammatory Agents - pharmacology / Antioxidants / Antioxidants - metabolism / Antioxidants - pharmacology / Aquatic Pollution / Atmospheric Protection/Air Quality Control/Air Pollution / Biomarkers / Biomarkers - metabolism / blood serum / Brain / Calcium-binding protein / Caspase 3 - metabolism / Caspase-3 / Catechin / Cerebrospinal fluid / Chemotherapy / Colony-stimulating factor / Creatine / Creatine kinase / Creatine Kinase - metabolism / Creatine Kinase - pharmacology / Cyclooxygenase 2 - metabolism / Cyclooxygenase-1 / Cyclooxygenase-2 / Cyclophosphamide / Cyclophosphamide - toxicity / Drug Combinations / drug therapy / Earth and Environmental Science / Ecotoxicology / Environment / Environmental Chemistry / Environmental Health / Environmental science / Glutathione / Glutathione - metabolism / Granulocyte-macrophage colony-stimulating factor / Granulocyte-Macrophage Colony-Stimulating Factor - metabolism / Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology / Heart / histopathology / Immunosuppressive Agents - pharmacology / Inflammation / Interleukins / Interleukins - metabolism / Kinases / L-Lactate dehydrogenase / Lactate dehydrogenase / Lactate Dehydrogenases - metabolism / Lactic acid / Liquid oxygen / Macrophage Colony-Stimulating Factor - metabolism / Macrophage Colony-Stimulating Factor - pharmacology / Malondialdehyde / Malondialdehyde - pharmacology / Mice / necrosis / neoplasms / Neuroprotection / Neuroprotective Agents - pharmacology / Neurotoxicity / NF-kappa B - metabolism / NF-κB protein / Nitric oxide / Nitric Oxide - pharmacology / Oxidative Stress / Peroxidase / Peroxidases - metabolism / prostaglandin synthase / Research Article / Signal Transduction / Signaling / Superoxide dismutase / Superoxide Dismutase - metabolism / Toxicity / transcription factor NF-kappa B / Troponin I - metabolism / Troponin I - pharmacology / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-TNF / Waste Water Technology / Water Management / Water Pollution Control