Browsing by Author "Jehane I. Eid"
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Item Therapeutic Effect of Melatonin and/or Adipose-Derived Mesenchymal Stem Cells Against Doxorubicin-Induced Renal Toxicity in Wister Rats(Institute of Advanced Studies, 2024-07-22) Romisaa Hussein Sayed; Emad M. El Zayat; Sherein S. Abdelgayed3; Jehane I. Eid; Mohamed HosneyDoxorubicin (DOX) is highly effective against cancer, but its use is limited due to significant toxicity, particularly in the liver and kidneys. This toxicity is primarily caused by oxidative stress, which results in biochemical, histological, and genetic abnormalities, and disrupts the body's antioxidant defenses. Adipose-derived mesenchymal stem cells (ADMSCs) show promise in cell therapy applications against DOX toxicity Similarly, melatonin supplementation has demonstrated therapeutic potential in mitigating DOX-induced liver and kidney damage by reducing oxidative stress. Understanding and harnessing these therapeutic effects could lead to improved treatments for DOXinduced organ damage. Aims: This study focused on evaluating how melatonin and adipose-derived mesenchymal stem cells (ADMSCs) could mitigate renal toxicity induced by doxorubicin (DOX), a potent anthracycline chemotherapeutic drug known for its severe side effects. The research aimed to explore whether the antioxidant properties of melatonin and the regenerative capabilities of ADMSCs could synergistically alleviate the adverse effects of DOX on renal function in Wistar rats. Methods: The study included two main groups: a control group receiving saline and a DOX group receiving six doses of doxorubicin to induce renal toxicity. Subsequently, rats from both groups were assigned to receive treatments of saline, ADMSCs, melatonin, or a combination of ADMSCs and melatonin. Rats were euthanized at different time points post-treatment, and blood and kidney tissue samples were collected. The analysis included assessment of oxidative stress biomarkers, DNA damage, gene expression profiles, histopathological changes, and cell homing in the kidney tissues. Results: DOX induces oxidative stress, inflammation, and genotoxicity in kidneys while reducing antioxidant enzyme activity. Melatonin and/or ADMSC treatments effectively mitigate these effects by decreasing oxidative stress, inflammation, and DNA damage. The protective mechanisms involve modulation of apoptosis pathways, evidenced by changes in p53 and Bcl2 expression levels, as well as assessment of double-strand breaks using the neutral comet assay, and also the improvement of the inflammatory markers IL-6 & IL- 10 evidenced by the histopathological results. Conclusion: Melatonin and ADMSCs demonstrate protective effects against DOX-induced renal toxicity, potentially enhancing chemotherapy safety by reducing renal damage. The synergistic benefits of combining melatonin and ADMSC therapy in improving chemotherapy tolerability warrant further investigation in preclinical models to optimize treatment strategies and validate efficacy before clinical application.Item β‑glucan nanoparticles alleviate acute asthma by suppressing ferroptosis and DNA damage in mice(Apoptosis : an international journal on programmed cell death , 2024-09-21) Bassam W. Ebeed; Islam Ahmed Abdelmawgood; Mohamed A. Kotb; Noha A. Mahana; Ayman Saber Mohamed; Marwa A. Ramadan; Abeer Mahmoud Badr; Manar Nasr; Osama Mohsen Qurani; Reem Mohamed Hamdy; Nada Yasser Abd El‑Hakiem; Mariam Khaled Fahim; Mariam Morris Fekry; Jehane I. EidAsthma is a severe respiratory disease marked by airway inflammation, remodeling, and oxidative stress. β-Glucan (BG), a polysaccharide constituent of fungal cellular structures, exhibits potent immunomodulatory activities. The investigational focus was on the anti-asthmatic and anti-ferroptotic properties of beta-glucan nanoparticles (BG-NPs) in a murine model of allergic asthma induced by ovalbumin (OVA). BG was extracted from Chaga mushrooms (Inonotus obliquus), and its BGNPs were characterized utilizing techniques including FT-IR, UV visible spectroscopy, zeta potential analysis, DLS, XRD, and TEM. The Balb/C mice were allocated into five groups: control, untreated asthmatic, dexamethasone (Dexa)-treated (1 mg/kg), BG-treated (100 mg/kg), BG-NPs-treated (45 mg/kg), and BG-treated (100 mg/kg). Treatment with BG-NPs markedly diminished the entry of inflammatory cells into the respiratory passage, serum IgE concentrations, DNA damage, and markers of oxidative stress through the reduction of malonaldehyde (MDA) levels and enhancing the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). Furthermore, BG-NPs reduced iron deposition and promoted the transcriptional activity of the GPx4 gene in pulmonary cells, attenuating ferroptosis. The results demonstrated that BG-NPs reduced asthma by inhibiting oxidative stress, inflammation, DNA damage, and ferroptosis. Our results suggest that BG-NPs could be used as potential treatments for allergic asthma.