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5. Modified citrus pectin ameliorates methotrexate-induced hepatic and pulmonary toxicity: role of Nrf2, galectin-3/TLR-4/NF-κB/TNF-α and TGF-β signaling pathways.

Author

Ismail, Randa, Habib, Heba A., Anter, Aliaa F., Amin, Amr, and Heeba, Gehan H.

Subjects
CYTOTOXINS, HEPATOTOXICOLOGY, INTRAPERITONEAL injections, SUPEROXIDE dismutase, CELLULAR signal transduction
Abstract

Introduction: Methotrexate (MTX) is a frequently utilized anti-inflammatory and anticancer agent. Its potential liver and lung toxicity often limits its clinical effectiveness. We conducted this study to demonstrate the possible protective impacts of a natural galectin-3 (Gal-3) inhibitor, modified citrus pectin (MCP), against MTX-induced liver and lung toxicity and verify the potential signaling pathways of these suggested effects. In vitro , the cytotoxicity of MCP and its modulatory effect on MTX cytotoxic efficacy were assessed. Methods: Four groups of rats were used: control, MTX (40 mg/kg, single intraperitoneal injection on day 9), MTX + MCP (200 mg/kg/day, orally, for 2 weeks), and MCP alone. MCF7, Nalm6, and JEG3 cell lines were used for the in vitro cytotoxicity assay. Results: MCP counteracted liver and lung toxicity evidenced by ameliorating the markers of liver and lung functions. Moreover, MCP minimized oxidative stress elicited by MTX in lung and liver tissues, as indicated by reduced malondialdehyde levels, elevated levels of reduced glutathione, increased superoxide dismutase activity, and upregulated Nrf2 protein expression. In hepatic and pulmonary tissues, MCP downregulated the inflammatory signaling pathway, Gal-3/TLR-4/NF-κB/TNF-α. MCP pretreatment decreased TGF-β, collagen content, and cleaved caspase-3 levels. MCP enhanced the cytotoxicity of MTX in Nalm6 and JEG3 and did not interfere with its cytotoxicity in the MCF7 cell lines. Discussion: MCP attenuated MTX-induced liver and lung toxicity through antioxidant, anti-fibrotic, anti-inflammatory, and anti-apoptotic influences, as demonstrated by the improved histopathological changes induced by MTX in pulmonary and hepatic tissues. Moreover, it increased MTX cytotoxicity in different human cell lines. [ABSTRACT FROM AUTHOR]

Published
2025
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6. RETRACTED: Alhakamy et al. Optimized Ellagic Acid–Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats. Biomolecules 2020, 10, 1006

Author

Alhakamy, Nabil A., primary, Badr-Eldin, Shaimaa M., additional, Ahmed, Osama A. A., additional, Halwani, Abdulrahman A., additional, Aldawsari, Hibah M., additional, El-Moselhy, Mohamed A., additional, Anter, Aliaa, additional, Sharkawi, Sara S., additional, Sultan, Muhammad H., additional, Madkhali, Osama A. A., additional, Bakhrebah, Muhammed A., additional, Alomary, Mohammad N., additional, Abdulaal, Wesam H., additional, and Fahmy, Usama A., additional

Published
2024
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11. Corrigendum to “Ketogenic diet restores hormonal, apoptotic/proliferative balance and enhances the effect of metformin on a letrozole-induced polycystic ovary model in rats” [Life Sci. 313 (2022) 121285]

Author

Ahmed, Al-Shaimaa F., primary, Sharkawi, Sara S., additional, AbdelHameed, Sara S., additional, Bayoumi, Asmaa M., additional, Moussa, Rabab S., additional, Alhakamy, Nabil A., additional, Al Sadoun, Hadeel, additional, Mansouri, Rasha A., additional, El-Moselhy, Mohamed A., additional, El-Daly, Mahmoud, additional, and Anter, Aliaa F., additional

Published
2023
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13. Corrigendum: The severity of acute kidney and lung injuries induced by cecal ligation and puncture is attenuated by menthol: Role of proliferating cell nuclear antigen and apoptotic markers

Author

Anter, Aliaa, primary, Ahmed, Al-Shaimaa F., additional, Hammad, Asmaa S. A., additional, Almalki, Waleed Hassan, additional, Abdel Hafez, Sara Mohamed Naguib, additional, Kasem, AlShaimaa W., additional, El-Moselhy, Mohamed A., additional, Alrabia, Mohammad W., additional, Ibrahim, Ahmed R. N., additional, and El-Daly, Mahmoud, additional

Published
2022
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14. Brassica oleracea L. var. botrytis Leaf Extract Alleviates Gentamicin-Induced Hepatorenal Injury in Rats—Possible Modulation of IL-1β and NF-κB Activity Assisted with Computational Approach

Author

Khalil, Hany Ezzat, primary, Abdelwahab, Miada F., additional, Emeka, Promise Madu, additional, Badger-Emeka, Lorina I., additional, Ahmed, Al-Shaimaa F., additional, Anter, Aliaa F., additional, Abdel Hafez, Sara Mohamed Naguib, additional, AlYahya, Khalid A., additional, Ibrahim, Hairul-Islam Mohamed, additional, Thirugnanasambantham, Krishnaraj, additional, Matsunami, Katsuyoshi, additional, and Ibrahim Selim, Alyaa Hatem, additional

Published
2022
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15. Chemical Composition and Valorization of Broccoli Leaf By-Products (Brassica oleracea L. Variety: Italica) to Ameliorate Reno-Hepatic Toxicity Induced by Gentamicin in Rats

Author

Khalil, Hany Ezzat, primary, Abdelwahab, Miada F., additional, Emeka, Promise Madu, additional, Badger-Emeka, Lorina I., additional, Abdel Hafez, Sara Mohamed Naguib, additional, AlYahya, Khalid A., additional, Ahmed, Al-Shaimaa F., additional, Anter, Aliaa F., additional, Abdel-Wahab, Nada M., additional, Matsunami, Katsuyoshi, additional, and Ibrahim Selim, Alyaa Hatem, additional

Published
2022
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16. The Severity of Acute Kidney and Lung Injuries Induced by Cecal Ligation and Puncture Is Attenuated by Menthol: Role of Proliferating Cell Nuclear Antigen and Apoptotic Markers

Author

Anter, Aliaa, primary, Ahmed, Al-Shaimaa F., additional, Hammad, Asmaa S. A., additional, Almalki, Waleed Hassan, additional, Abdel Hafez, Sara Mohamed Naguib, additional, Kasem, AlShaimaa W., additional, El-Moselhy, Mohamed A., additional, Alrabia, Mohammad W., additional, Ibrahim, Ahmed R. N., additional, and El-Daly, Mahmoud, additional

Published
2022
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17. Dihydromyricetin Modulates Nrf2 and NF-κB Crosstalk to Alleviate Methotrexate-Induced Lung Toxicity.

Author

Matouk, Asmaa I., Awad, Eman M., El-Tahawy, Nashwa F. G., El-Sheikh, Azza A. K., and Anter, Aliaa

Subjects
NUCLEAR factor E2 related factor, PULMONARY fibrosis, REGULATOR genes, LUNGS, LABORATORY rats, FLAVONOIDS
Abstract

Background: Methotrexate (MTX) is an effective anticancer, anti-inflammatory, and immunomodulatory agent. However, it induces a serious pneumonitis that leads to irreversible fibrotic lung damage. This study addresses the protective role of the natural flavonoid dihydromyricetin (DHM) against MTX-induced pneumonitis via modulation of Nrf2/NF-κB signaling crosstalk. Methods: Male Wistar rats were divided into 4 groups: control, which received the vehicle; MTX, which received a single MTX (40 mg/kg, i.p) at day 9 of the experiment; (MTX + DHM), which received oral DHM (300 mg/kg) for 14 days and methotrexate (40 mg/kg, i.p) on the 9th day; and DHM, which received DHM (300 mg/kg, p.o) for 14 days. Results: Lung histopathological examination and scoring showed a decline in MTX-induced alveolar epithelial damage and decreased inflammatory cell infiltration by DHM treatment. Further, DHM significantly alleviated the oxidative stress by decreasing MDA while increasing GSH and SOD antioxidant levels. Additionally, DHM suppressed the pulmonary inflammation and fibrosis through decreasing levels of NF-κB, IL-1β, and TGF-β1 while promoting the expression of Nrf2, a positive regulator of antioxidant genes, and its downstream modulator, HO-1. Conclusion: This study identified DHM as a promising therapeutic target against MTX-induced pneumonitis via activation of Nrf2 antioxidant signaling while suppressing the NF-κB mediated inflammatory pathways. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Optimized Self-Nanoemulsifying Delivery System Based on Plant-Derived Oil Augments Alpha-Lipoic Acid Protective Effects Against Experimentally Induced Gastric Lesions

Author

Badr-Eldin, Shaimaa M., primary, Fahmy, Usama A., additional, Aldawsari, Hibah M., additional, Ahmed, Osama A. A., additional, Alhakamy, Nabil A., additional, Okbazghi, Solomon Z., additional, El-Moselhy, Mohamed A., additional, Alghaith, Adel F., additional, Anter, Aliaa, additional, Matouk, Asmaa I., additional, Mahdi, Wael Ali, additional, Alshehri, Sultan, additional, and Bakhaidar, Rana, additional

Published
2021
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19. Optimized Ellagic Acid–Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats

Author

Alhakamy, Nabil A., primary, Badr-Eldin, Shaimaa M., additional, Ahmed, Osama A. A., additional, Halwani, Abdulrahman A., additional, Aldawsari, Hibah M., additional, El-Moselhy, Mohamed A., additional, Anter, Aliaa, additional, Sharkawi, Sara S., additional, Sultan, Muhammad H., additional, Madkhali, Osama A. A., additional, Bakhrebah, Muhammed A., additional, Alomary, Mohammad N., additional, Abdulaal, Wesam H., additional, and A. Fahmy, Usama, additional

Published
2020
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