Open access · Peer reviewed · No APCs
Original ArticleIndian Journal of Pharmaceutical Education and ResearchVol. 55 | Issue 4 | 2021 | pp. 1066–1073Open access
Protection of Hesperidin against Methotrexate-Induced Nephrotoxicity may be Mediated by Nrf2/HO-1 Pathway
- 1,2*,
- 2,3,
- 4,5,
- 6
- 1 Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.
- 2 Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, EGYPT.
- 3 Basic Health Sciences Department, Faculty of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAUDI ARABIA.
- 4 Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, SAUDI ARABIA.
- 5 Department of Biochemistry, Faculty of Pharmacy, Minia University, El-Minia, EGYPT.
- 6 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, EGYPT.
Published in Indian Journal of Pharmaceutical Education and Research
Correspondence: Mohamed Aly Morsy
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.; Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, EGYPT.
Email: momorsy@kfu.edu.sa
Copyright: © 2021 Manuscript Technomedia. This is an open access article.
- Published:
- Jan 21, 2021
- Received:
- Sep 15, 2021
- Accepted:
- Nov 17, 2021
How to cite
Morsy, M. A., El-Sheikh, A. A. K., Ibrahim, A. R. N., & El-Daly, M. (2021). Protection of Hesperidin against Methotrexate-Induced Nephrotoxicity may be Mediated by Nrf2/HO-1 Pathway. Indian Journal of Pharmaceutical Education and Research, 55(4), 1066–1073. https://doi.org/10.5530/ijper.55.4.207
Abstract
Background: Methotrexate (MTX), a successfully used chemotherapeutic in the treatment of various malignancies and autoimmune diseases, might cause severe nephrotoxicity. Here, we aimed at investigating possible nephroprotective effects of hesperidin (HES), a flavanone present in citrus fruits, against MTX-induced toxicity. Methods: Rats were divided into control, HES, MTX, and MTX/HES groups, where HES was administered in a dose of 100 mg/kg/day orally for 8 days and MTX in a single i.p. dose of 20 mg/kg on day 5 of the experiment. Results: Pretreatment with HES significantly improved MTX-induced deteriorated kidney function and structure, as well as reversed MTX effects on renal tumor necrosis factor (TNF)-α level and caspase 3 expression. MTX upregulated renal breast cancer resistance protein (BCRP); an efflux transporter that extrudes MTX from the kidney. Unfortunately, MTX/HES did not show a further increase in BCRP expression but rather showed downregulation. MTX also caused downregulation of renal nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) expressions, whereas HES reversed the MTX effect and upregulated renal Nrf2/HO-1. Conclusion: HES conferred protection against MTX-mediated nephrotoxicity, at least in part via anti-inflammatory and anti-apoptotic mechanisms. Nrf2/HO-1 pathway, but not BCRP, may have a role in HES-induced nephroprotection against MTX toxicity.
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Article metadata
| Title | Protection of Hesperidin against Methotrexate-Induced Nephrotoxicity may be Mediated by Nrf2/HO-1 Pathway |
|---|---|
| Authors | Mohamed Aly Morsy; Azza Ali Kamel El-Sheikh; Ahmed Ragaa Nour Ibrahim; Mahmoud El-Daly |
| Affiliations | Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.; Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, EGYPT.; Basic Health Sciences Department, Faculty of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAUDI ARABIA.; Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, SAUDI ARABIA.; Department of Biochemistry, Faculty of Pharmacy, Minia University, El-Minia, EGYPT.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, EGYPT. |
| Corresponding author | momorsy@kfu.edu.sa |
| Journal | Indian Journal of Pharmaceutical Education and Research |
| Volume / Issue | Vol. 55, Issue 4 (2021) |
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