Hemin versus erythropoietin : Possible role in Nrf2/HO-1 signaling pathway in rats with nephrotoxicity
Copyright © 2022. Published by Elsevier Masson SAS..
BACKGROUND AND AIM: Gentamycin-induced nephrotoxicity is related to stimulation of oxidative stress and inflammatory cascades leading to apoptotic renal damage. Heme oxygenase-1 (HO-1) induction considered to be an adaptive response against oxidative tissue damage. Our study aimed to investigate the possible nephroprotective role of HO-1 inducers (hemin and erythropoietin (EPO)) and elucidate their potential underlying molecular mechanisms by assessing their antioxidant, anti-apoptotic, and anti-inflammatory properties.
METHODS: Kidney function markers (urea and creatinine), lipid peroxidation and antioxidant markers (MDA and GPx), inflammation and apoptotic markers (IL-6 and Bcl-2), and the relative gene expression levels of Nrf2 and HO-1 were assessed. Histopathological changes of the kidney were examined.
RESULTS: Nephrotoxic rats pretreated with hemin showed significant decrease in serum level of urea, creatinine, and MDA, compared to non-treated group. The kidney tissues also showed significant elevation of Bcl2 level, but significant decrease of IL-6, compared to non-treated group. Moreover, hemin pre-treatment significantly upregulated gene expression of Nrf2 and HO-1 in kidney tissue to near the normal control group. On the other hand, pretreatment with EPO showed significant upregulation of HO-1 gene expression but didn't show significant difference in Nrf2 gene expression compared to control group. The histopathological examination of kidney supported the biochemical results.
CONCLUSION: The current results proved that hemin rather than EPO, showed reno-protective effects in rats, which was mediated by activation of Nrf2 signaling pathway. This could be also attributed to the observed anti-inflammatory, antioxidant, and anti-apoptotic properties of hemin. In this regard, EPO showed lower potency.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:156 |
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| Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 156(2022) vom: 10. Dez., Seite 113971 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
El-Ashmawy, Nahla E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.12.2022 Date Revised 12.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biopha.2022.113971 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM349248028 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022. Published by Elsevier Masson SAS. | ||
| 520 | |a BACKGROUND AND AIM: Gentamycin-induced nephrotoxicity is related to stimulation of oxidative stress and inflammatory cascades leading to apoptotic renal damage. Heme oxygenase-1 (HO-1) induction considered to be an adaptive response against oxidative tissue damage. Our study aimed to investigate the possible nephroprotective role of HO-1 inducers (hemin and erythropoietin (EPO)) and elucidate their potential underlying molecular mechanisms by assessing their antioxidant, anti-apoptotic, and anti-inflammatory properties | ||
| 520 | |a METHODS: Kidney function markers (urea and creatinine), lipid peroxidation and antioxidant markers (MDA and GPx), inflammation and apoptotic markers (IL-6 and Bcl-2), and the relative gene expression levels of Nrf2 and HO-1 were assessed. Histopathological changes of the kidney were examined | ||
| 520 | |a RESULTS: Nephrotoxic rats pretreated with hemin showed significant decrease in serum level of urea, creatinine, and MDA, compared to non-treated group. The kidney tissues also showed significant elevation of Bcl2 level, but significant decrease of IL-6, compared to non-treated group. Moreover, hemin pre-treatment significantly upregulated gene expression of Nrf2 and HO-1 in kidney tissue to near the normal control group. On the other hand, pretreatment with EPO showed significant upregulation of HO-1 gene expression but didn't show significant difference in Nrf2 gene expression compared to control group. The histopathological examination of kidney supported the biochemical results | ||
| 520 | |a CONCLUSION: The current results proved that hemin rather than EPO, showed reno-protective effects in rats, which was mediated by activation of Nrf2 signaling pathway. This could be also attributed to the observed anti-inflammatory, antioxidant, and anti-apoptotic properties of hemin. In this regard, EPO showed lower potency | ||
| 650 | 4 | |a Journal Article | |
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