The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanism
Objectives: This study aimed to evaluate if the protective effect of Isoliquiritigenin (ISL) against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling. Methods: Adult male Wistart rats were treated as control, ISL, DOX, DOX, and ISL + DOX + ISL + Nrf2 inhibitor (brusatol)...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Journal of King Saud University: Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364722003469 |
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| author | Wahidah H. Al-Qahtani Ghedeir M. Alshammari Mohammad A. Alshuniaber Mureed Husain Sarah A. Alawwad Salwa T. Al-Ayesh Mohammed Abdo Yahya Abdulrahman S. Aldawood |
| author_facet | Wahidah H. Al-Qahtani Ghedeir M. Alshammari Mohammad A. Alshuniaber Mureed Husain Sarah A. Alawwad Salwa T. Al-Ayesh Mohammed Abdo Yahya Abdulrahman S. Aldawood |
| author_sort | Wahidah H. Al-Qahtani |
| collection | DOAJ |
| description | Objectives: This study aimed to evaluate if the protective effect of Isoliquiritigenin (ISL) against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling. Methods: Adult male Wistart rats were treated as control, ISL, DOX, DOX, and ISL + DOX + ISL + Nrf2 inhibitor (brusatol) (n = 8/group). Treatments with ISL (25 mg//kg, oral) were carried out 10 days before and 10 days after the single dose of DOX (15 mg/kg, i.p). Results: Treatment with ISL attenuated the glomerular and tubular damage and reduced interstitial fibrosis and collagen accumulation in the kidneys of DOX-intoxicated animals. It also increased urinary flow and volume, stimulated urinary creatinine excretion, and decreased albumin excretion. These effects were associated with high transcription of Bcl2, suppression of ROS, MDA, and inflammatory cytokines production (i.e., TNF-α, IL-6, and IL-1β), downregulation of apoptotic markers (Bax and caspase-3/9), TGF-β1, Collagen I/III. Besides, ISL stimulated renal expression, translation, and nuclear localization of Nrf2, as well as levels of GSH and SOD, independent of keap-1. All these effects afforded by ISL were reversed by suppressing Nrf2 with brusatol. Conclusion: Pre-treatment with ISL is an effective strategy to alleviate DOX-induced nephropathy in rats by stimulating the Nrf2/antioxidant axis, which encourages further pre-clinical studies. |
| first_indexed | 2024-04-13T16:47:01Z |
| format | Article |
| id | doaj.art-f859a5c89b094beab67a250bbc6e7abe |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-04-13T16:47:01Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of King Saud University: Science |
| spelling | doaj.art-f859a5c89b094beab67a250bbc6e7abe2022-12-22T02:39:03ZengElsevierJournal of King Saud University: Science1018-36472022-08-01346102165The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanismWahidah H. Al-Qahtani0Ghedeir M. Alshammari1Mohammad A. Alshuniaber2Mureed Husain3Sarah A. Alawwad4Salwa T. Al-Ayesh5Mohammed Abdo Yahya6Abdulrahman S. Aldawood7Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi ArabiaDepartment of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia; Corresponding author at: Riyadh, 11451, P.O. Box 2460, Saudi Arabia.Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi ArabiaEconomic Entomology Research Unit, Department of Plant Protection, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi ArabiaDepartment of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi ArabiaDepartment of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi ArabiaDepartment of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi ArabiaEconomic Entomology Research Unit, Department of Plant Protection, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi ArabiaObjectives: This study aimed to evaluate if the protective effect of Isoliquiritigenin (ISL) against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling. Methods: Adult male Wistart rats were treated as control, ISL, DOX, DOX, and ISL + DOX + ISL + Nrf2 inhibitor (brusatol) (n = 8/group). Treatments with ISL (25 mg//kg, oral) were carried out 10 days before and 10 days after the single dose of DOX (15 mg/kg, i.p). Results: Treatment with ISL attenuated the glomerular and tubular damage and reduced interstitial fibrosis and collagen accumulation in the kidneys of DOX-intoxicated animals. It also increased urinary flow and volume, stimulated urinary creatinine excretion, and decreased albumin excretion. These effects were associated with high transcription of Bcl2, suppression of ROS, MDA, and inflammatory cytokines production (i.e., TNF-α, IL-6, and IL-1β), downregulation of apoptotic markers (Bax and caspase-3/9), TGF-β1, Collagen I/III. Besides, ISL stimulated renal expression, translation, and nuclear localization of Nrf2, as well as levels of GSH and SOD, independent of keap-1. All these effects afforded by ISL were reversed by suppressing Nrf2 with brusatol. Conclusion: Pre-treatment with ISL is an effective strategy to alleviate DOX-induced nephropathy in rats by stimulating the Nrf2/antioxidant axis, which encourages further pre-clinical studies.http://www.sciencedirect.com/science/article/pii/S1018364722003469IsoliquiritigeninDoxorubicinNrf2AntioxidantKidney |
| spellingShingle | Wahidah H. Al-Qahtani Ghedeir M. Alshammari Mohammad A. Alshuniaber Mureed Husain Sarah A. Alawwad Salwa T. Al-Ayesh Mohammed Abdo Yahya Abdulrahman S. Aldawood The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanism Journal of King Saud University: Science Isoliquiritigenin Doxorubicin Nrf2 Antioxidant Kidney |
| title | The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanism |
| title_full | The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanism |
| title_fullStr | The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanism |
| title_full_unstemmed | The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanism |
| title_short | The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanism |
| title_sort | protective effect of isoliquiritigenin against doxorubicin induced nephropathy in rats entails activation of nrf2 signaling as one key mechanism |
| topic | Isoliquiritigenin Doxorubicin Nrf2 Antioxidant Kidney |
| url | http://www.sciencedirect.com/science/article/pii/S1018364722003469 |
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