Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6 signals
5-Fluorouracil (5-FU) is one of the most used anticancer drugs. However, its nephrotoxicity-associated drawback is of clinical concern. Lycopene (LYC) is a red carotenoid with remarkable anti-inflammatory and anti-oxidative properties. In this study, rats were divided randomly into five groups: cont...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Renal Failure |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2423843 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850140145842388992 |
|---|---|
| author | Ghadeer M. Albadrani Ahmed E. Altyar Osama A. Kensara Mohie A.M Haridy Amany A. Sayed Zuhair M. Mohammedsaleh Muath Q. Al-Ghadi Rasha Mohammed Saleem Mohamed M. Abdel-Daim |
| author_facet | Ghadeer M. Albadrani Ahmed E. Altyar Osama A. Kensara Mohie A.M Haridy Amany A. Sayed Zuhair M. Mohammedsaleh Muath Q. Al-Ghadi Rasha Mohammed Saleem Mohamed M. Abdel-Daim |
| author_sort | Ghadeer M. Albadrani |
| collection | DOAJ |
| description | 5-Fluorouracil (5-FU) is one of the most used anticancer drugs. However, its nephrotoxicity-associated drawback is of clinical concern. Lycopene (LYC) is a red carotenoid with remarkable anti-inflammatory and anti-oxidative properties. In this study, rats were divided randomly into five groups: control, lycopene (10 mg) (10 mg/kg/day; P.O), 5-FU (30 mg/kg/day; i.p.), Lycopene (5 mg) + 5-FU (5 mg/kg + 30 mg/kg/day), and lycopene (10 mg) + 5-FU (10 mg/kg + 30 mg/kg/day). LYC attenuated the loss of renal function induced by 5-FU in a dose-dependent manner. Rats co-treated with LYC had lower serum urea, creatinine, uric acid and KIM-1 levels, and a higher serum albumin level than those receiving 5-FU alone. Furthermore, co-treatment with the high dose of LYC maintained renal oxidant–antioxidant balance by ameliorating/preventing the loss of antioxidants and the elevation of malondialdehyde. Rats treated with 5-FU had markedly lower renal levels of PPAR-gamma, HO-1, Nfr2, and Il-10 and higher levels of NF-kB, TNF-alpha, and IL6 compared to the control rats. Co-treatment with LYC attenuated the reduction in PPAR-gamma, HO-1, Nfr2, and IL-10 levels and moderated the elevated levels of NF-kB, TNF-alpha, and IL-6. The kidneys from rats co-treated with lycopene (10 mg) + 5-FU did not show the degenerative changes in the glomerular tufts and tubules observed for the rats treated with 5-FU alone. In conclusion, LYC is a promising therapeutic strategy for attenuating 5-FU-induced nephrotoxicity through the restoration of antioxidant activities and inhibition of inflammatory responses by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6, signals. |
| format | Article |
| id | doaj-art-d720a68a34cb470cbbe8b7cf6b26653f |
| institution | OA Journals |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-d720a68a34cb470cbbe8b7cf6b26653f2025-08-20T02:29:56ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2423843Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6 signalsGhadeer M. Albadrani0Ahmed E. Altyar1Osama A. Kensara2Mohie A.M Haridy3Amany A. Sayed4Zuhair M. Mohammedsaleh5Muath Q. Al-Ghadi6Rasha Mohammed Saleem7Mohamed M. Abdel-Daim8Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaDepartment of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Clinical Nutrition, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi ArabiaDepartment of Pathology and Laboratory Diagnosis, College of Veterinary Medicine, Qassim University, Buraidah, Saudi ArabiaZoology Department, Faculty of Science, Cairo University, Giza, EgyptDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi ArabiaDepartment of Zoology, College of Science, King Saud University, Riyadh, Saudi ArabiaDepartment of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi ArabiaDepartment of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia5-Fluorouracil (5-FU) is one of the most used anticancer drugs. However, its nephrotoxicity-associated drawback is of clinical concern. Lycopene (LYC) is a red carotenoid with remarkable anti-inflammatory and anti-oxidative properties. In this study, rats were divided randomly into five groups: control, lycopene (10 mg) (10 mg/kg/day; P.O), 5-FU (30 mg/kg/day; i.p.), Lycopene (5 mg) + 5-FU (5 mg/kg + 30 mg/kg/day), and lycopene (10 mg) + 5-FU (10 mg/kg + 30 mg/kg/day). LYC attenuated the loss of renal function induced by 5-FU in a dose-dependent manner. Rats co-treated with LYC had lower serum urea, creatinine, uric acid and KIM-1 levels, and a higher serum albumin level than those receiving 5-FU alone. Furthermore, co-treatment with the high dose of LYC maintained renal oxidant–antioxidant balance by ameliorating/preventing the loss of antioxidants and the elevation of malondialdehyde. Rats treated with 5-FU had markedly lower renal levels of PPAR-gamma, HO-1, Nfr2, and Il-10 and higher levels of NF-kB, TNF-alpha, and IL6 compared to the control rats. Co-treatment with LYC attenuated the reduction in PPAR-gamma, HO-1, Nfr2, and IL-10 levels and moderated the elevated levels of NF-kB, TNF-alpha, and IL-6. The kidneys from rats co-treated with lycopene (10 mg) + 5-FU did not show the degenerative changes in the glomerular tufts and tubules observed for the rats treated with 5-FU alone. In conclusion, LYC is a promising therapeutic strategy for attenuating 5-FU-induced nephrotoxicity through the restoration of antioxidant activities and inhibition of inflammatory responses by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6, signals.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2423843Lycopene5-fluorouracilnephrotoxicityPPAR-γNrf2/HO-1NF-κB |
| spellingShingle | Ghadeer M. Albadrani Ahmed E. Altyar Osama A. Kensara Mohie A.M Haridy Amany A. Sayed Zuhair M. Mohammedsaleh Muath Q. Al-Ghadi Rasha Mohammed Saleem Mohamed M. Abdel-Daim Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6 signals Renal Failure Lycopene 5-fluorouracil nephrotoxicity PPAR-γ Nrf2/HO-1 NF-κB |
| title | Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6 signals |
| title_full | Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6 signals |
| title_fullStr | Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6 signals |
| title_full_unstemmed | Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6 signals |
| title_short | Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6 signals |
| title_sort | lycopene alleviates 5 fluorouracil induced nephrotoxicity by modulating ppar γ nrf2 ho 1 and nf κb tnf α il 6 signals |
| topic | Lycopene 5-fluorouracil nephrotoxicity PPAR-γ Nrf2/HO-1 NF-κB |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2423843 |
| work_keys_str_mv | AT ghadeermalbadrani lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals AT ahmedealtyar lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals AT osamaakensara lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals AT mohieamharidy lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals AT amanyasayed lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals AT zuhairmmohammedsaleh lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals AT muathqalghadi lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals AT rashamohammedsaleem lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals AT mohamedmabdeldaim lycopenealleviates5fluorouracilinducednephrotoxicitybymodulatingppargnrf2ho1andnfkbtnfail6signals |