Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect
Abstract Background The pathophysiology and severity of kidney impairment due to doxorubicin (DOX) treatment are markedly influenced by oxidative stress and inflammation. Naringin (NG), a natural flavonoid, has anti-inflammatory and antioxidant properties. The nephroprotective effect of NG on DOX-in...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | BMC Pharmacology and Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40360-025-00947-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849420427958419456 |
|---|---|
| author | Nahla S. Gad Sameh M. Shabana Maggie E. Amer Azza I. Othman Mohamed A. El-Missiry |
| author_facet | Nahla S. Gad Sameh M. Shabana Maggie E. Amer Azza I. Othman Mohamed A. El-Missiry |
| author_sort | Nahla S. Gad |
| collection | DOAJ |
| description | Abstract Background The pathophysiology and severity of kidney impairment due to doxorubicin (DOX) treatment are markedly influenced by oxidative stress and inflammation. Naringin (NG), a natural flavonoid, has anti-inflammatory and antioxidant properties. The nephroprotective effect of NG on DOX-induced kidney toxicity was investigated to increase its utility in clinical settings. Methods DOX toxicity was induced by a single ip injection (15 mg/kg) and for possible protection NG (100 mg/Kg) was used. Results Kidney damage and dysfunction were indicated by an elevation in the levels of creatinine, urea, uric acid, and the activity of ALP and LDH in serum, KIM-1, and NAGAL in kidney, and a significant decrease in nephrin and podocin in renal tissue. These disrupted glomerular and tubular function indicators were remarkably ameliorated by oral administration of NG (100 mg/kg) daily for 10 days before DOX treatment and continued for an additional four days post-Dox treatment. The nephroprotective effect of NG was confirmed by the improvement of histopathological and PAS histochemical investigations. The mitigating impact of NG was verified by normalization of the redox balance, evidenced by a significant amelioration of ROS levels, oxidative stress markers (MDA, PC, 8-OHdG), and antioxidants (GSH, GPx, GR), as well as upregulation of Nrf2 expression in kidney. Furthermore, NG significantly prevented the increase in the inflammatory mediators (IL-6, IL-1β, TNF-α, and NF-κB) and upregulated the anti-inflammatory IL-10 in DOX-treated rats. The expression of TGF-β1 and the apoptotic protein caspase-3 in the kidneys significantly decreased as a result of the improvement in redox state in renal tissue. Additionally, NG demonstrated anticancer effects and their combination showed synergistic anticancer impact on larynx and colon cancer cell lines in vitro study. Conclusions NG demonstrated remarkable protection of kidney against DOX treatment. |
| format | Article |
| id | doaj-art-3e48eb048b464310894bee14246455ce |
| institution | Kabale University |
| issn | 2050-6511 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pharmacology and Toxicology |
| spelling | doaj-art-3e48eb048b464310894bee14246455ce2025-08-20T03:31:45ZengBMCBMC Pharmacology and Toxicology2050-65112025-06-0126111510.1186/s40360-025-00947-7Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effectNahla S. Gad0Sameh M. Shabana1Maggie E. Amer2Azza I. Othman3Mohamed A. El-Missiry4Zoology Department, Faculty of Science, Mansoura UniversityZoology Department, Faculty of Science, Mansoura UniversityZoology Department, Faculty of Science, Mansoura UniversityZoology Department, Faculty of Science, Mansoura UniversityZoology Department, Faculty of Science, Mansoura UniversityAbstract Background The pathophysiology and severity of kidney impairment due to doxorubicin (DOX) treatment are markedly influenced by oxidative stress and inflammation. Naringin (NG), a natural flavonoid, has anti-inflammatory and antioxidant properties. The nephroprotective effect of NG on DOX-induced kidney toxicity was investigated to increase its utility in clinical settings. Methods DOX toxicity was induced by a single ip injection (15 mg/kg) and for possible protection NG (100 mg/Kg) was used. Results Kidney damage and dysfunction were indicated by an elevation in the levels of creatinine, urea, uric acid, and the activity of ALP and LDH in serum, KIM-1, and NAGAL in kidney, and a significant decrease in nephrin and podocin in renal tissue. These disrupted glomerular and tubular function indicators were remarkably ameliorated by oral administration of NG (100 mg/kg) daily for 10 days before DOX treatment and continued for an additional four days post-Dox treatment. The nephroprotective effect of NG was confirmed by the improvement of histopathological and PAS histochemical investigations. The mitigating impact of NG was verified by normalization of the redox balance, evidenced by a significant amelioration of ROS levels, oxidative stress markers (MDA, PC, 8-OHdG), and antioxidants (GSH, GPx, GR), as well as upregulation of Nrf2 expression in kidney. Furthermore, NG significantly prevented the increase in the inflammatory mediators (IL-6, IL-1β, TNF-α, and NF-κB) and upregulated the anti-inflammatory IL-10 in DOX-treated rats. The expression of TGF-β1 and the apoptotic protein caspase-3 in the kidneys significantly decreased as a result of the improvement in redox state in renal tissue. Additionally, NG demonstrated anticancer effects and their combination showed synergistic anticancer impact on larynx and colon cancer cell lines in vitro study. Conclusions NG demonstrated remarkable protection of kidney against DOX treatment.https://doi.org/10.1186/s40360-025-00947-7NaringinDoxorubicinKidney injuryAntioxidantsInflammationKidney histopathology |
| spellingShingle | Nahla S. Gad Sameh M. Shabana Maggie E. Amer Azza I. Othman Mohamed A. El-Missiry Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect BMC Pharmacology and Toxicology Naringin Doxorubicin Kidney injury Antioxidants Inflammation Kidney histopathology |
| title | Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect |
| title_full | Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect |
| title_fullStr | Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect |
| title_full_unstemmed | Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect |
| title_short | Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect |
| title_sort | naringin mitigated doxorubicin induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect |
| topic | Naringin Doxorubicin Kidney injury Antioxidants Inflammation Kidney histopathology |
| url | https://doi.org/10.1186/s40360-025-00947-7 |
| work_keys_str_mv | AT nahlasgad naringinmitigateddoxorubicininducedkidneyinjurybythereductionofoxidativestressandinflammationwithasynergisticanticancereffect AT samehmshabana naringinmitigateddoxorubicininducedkidneyinjurybythereductionofoxidativestressandinflammationwithasynergisticanticancereffect AT maggieeamer naringinmitigateddoxorubicininducedkidneyinjurybythereductionofoxidativestressandinflammationwithasynergisticanticancereffect AT azzaiothman naringinmitigateddoxorubicininducedkidneyinjurybythereductionofoxidativestressandinflammationwithasynergisticanticancereffect AT mohamedaelmissiry naringinmitigateddoxorubicininducedkidneyinjurybythereductionofoxidativestressandinflammationwithasynergisticanticancereffect |