Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigations
Abstract Background Drugs, chemicals, and poisons may damage kidneys and cause chronic renal disease. About 20% of community and hospital acute renal failures are drug-related. Objectives Hesperidin-loaded bilosomes (HES-BS) nanoformula was tested for nephroprotection against methotrexate (MTX)-indu...
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2025-07-01
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| Series: | BMC Nephrology |
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| Online Access: | https://doi.org/10.1186/s12882-025-04328-4 |
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| author | Shiemaa H. Mahmoud Walaa A. Moselhy Ahmed F. Azmy Fatma I. Abo El-Ela |
| author_facet | Shiemaa H. Mahmoud Walaa A. Moselhy Ahmed F. Azmy Fatma I. Abo El-Ela |
| author_sort | Shiemaa H. Mahmoud |
| collection | DOAJ |
| description | Abstract Background Drugs, chemicals, and poisons may damage kidneys and cause chronic renal disease. About 20% of community and hospital acute renal failures are drug-related. Objectives Hesperidin-loaded bilosomes (HES-BS) nanoformula was tested for nephroprotection against methotrexate (MTX)-induced kidney injury in rats. Thin-film hydration produced HES-BS nanoformula. Drug-loading capacity, encapsulation efficiency (EE %), FTIR, DSC, zeta sizer, and potential were employed for characterization, coupled with an in vitro release study. In vivo pharmacological investigations on White male albino rats measured metabolic parameters, oxidative stress indicators, Nrf2 /Keap1 and BCL2/Bax gene expression, and histopathological alterations. Results The HES-BS nanoformula was synthesized with 162 nm particles and − 21.6 mv potential charge. The Transmissions electron microscopy (TEM) showed spherical HES-BS. Hesperidin-excipient compatibility was shown by FTIR and DSC investigations on the modified formulation, with 89.1% EE%. In vitro drug release showed 56% release after eight hours and 60.1% after 24 h, with greater bioavailability than crude HES. The IC₅₀ value of hesperidin decreased from 264 µg/mL to 106.2 µg/mL upon bilosome loading in Vero cells. MTX’s nephrotoxicity was mitigated by the HES-BS nano formula’s effects on creatinine, urea, uric acid, eGFR, Na, and K levels. Malondialdehyde (MDA) and Nitric Oxide (NO) were notably decreased, whereas Glutathione (GSH) and Superoxide Dismutase (SOD) were markedly elevated. Also, Nrf2 and Bcl2 were upregulated, while Keap1 and Bax were downregulated. Additionally, the produced nanoformula improved the histopathological function. Conclusion Our novel HES-BS nanoformula had potent nephroprotective activity by reducing the toxic effects of MTX treatment by improving biochemical indicators of kidney function, oxidative stress markers, anti-apoptotic gene expression, and apoptotic gene expression, as well as histopathological improvement. |
| format | Article |
| id | doaj-art-1e0eb0b01ff247b4b9c95ae3fe7c33ac |
| institution | Kabale University |
| issn | 1471-2369 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj-art-1e0eb0b01ff247b4b9c95ae3fe7c33ac2025-08-20T04:01:53ZengBMCBMC Nephrology1471-23692025-07-0126111610.1186/s12882-025-04328-4Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigationsShiemaa H. Mahmoud0Walaa A. Moselhy1Ahmed F. Azmy2Fatma I. Abo El-Ela3Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef UniversityDepartment of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Beni-Suef UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Beni- Suef UniversityPharmacology Department, Faculty of Veterinary Medicine, Beni-Suef UniversityAbstract Background Drugs, chemicals, and poisons may damage kidneys and cause chronic renal disease. About 20% of community and hospital acute renal failures are drug-related. Objectives Hesperidin-loaded bilosomes (HES-BS) nanoformula was tested for nephroprotection against methotrexate (MTX)-induced kidney injury in rats. Thin-film hydration produced HES-BS nanoformula. Drug-loading capacity, encapsulation efficiency (EE %), FTIR, DSC, zeta sizer, and potential were employed for characterization, coupled with an in vitro release study. In vivo pharmacological investigations on White male albino rats measured metabolic parameters, oxidative stress indicators, Nrf2 /Keap1 and BCL2/Bax gene expression, and histopathological alterations. Results The HES-BS nanoformula was synthesized with 162 nm particles and − 21.6 mv potential charge. The Transmissions electron microscopy (TEM) showed spherical HES-BS. Hesperidin-excipient compatibility was shown by FTIR and DSC investigations on the modified formulation, with 89.1% EE%. In vitro drug release showed 56% release after eight hours and 60.1% after 24 h, with greater bioavailability than crude HES. The IC₅₀ value of hesperidin decreased from 264 µg/mL to 106.2 µg/mL upon bilosome loading in Vero cells. MTX’s nephrotoxicity was mitigated by the HES-BS nano formula’s effects on creatinine, urea, uric acid, eGFR, Na, and K levels. Malondialdehyde (MDA) and Nitric Oxide (NO) were notably decreased, whereas Glutathione (GSH) and Superoxide Dismutase (SOD) were markedly elevated. Also, Nrf2 and Bcl2 were upregulated, while Keap1 and Bax were downregulated. Additionally, the produced nanoformula improved the histopathological function. Conclusion Our novel HES-BS nanoformula had potent nephroprotective activity by reducing the toxic effects of MTX treatment by improving biochemical indicators of kidney function, oxidative stress markers, anti-apoptotic gene expression, and apoptotic gene expression, as well as histopathological improvement.https://doi.org/10.1186/s12882-025-04328-4HesperidinBilosomesNephrotoxicityNrf2Keap1Bcl2 |
| spellingShingle | Shiemaa H. Mahmoud Walaa A. Moselhy Ahmed F. Azmy Fatma I. Abo El-Ela Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigations BMC Nephrology Hesperidin Bilosomes Nephrotoxicity Nrf2 Keap1 Bcl2 |
| title | Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigations |
| title_full | Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigations |
| title_fullStr | Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigations |
| title_full_unstemmed | Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigations |
| title_short | Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigations |
| title_sort | hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate biochemical and molecular in vivo investigations |
| topic | Hesperidin Bilosomes Nephrotoxicity Nrf2 Keap1 Bcl2 |
| url | https://doi.org/10.1186/s12882-025-04328-4 |
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