ReferenceID 1787
Targeting KEAP1/Nrf2, AKT, and PPAR-γ signals as a potential protective mechanism of diosmin against gentamicin-induced nephrotoxicity
Life Sci
AIM: Gentamicin (GM) is an aminoglycoside antibiotic effectively used for severe/life-threatening infections. However, the clinical application of GM is limited by nephrotoxic side effects. Diosmin (DS) is a flavonoid wi
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 1787
- Evidence Id
- 18377
- Core Evidence Id
- 18377
- Source Reference Id
- 3565
- Herb2 Reference Id
- HBREF004362
- Subject Paper Key
- HBIN024193_33744325
- Pubmed Id
- 33744325
- Doi
- 10.1016/j.lfs.2021.119349
- Paper Title
- Targeting KEAP1/Nrf2, AKT, and PPAR-γ signals as a potential protective mechanism of diosmin against gentamicin-induced nephrotoxicity
- Paper Abstract
- AIM: Gentamicin (GM) is an aminoglycoside antibiotic effectively used for severe/life-threatening infections. However, the clinical application of GM is limited by nephrotoxic side effects. Diosmin (DS) is a flavonoid with a wide range of bioactivities. However, its therapeutic potential in GM-induced nephrotoxicity remains unclear. METHODS: Rats received GM (100 mg/kg, i.p.) for 7 days either separately or in combination with oral DS (50 mg/kg). RESULTS: GM injection disrupted kidney function along with oxidant/antioxidant imbalance. Also, GM significantly decreased renal nuclear factor erythroid 2-related factor 2 (Nrf2), glutamyl cysteine synthetase (GCLC), heme oxygenase-1 (HO-1), superoxide dismutase3 (SOD-3), protein kinase B (AKT), and p-AKT expressions along with Kelch-like ECH-associated protein 1 (KEAP1) up-regulation. On the contrary, DS administration significantly attenuated GM-induced kidney dysfunction and restored kidney oxidant/antioxidant status. In addition, co-treatment with DS plus GM significantly enhanced Nrf2, GCLC, HO-1, SOD3, AKT, and p-AKT expressions along with KEAP1 down-regulation. Additionally, GM-treated rats exhibited a significant decrease in the expressions of renal peroxisome-proliferator activated receptor-gamma (PPAR-gamma) and this reduction was alleviated by DS treatment. Furthermore, histopathological findings demonstrated that DS significantly reduced the GM-induced histological abrasions. Besides, an in-silico study was conducted to confirm our biochemical results. Interestingly, in-silico results strongly supported our biochemical investigation by studying the binding affinity of DS to KEAP1, AKT, and PPAR-gamma proteins. SIGNIFICANCE: DS could be a promising protective agent against GM-induced nephrotoxicity through targeting of KEAP1/Nrf2/ARE, AKT, and PPAR-gamma signaling pathways.
- Journal
- Life Sci
- Publish Year
- 2021
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Kidney Dysfunction; Gm-induced Nephrotoxicity
- Paper Title Cn
- Paper Title En
- Targeting KEAP1/Nrf2, AKT, and PPAR-γ signals as a potential protective mechanism of diosmin against gentamicin-induced nephrotoxicity
- Bilingual Status
- semi_complete