Related Experiment Video
Updated: Nov 12, 2025
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Targeting KEAP1/Nrf2, AKT, and PPAR-γ signals as a potential protective mechanism of diosmin against
Fares E M Ali1, Ahmed M Sayed2, Ali H El-Bahrawy1
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt.
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-γ) 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-γ proteins.
Significance:
DS could be a promising protective agent against GM-induced nephrotoxicity through targeting of KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways.
Insights
Diosmin (DS) protects against gentamicin (GM)-induced kidney damage by restoring antioxidant balance and targeting key signaling pathways. This study highlights DS as a potential therapeutic agent for preventing nephrotoxicity.
Area of Science:
- Pharmacology and Toxicology
- Biochemistry
- Nephrology
Background:
- Gentamicin (GM) is a vital antibiotic for severe infections but causes nephrotoxicity, limiting its use.
- Diosmin (DS), a flavonoid, has diverse bioactivities, but its protective effects against GM-induced kidney damage are not well understood.
Purpose of the Study:
- To investigate the potential protective effects of Diosmin (DS) against Gentamicin (GM)-induced nephrotoxicity in a rat model.
- To elucidate the underlying molecular mechanisms involving key signaling pathways.
Main Methods:
- Rats were treated with GM (100 mg/kg) for 7 days, with or without co-administration of DS (50 mg/kg).
- Kidney function, oxidant/antioxidant status, and expressions of Nrf2, GCLC, HO-1, SOD-3, AKT, KEAP1, and PPAR-γ were assessed.
- In-silico analysis was performed to confirm binding affinities of DS to target proteins.
Main Results:
- GM induced kidney dysfunction, oxidative stress, and altered expressions of Nrf2, AKT, and PPAR-γ signaling molecules.
- DS treatment significantly attenuated GM-induced nephrotoxicity, restored oxidant/antioxidant balance, and modulated the expression of key proteins.
- In-silico studies supported the biochemical findings, showing binding affinity of DS to KEAP1, AKT, and PPAR-γ.
Conclusions:
- Diosmin (DS) demonstrates significant protective effects against Gentamicin (GM)-induced nephrotoxicity.
- DS acts by targeting the KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways.
- DS is a promising therapeutic candidate for preventing GM-induced kidney damage.
More Related Videos
14:18Author Spotlight: Investigating the Potential of Chinese Herbal Medicinal Active Dioscin in Treating IgA Nephropathy
Published on: October 13, 2023
08:15Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
Related Concept Videos
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include: