Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and...

Area of Science:

• Pharmacology and Toxicology
• Nephrology
• Molecular Biology

Background:

• Gentamicin (GNT), a widely used aminoglycoside antibiotic, is associated with significant nephrotoxicity, limiting its clinical application.
• Understanding the molecular mechanisms underlying GNT-induced kidney damage is crucial for developing effective protective strategies.
• Diosmin (DIOS), a flavonoid, has shown potential therapeutic benefits, but its protective effects against GNT nephrotoxicity require detailed investigation.

Purpose of the Study:

• To evaluate the renoprotective potential of Diosmin (DIOS) against Gentamicin (GNT)-induced kidney injury in a rat model.
• To elucidate the underlying molecular pathways, including microRNA (miR-21, miR-155) expression and the Nrf2/HO-1 and p38-MAPK/NF-κB signaling cascades, involved in DIOS's nephroprotective action.

Main Methods:

• Rats were divided into four groups: control, GNT only, GNT + DIOS, and DIOS only.
• Assessment of kidney function markers (serum urea, creatinine, KIM-1), oxidative stress (MDA, TAC, SOD), and inflammatory cytokines (TNF-α, IL-1β).
• Evaluation of key protein expressions (Nrf2, HO-1, p38-MAPK, NF-κB p65, caspase-3, BAX, Bcl-2), microRNA levels (miR-21, miR-155), and histological kidney damage.

Main Results:

• GNT administration significantly increased kidney weight, serum markers of renal damage, oxidative stress, and inflammation, while decreasing antioxidant enzyme levels.
• GNT induced apoptosis (elevated caspase-3, BAX; reduced Bcl-2), altered miR-21 (down-regulation) and miR-155 (up-regulation) expression, and activated p38-MAPK/NF-κB pathways.
• DIOS treatment markedly reversed GNT-induced nephrotoxicity, restoring normal kidney histology, biochemical parameters, and modulating the investigated molecular pathways.

Conclusions:

• Diosmin (DIOS) exhibits significant renoprotective effects against Gentamicin (GNT)-induced nephrotoxicity in rats.
• The protective mechanisms of DIOS involve the regulation of oxidative stress, inflammation, apoptosis, and modulation of miR-21, miR-155, Nrf2/HO-1, and p38-MAPK/NF-κB signaling pathways.
• DIOS represents a promising therapeutic agent for preventing or treating GNT-induced kidney damage.