Celastrol Mitigates Colistin-Induced Renal Toxicity in Rats via Modulating Nrf-2/HO-1 and NF-κB Signaling Pathways

Area of Science:

• Pharmacology
• Nephrology
• Toxicology

Background:

• Colistin (CST) is a vital antibiotic for treating multidrug-resistant bacterial infections but causes significant nephrotoxicity.
• Celastrol (CELA), a triterpenoid from Tripterygium wilfordii, possesses antioxidant, anti-inflammatory, and antiapoptotic properties.

Purpose of the Study:

• To evaluate the potential nephroprotective efficacy of Celastrol against Colistin-induced kidney damage.

Main Methods:

• Rats were administered Colistin alone or in combination with Celastrol (0.5 or 1 mg/kg).
• Kidney tissues were analyzed using histological staining (H&E, Masson's trichrome, Picrosirius Red, PAS).
• Serum markers, oxidative stress indicators, inflammatory markers, and apoptosis-related proteins were assessed.

Main Results:

• Colistin treatment induced severe renal histopathological damage, fibrosis, elevated serum urea, creatinine, and cystatin C.
• CST-induced nephrotoxicity involved increased oxidative stress, inflammation (COX-2, iNOS, TNF-α, NF-κB), and apoptosis (Bax, CASP3).
• Celastrol pretreatment significantly ameliorated these histopathological, biochemical, and molecular changes.

Conclusions:

• Celastrol exhibits significant protective effects against Colistin-induced nephrotoxicity in a rat model.
• CELA mitigates kidney injury by reducing oxidative stress, inflammation, and apoptosis.