Naringenin mitigates 5-fluorouracil-induced nephrotoxicity by decreasing oxidative stress, inflammation and apoptosis

Area of Science:

• Pharmacology
• Toxicology
• Nephrology

Background:

• 5-fluorouracil (5-FU) is a widely used chemotherapy agent with known nephrotoxic effects.
• Drug-induced kidney damage is a significant clinical concern, necessitating protective strategies.
• Naringenin (NAR), a natural flavonoid, possesses antioxidant and anti-inflammatory properties.

Purpose of the Study:

• To investigate the protective effects of naringenin (NAR) against 5-fluorouracil (5-FU) induced nephrotoxicity.
• To elucidate the underlying mechanisms of NAR's renoprotective action.

Main Methods:

• Rats were divided into four groups: Control, NAR, 5-FU, and NAR + 5-FU.
• Kidney tissues and blood were analyzed using biochemical assays, immunohistochemistry, TUNEL assay, and histopathology.
• Key markers of oxidative stress, inflammation, apoptosis, and kidney function were assessed.

Main Results:

• 5-FU administration significantly increased MDA, BUN, TNF-α, caspase-3 levels, and apoptosis in kidney tissues.
• 5-FU induced severe histopathological damage, including inflammation, hemorrhage, and tubular injury.
• NAR treatment significantly attenuated 5-FU-induced oxidative stress, inflammation, apoptosis, and histopathological alterations.

Conclusions:

• Naringenin (NAR) effectively protects against 5-fluorouracil (5-FU) induced nephrotoxicity.
• NAR's protective effects are attributed to its antioxidant, anti-inflammatory, and anti-apoptotic properties.
• Therapeutic mechanisms involve Nrf2 upregulation and NF-κB downregulation.