Lycopene alleviates 5-fluorouracil-induced nephrotoxicity by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6...

Area of Science:

• Nephrology
• Pharmacology
• Biochemistry

Background:

• 5-Fluorouracil (5-FU) is a widely used chemotherapy agent with significant nephrotoxicity.
• Lycopene (LYC), a potent antioxidant and anti-inflammatory carotenoid, has potential renoprotective properties.

Purpose of the Study:

• To investigate the protective effects of Lycopene against 5-Fluorouracil-induced nephrotoxicity in a rat model.
• To elucidate the underlying mechanisms involving oxidative stress and inflammatory pathways.

Main Methods:

• Rats were administered 5-Fluorouracil (30 mg/kg) with or without varying doses of Lycopene (5 or 10 mg/kg).
• Renal function markers (serum urea, creatinine, albumin), oxidative stress markers (antioxidants, MDA), and inflammatory markers (PPAR-γ, HO-1, Nrf2, IL-10, NF-κB, TNF-α, IL-6) were assessed.
• Renal histopathology was examined.

Main Results:

• Lycopene attenuated 5-FU-induced renal dysfunction, evidenced by improved serum markers and reduced kidney injury molecule-1 (KIM-1).
• LYC treatment dose-dependently restored oxidant-antioxidant balance and reduced lipid peroxidation.
• Co-administration of LYC modulated key signaling pathways, decreasing pro-inflammatory markers (NF-κB, TNF-α, IL-6) and increasing anti-inflammatory and antioxidant markers (PPAR-γ, Nrf2/HO-1, IL-10).
• Histological examination revealed reduced kidney damage in rats treated with LYC and 5-FU compared to 5-FU alone.

Conclusions:

• Lycopene demonstrates significant renoprotective effects against 5-FU-induced nephrotoxicity.
• The protective mechanisms involve the restoration of antioxidant capacity and the suppression of inflammatory responses.
• Lycopene represents a promising therapeutic strategy to mitigate the kidney toxicity associated with 5-FU chemotherapy.