Protective Role of Boldine Against 5-Fluorouracil-Induced Nephrotoxicity: In Vitro and In Vivo Approach

Area of Science:

• Pharmacology
• Toxicology
• Nephrology

Background:

• Drug-induced nephrotoxicity is a critical issue in chemotherapy, with 5-fluorouracil (5-FU) being a notable culprit.
• Identifying protective agents against chemotherapy-induced kidney damage is crucial for patient safety and treatment efficacy.

Purpose of the Study:

• To evaluate the nephroprotective potential of boldine, an aporphine alkaloid, against 5-FU-induced renal toxicity.
• To elucidate the underlying mechanisms of boldine's protective effects in both in vitro and in vivo models.

Main Methods:

• In vitro studies used HEK293 cells to assess cytotoxicity (MTT assay) and apoptosis (AO/EB, DAPI staining).
• In vivo studies involved Wistar rats treated with 5-FU and subsequently with boldine or silymarin, analyzing serum biochemical markers, kidney oxidative stress indicators, gene expression (MAPK pathway), and histopathology.

Main Results:

• Boldine treatment restored cell viability and morphology in 5-FU-treated HEK cells, reducing apoptosis.
• In vivo, boldine normalized elevated nephrotoxic markers, enhanced antioxidant enzyme activity, and inhibited pro-inflammatory signaling pathways (ASK1, ERK1, c-Jun, NF-κB1).
• Histopathological analysis confirmed that boldine preserved renal tissue integrity, preventing tubular and glomerular damage.

Conclusions:

• Boldine exhibits significant nephroprotective properties against 5-FU-induced renal injury.
• The protective mechanisms involve anti-apoptotic, antioxidant, and anti-inflammatory effects, highlighting boldine as a potential therapeutic agent for mitigating chemotherapy-induced nephrotoxicity.