Protective Effect of Natural Antioxidants on Reducing Cisplatin-Induced Nephrotoxicity

Area of Science:

• Biochemistry
• Toxicology
• Pharmacology

Background:

• Cisplatin is a vital chemotherapy drug, but its use is limited by severe nephrotoxicity.
• Oxidative stress, driven by reactive oxygen species (ROS), is a key mechanism in cisplatin-induced kidney damage.
• ROS trigger cellular damage pathways like apoptosis and necrosis, contributing to organ dysfunction.

Purpose of the Study:

• To review the mechanisms of intracellular ROS generation by cisplatin.
• To explore how natural antioxidants counteract cisplatin-induced nephrotoxicity.
• To provide a foundation for understanding cisplatin nephrotoxicity and the role of antioxidants.

Main Methods:

• Literature review focusing on cisplatin's effects on cellular redox balance.
• Analysis of studies investigating ROS generation pathways (antioxidant depletion, enzyme/CYP system damage, mitochondrial crosstalk).
• Examination of research on natural antioxidant interventions against cisplatin nephrotoxicity.

Main Results:

• Cisplatin induces ROS accumulation via endogenous antioxidant depletion, antioxidant enzyme destruction, and endoplasmic reticulum-mitochondria crosstalk.
• Mitochondrial crosstalk involving ROS and Ca2+ exacerbates cellular damage.
• The cytochrome P450 system's destruction in the endoplasmic reticulum contributes to oxidative stress.
• Natural antioxidants effectively mitigate cisplatin-induced nephrotoxicity by scavenging ROS and influencing non-redox pathways.

Conclusions:

• Understanding cisplatin-induced ROS generation is crucial for managing nephrotoxicity.
• Natural antioxidants offer a promising therapeutic strategy to protect against cisplatin-induced kidney damage.
• This review supports further research into natural antioxidants for clinical applications alongside cisplatin therapy.