Mitochondrial oxidative stress-induced brain and hippocampus apoptosis decrease through modulation of caspase...

Area of Science:

• Neuroscience
• Toxicology
• Biochemistry

Background:

• Docetaxel (DOCE) is a chemotherapy drug with known toxicities that limit its use.
• The neurotoxic effects of DOCE on the brain cortex and hippocampus are not well understood.
• Melatonin (MLT) and selenium (SELEN) have shown protective effects against DOCE-induced toxicity in other tissues.

Purpose of the Study:

• To investigate the protective effects of MLT and SELEN against DOCE-induced oxidative toxicity in the brain and hippocampus of mice.
• To elucidate the mechanisms underlying the neuroprotective actions of MLT and SELEN.

Main Methods:

• Mice were pretreated with MLT and SELEN before DOCE administration.
• Mitochondrial reactive oxygen species (ROS), lipid peroxidation, and antioxidant status were measured.
• Cell viability, TRPM2 channel activation, and inflammatory markers (TNF-α, IL-1β, IL-6) were assessed.
• Apoptosis-related proteins (caspase-3, caspase-9) were analyzed.

Main Results:

• MLT and SELEN pretreatments significantly reduced DOCE-induced mitochondrial ROS production, lipid peroxidation, and mitochondrial membrane depolarization in brain and hippocampus tissues.
• Antioxidant markers, including glutathione, glutathione peroxidase, and various vitamins, were increased by MLT and SELEN.
• Cell viability was enhanced, while inflammatory responses and apoptosis signaling pathways (caspase-3, caspase-9) were suppressed.
• SELEN demonstrated a more significant modulatory role than MLT.

Conclusions:

• MLT and SELEN effectively prevent DOCE-induced brain and hippocampus injury by inhibiting mitochondrial ROS and cellular apoptosis.
• These protective effects are mediated through the regulation of caspase-3 and caspase-9 activation signaling pathways.
• MLT and SELEN represent promising therapeutic agents for mitigating DOCE-induced neurotoxicity in the hippocampus and brain.