Valproic acid monotherapy induces DNA oxidative damage

Area of Science:

• Biochemistry
• Pediatric Neurology
• Toxicology

Background:

• Valproic acid (VPA) is a common antiepileptic drug.
• VPA and oxidative stress markers like 8-hydroxy-2-deoxyguanosine (8-OHdG) are linked to free radical production.
• The impact of VPA monotherapy on oxidative status in children requires further investigation.

Purpose of the Study:

• To evaluate total oxidant status (TOS) and 8-OHdG levels in children receiving VPA monotherapy.
• To assess the relationship between VPA serum levels, oxidative stress, and DNA damage markers.

Main Methods:

• Fifty children with seizures on VPA monotherapy were divided into two groups based on VPA serum levels.
• Thirty healthy children served as controls.
• Liver function tests, lipid profiles, TOS, and 8-OHdG were measured after 60 days of VPA therapy.

Main Results:

• Children with higher VPA serum levels showed significantly elevated liver function parameters, lipids, TOS, and 8-OHdG compared to the lower VPA group and controls.
• A significant positive correlation was observed between 8-OHdG and TOS (r=0.67, p<0.001).
• A significant positive correlation was found between 8-OHdG and VPA serum levels (r=0.60, p<0.001).

Conclusions:

• VPA therapy in children may impair liver function, leading to increased free radical production and subsequent DNA oxidative damage.
• Elevated serum 8-OHdG levels in VPA-treated children suggest potential oxidative damage to liver and possibly neuronal cells.
• 8-OHdG may serve as a valuable biomarker for monitoring the risk of degenerative processes in children on VPA.