The genotoxic effect of oxcarbazepine on mice blood lymphocytes

Abstract

This study was conducted to assess the amount of DNA damage caused by Oxcarbazepine (OXC) through single cell gel electrophoresis (SCGE) technique/comet assay. OXC derived from dibenzazepine series is an effective second generation antiepileptic drug (AED) for both children and adults. Side effects like genotoxic effects of AEDs are of prime importance resulting from toxic metabolites, free radicals and reactive oxygen species (ROS). Forty Eight adult male Bagg's albino mice (BALB/c) were randomly classified into eight groups, each comprising of six animals. Two of these groups were control and six were tested groups. Control groups were injected with 1% tween 80 while tested groups were injected with 10, 20, and 40 mg/kg-day OXC for seven days (acute therapy) and 28 days (subchronic therapy) in peritoneal cavity. Blood samples were collected by cardiac puncture and subjected to comet assay for the analysis of DNA damage. Per sample 100 cells were scored and classified according to comet tail length. The results showed that OXC in acute and long term therapies had significantly higher (p < 0.05) genotoxicity in treated groups as compared to control groups. Our study suggests that OXC may cause significant DNA damage in both acute as well as in subchronic therapies.

Antiepileptic Drug Teratogenicity and De Novo Genetic Variation Load

“…This hypothesis was based on 3 observations: (1) congenital malformations develop only in a minority of AED‐exposed fetuses 3,4 ; (2) there is considerable phenotypic overlap across congenital malformations associated with different AEDs, suggesting that AED‐associated birth defects possibly arise from dysregulation of a shared mechanism or pathway critical to fetal development; and (3) several teratogens, including drugs, have genotoxic or mutagenic effects . Although there is no conclusive evidence for AEDs being mutagenic, chromosomal/DNA damaging effects in vitro or in vivo have been reported for several AEDs, including VPA, phenytoin, barbiturates, carbamazepine, oxcarbazepine, and possibly lamotrigine . At least for VPA, the suggestion has been made that increased DNA damage may result from chronic inhibition of histone deacetylase .…”

Bio-monitoring of DNA damage in matchstick industry workers from Peshawar Khyber Pakhtunkhwa, Pakistan

“…Visual scoring is a reliable, simple, and rapid method for scoring the comets [18]. Total comet score (TCS) was then calculated according to the formula, TCS = 0(n) +1(n) +2(n) +3(n) +4(n), where "n" indicates number of cells in each class, thus the overall score for each slide was therefore between 0 (undamaged) and 400 (maximum damaged), as referred by Collins [18] and reported in our previous publications [19][20][21].…”