In vivo protective effect of 2-mercapto ethane sulfonic acid against sulfur mustard-induced inter-strand DNA crosslinks in rat bone marrow cells
Abstrakt
The protective efficacy of 2-mercapto ethane sulfonic acid (MESNA) against percutaneously administered sulfur mustard (SM) was evaluated in rats. MESNA was applied i.p. to female Wistar rats at doses 200, 400, or 800 mg/kg 30 minutes prior to the administration of sulfur mustard applied in three different doses (10, 20 or 40 mg/kg) to a coat-clipped skin area.
After different time intervals, the rats were sacrificed and the amount of inter-strand DNA crosslinks (ICLs) was estimated in peripheral lymphocytes, liver cells and bone marrow cells using a modified (inverse) comet assay. While no significant influence of MESNA was observed on the resulting inter-strand crosslinks in lymphocytes and liver cells, approximately a 25% reduction of inter-strand crosslinks induced by sulfur mustard was found in bone marrow cells of rats pre-treated with the highest dose of MESNA (800 mg/kg).
In contrast to MESNA, sodium thiosulfate, a recommended antidote against sulfur mustard applied at a dose of 1g/kg, did not have any effect on inter-strand crosslink induction. The present study suggests that MESNA might be an effective prophylactic agent against sulfur mustard toxicity.