Abstract

HISTOPATHOLOGICAL EVALUATION OF VITAL ORGANS OF MICE EXPOSED TO MUSTARD AGENTS AND ITS PROTECTION BY VARIOUS ANTIDOTES

Sharma Manoj*, Pant SC and Vijayaraghavan R

ABSTRACT

The present study describes comparative protective efficacy of amifostine, DRDE-07, its analogues and other recommended antidotes against 1.0 LD50 dose of highly reactive blister inducing nitrogen mustards(HN-1, HN-2, HN-3) and sulphur mustard (SM) on some visceral organs of mice. The antidotes were administered orally, with first dose given at 30 min before the dermal exposure of 1.0 LD50 dose of HN-1, HN-2, HN-3 and SM (HN-1= 11.9 mg/kg; HN-2= 20.0 mg/kg; HN-3= 7.1 mg/kg and SM=8.1 mg/kg) while remaining doses on the next 3 to 7 successive days (a total dose of 4 or 8 doses). For DRDE-07, 0.2 LD50 (249 mg/kg) was used and for other analogues, equimolar dose of DRDE-07 was used. For amifostine, N-acetyl cysteine, melatonin and sodium thiosulphate, 185, 250, 250 and 1000 mg/kg respectively was used. Histological examination of spleen and liver of mice exposed to nitrogen and sulphur mustard revealed significant lesions. These lesions are evidenced by granulovacuolar degeneration and perinuclear clumping of cytoplasm in hepatocytes. Spelenic lesions were congestion and hypocellularity of white pulp, indicative of oxidative stress. It was concluded that both nitrogen and sulphur mustard are highly toxic by percutaneous route of administration. Lesions caused by nitrogen mustard and sulphur mustard were partially protect and also blocked their further progression by treatment with DRDE-07 and its analogues.

Keywords: Nitrogen mustard, Cytotoxicity, Antidote, Amifostine, DRDE-07 analogues.