Comparative toxic effect of nitrogen mustards (HN-1, HN-2, and HN-3) and sulfur mustard on hematological and biochemical variables and their protection by DRDE-07 and its analogues.
The chemical warfare agents sulfur mustard (SM) and nitrogen mustards (HN-1, HN-2, and HN-3) are highly reactive vesicants. The study was planned to investigate the protective efficacy of amifostine, DRDE-07 and their analogues, and few conventional antidotes (30 minutes pretreatment) against dermally applied SM and nitrogen mustards in preventing hematological and biochemical changes in mice. Mustard agents (1.0 median lethal dose [LD(50)]) induced a significant decrease in the body weight and spleen weight. A significant decrease in the white blood cell (WBC) count and an increase in serum transaminases and alkaline phosphatases (ALPs) were observed. A significant decrease in reduced (GSH) and oxidized glutathione (GSSG) and an increase in thiobarbituric acid reactive substances were also observed. All the mustard agents increased DNA fragmentation. The effects of SM were significantly ameliorated by DRDE-07 analogues, and with nitrogen mustards the protection was partial. Overall, DRDE-30 (propyl analogue) followed by DRDE-35 (butyl analogue) are favored as safer and better compounds.
Sharma
Manoj
M
Defence Research and Development Establishment, Gwalior 474002, India.
Vijayaraghavan
R
R
Agrawal
Om Prakash
OP
D000469:Alkaline Phosphatase / Q000097:blood*; D004999:Amifostine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D007928:Lethal Dose 50; D007958:Leukocyte Count; D008466:Mechlorethamine / Q000633:toxicity*; D051379:Mice; D009151:Mustard Gas / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000637:Transaminases / Q000097:blood*
C438646:S-2 (2-aminoethylamino)ethylphenylsulfide; D017392:Thiobarbituric Acid Reactive Substances; D008466:Mechlorethamine; D000637:Transaminases; D000469:Alkaline Phosphatase; D004999:Amifostine; D009151:Mustard Gas