Ameliorative effect of DRDE 07 and its analogues on the systemic toxicity of sulphur mustard and nitrogen mustard in rabbit.
Despite extensive research efforts, there is no unanimous approval of any animal model to evaluate the toxicity of sulphur mustard [SM; bis (2-chloroethyl) sulphide] or nitrogen mustard [HN-3; tris-(2-chloroethyl) amine] and screening of various prophylactic and therapeutic agents against them. In this study, differential toxicity of mustard agents in higher animal model that is male rabbit was determined. Protective efficacy of DRDE 07 [S-2(2-aminoethylamino) ethyl phenyl sulphide] and its analogues were also evaluated against SM and HN-3 toxicity. Differential toxicity study of SM and HN-3 reveals that both the compounds were more toxic by percutaneous route as compared to subcutaneous route. Till date, there is no recommended drug to counteract SM induced toxicity or mortality in vivo. However, DRDE 07 (an amifostine analogue) and its analogues are found to be very effective protective agents against percutaneously exposed SM in rabbits. The present experiments also showed that SM does not cause skin injury alone but also can cause systemic toxicity as well. DRDE 07 and many of its analogues may prove as prototype compounds for the development of better prophylactic and therapeutic drugs to counter the toxicity of SM or HN-3. In conclusion, rodents and rabbits can be used for the screening of drugs against the blistering agents.
Kumar
Pravin
P
Defence Research and Development Establishment, Gwalior, India.
Gautam
Anshoo
A
Prakash
Chandra Jatav
CJ
Kumar
Abdhesh
A
Ganeshan
K
K
Pathak
Uma
U
Vijayaraghavan
R
R
D000279:Administration, Cutaneous; D004999:Amifostine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008297:Male; D009151:Mustard Gas / Q000008:administration & dosage / Q000633:toxicity*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D013997:Time Factors
D000931:Antidotes; D002619:Chemical Warfare Agents; D009588:Nitrogen Mustard Compounds; D020011:Protective Agents; C438646:S-2 (2-aminoethylamino)ethylphenylsulfide; C009802:2,2',2''-trichlorotriethylamine; D004999:Amifostine; D009151:Mustard Gas