Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity.

Abstract

Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and several other macromolecules, and induces oxidative stress. Although several antidotes have been screened for the treatment of systemic toxicity of SM in experimental animals none of them are recommended so far. In the search for more effective and less toxic antidotes, various combinations were tried against SM induced toxicity and skin lesions. SM exposed through percutaneous route was used to evaluate the prophylactic efficacy of various combinations. Low dose of DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide] with amifostine combinations, were given orally 30 min prior to SM exposure. Significant depletion was observed in body weight, organ body weight index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures.

• Authors: Anshoo Gautam, Alka Gupta, Vinay Lomash, S C Pant, R Vijayaraghavan
• Journal: Indian journal of experimental biology (Indian J Exp Biol) Vol. 48 Issue 7 Pg. 752-61 (Jul 2010) ISSN: 0019-5189 [Print] India
• PMID: 20929059 (Publication Type: Journal Article)

Chemical References

• Chemical Warfare Agents
• Radiation-Protective Agents
• S-2 (2-aminoethylamino)ethylphenylsulfide
• Glutathione
• Amifostine
• Mustard Gas

Topics

• Administration, Cutaneous
• Administration, Oral
• Amifostine (analogs & derivatives, chemistry, therapeutic use)
• Animals
• Body Weight (drug effects)
• Chemical Warfare Agents (toxicity)
• Drug Therapy, Combination
• Female
• Glutathione (metabolism)
• Mice
• Mustard Gas (toxicity)
• Organ Size (drug effects)
• Oxidative Stress (drug effects)
• Radiation-Protective Agents (therapeutic use)
• Skin Diseases (chemically induced, drug therapy, pathology)