TITLE

In vivo protection by amifostine and DRDE-07 against sulphur mustard toxicity

AUTHOR(S)
Kumar, P; Vijayaraghavan, R; Kulkarni, A S; Pathak, U; Raza, S K; Jaiswal, D K
PUB. DATE
July 2002
SOURCE
Human & Experimental Toxicology;Jul2002, Vol. 21 Issue 7, p371
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The study was aimed at investigating the prophylactic efficacy of orally administered amifostine and a newly synthesized compound, S-2(2-amino-ethylamino)ethyl phenyl sulphide (DRDE-07), against dermally applied sulphur mustard (SM) in mice and rats. The LD[sub 50] values of amifostine and DRDE-07 were determined following oral and intraperitoneal routes and the LD[sub 50] of SM diluted in PEG-300 was determined following dermal route. Amifostine or DRDE-07 (equivalent to their 0.05 LD[sub 50], 0.10 LD[sub 50] and 0.20 LD[sub 50]) dissolved in water was fed to mice and rats and, after 30 min, various doses of SM were applied to the hair-clipped area of the skin and were observed for 14 days for mortality. The protection index (PI) was calculated as a ratio of LD[sub 50] with treatment to LD[sub 50] without treatment. The estimated percutaneous LD[sub 50] of SM was found to be 8.1 and 2.4 mg/kg for female mice and male rats, respectively. A dose-related protection was observed with all the three doses of both compounds. Thirty minutes prior, the administration of amifostine in female mice offered a PI of 3.0 at the lowest pretreatment dose (52.5 mg/kg) followed by PI of 6.7 and 9.5 at 105 and 210 mg/kg pretreatment doses, respectively. DRDE-07 offered better protection against SM in female mice, i.e., a PI of 4.8 at pretreatment dose of 62.5 mg/kg, a PI of 12.0 at the dose of 124.7 mg/kg and a PI of 27.0 at the dose of 249.4 mg/kg. In male rats, DRDE-07 gave a PI of about 3.0 at all the three pretreatment doses (80, 160 and 320 mg/kg), whilst amifostine offered a PI of 3.1 at the highest pretreatment dose (452 mg/kg). The present study showed that oral administration of both amifostine and DRDE-07 was effective as a prophylactic agent for protecting against SM toxicity, and that DRDE-07 offered better protection.
ACCESSION #
7216368

 

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