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

Kumar, P; Vijayaraghavan, R; Kulkarni, A S; Pathak, U; Raza, S K; Jaiswal, D K
July 2002
Human & Experimental Toxicology;Jul2002, Vol. 21 Issue 7, p371
Academic Journal
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.


Related Articles

  • Toxicology of nanoparticles. A. Durnev // Bulletin of Experimental Biology & Medicine;Jan2008, Vol. 145 Issue 1, p72 

    Abstract  The paper considers the basic directions in fundamental and applied studies of the toxic effects of nanoparticles. Of particular importance is the study aimed at evaluation of the dependence of these effects on the shape, size, initial material, surface area, electric charge, and...


    Chemical warfare agents (CWA's) induce complex toxicological effects with major adverse consequences for those exposed. For many chemical agents there is a need for research and development of analytical toxicological methods for a rapid and certain confirmation of those exposures. The certain...

  • Inhibition of blood and tissue cholinesterases by soman in guinea pigs in vivo.  // Journal of Applied Biomedicine (De Gruyter Open);Mar2011, Vol. 9 Issue 1, p35 

    No abstract available.

  • Inhibition of blood and tissue cholinesterases by soman in guinea pigs in vivo.  // Journal of Applied Biomedicine (De Gruyter Open);Mar2011, Vol. 9 Issue 1, p35 

    No abstract available.

  • The Fanconi anemia pathway in replication stress and DNA crosslink repair. Jones, Mathew; Huang, Tony // Cellular & Molecular Life Sciences;Dec2012, Vol. 69 Issue 23, p3963 

    Interstand crosslinks (ICLs) are DNA lesions where the bases of opposing DNA strands are covalently linked, inhibiting critical cellular processes such as transcription and replication. Chemical agents that generate ICLs cause chromosomal abnormalities including breaks, deletions and...

  • A review on organophosphorus toxicity in the farmers of solapur district from India. Bhagwat, Kale // International Journal of Biological Research;2014, Vol. 2 Issue 2, p69 

    Organophosphorus compounds were first developed by scientist Schrader shortly before and during Second World War. They were first used as agricultural insecticides and later as potential chemical warfare agent. A great proportion of acute poisoning cases are caused by exposure to these...

  • Chapter 19: A Test Battery of Combined Methods to Determine Cytotoxic Effects of Sulfur Mustard and to Investigate Cytoprotective Effects of PARP Inhibitors. BALSZUWEIT, F.; HEINRICH, A.; KEHE, K.; THIERMANN, H. // Journal of Medical Chemical, Biological & Radiological Defense;2010, Vol. 8, p136 

    Sulfur mustard (SM) is a strong alkylating agent, interacting both with DNA/RNA as well as proteins. As a consequence, apoptotic and/or necrotic cell death is induced. PARP over-activation has been shown as a result of SM-induced DNA damage and may modify the mode of cell death and subsequent...

  • Long-term Psychological Consequences among Chemical Warfare Survivors of World War I and their Current Relevance. Jones, Edgar; Greenberg, Neil // Psychiatric Annals;Nov2007, Vol. 37 Issue 11, p724 

    The article discusses battlefield, post-war, long term and current exposure responses to chemical warfare among U.S. and British survivors of World War I, World War II and the Gulf War. Studies show that although death was rapid to directly exposed service men, mild exposure cases have long term...

  • The skin notation in the MAC list and classification of dangerous chemicals. Kupczewska-Dobecka, Małgorzata; Czerczak, Sławomir; Kupczewska-Dobecka, Małgorzata; Czerczak, Sławomir // International Journal of Occupational Medicine & Environmental H;Apr2006, Vol. 19 Issue 2, p84 

    The European Union has published a list of dangerous chemicals, along with classification and labeling; in 1997 the list was adapted to the requirements of Polish regulations and has been continuously updated since then. We have decided to adopt data on dangerous chemicals classification in the...

  • A simple and effective method for detecting toxicity of chromium trioxide on Vicia faba. Duan, Peilu; Zhai, Tianlong; Xu, Cunji; Ding, Jingna; Chen, Yan // European Food Research & Technology;Mar2013, Vol. 236 Issue 3, p517 

    In modern biological research, there are many analytical methods to evaluate the toxicity caused by chemical agents, such as higher plant bioassay, flow cytometry, single-cell gel electrophoresis or the comet assay. However, these methods are either tediously experimental procedures or require a...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics