Reduction of the toxicity of ‘radiomimetic’ alkylating agents in rats by thiol pretreatment—III

Connors, T. A.; Jeney, A. v.; Jones, Mark

doi:10.1016/0006-2952(64)90209-6

Cited by 28 publications

(5 citation statements)

References 6 publications

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“…Sodium thiosulphate and N -acetylcysteine have been considered, although the acute clinical efficacy of these agents has yet to be established. Sodium thiosulphate infusion (10%) may prevent the toxic manifestations of SM, providing it is administered immediately after an exposure and no later than 30 min after exposure 103, 104. There is no specific treatment for the delayed toxic effects and complications of SM in different target organs.…”

Section: Managementmentioning

confidence: 99%

Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

Balali‐Mood¹,

Mousavi²,

Balali-Mood³

2008

EHTJ

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The widespread use of sulphur mustard (SM) as an incapacitating chemical warfare agent in the past century has proved its long-lasting toxic effects. It may also be used as a chemical terrorist agent. Therefore, all health professionals should have sufficient knowledge and be prepared for any such chemical attack. SM exerts direct toxic effects on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, immunological, haematological, digestive, and reproductive systems. SM is an alkylating agent that affects DNA synthesis, and, thus, delayed complications have been seen since the First World War. Cases of malignancies in the target organs, particularly in haematopoietic, respiratory, and digestive systems, have been reported. Important delayed respiratory complications include chronic bronchitis, bronchiectasis, frequent bronchopneumonia, and pulmonary fibrosis, all of which tend to deteriorate with time. Severe dry skin, delayed keratitis, and reduction of natural killer cells with subsequent increased risk of infections and malignancies are also among the most distressing long-term consequences of SM intoxication. However, despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Immunological and neurological dysfunction, as well as the relationship between SM exposure and mutagenicity, carcinogenicity, and teratogenicity are important fields that require further studies, particularly on Iranian veterans with chronic health effects of SM poisoning. There is also a paucity of information on the medical management of acute and delayed toxic effects of SM poisoning—a subject that greatly challenges health care specialists.

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Section: Managementmentioning

confidence: 99%

Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

Balali‐Mood¹,

Mousavi²,

Balali-Mood³

2008

EHTJ

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“…SM is a frequently used chemical warfare agent, and several reports are available of its recent use. − SM forms the sulfonium ion in the body and alkylates DNA, leading to DNA strand breaks and cell death − Several compounds have been evaluated for reducing the systemic toxicity of SM but with limited protection. − So far, no accepted antidote is available for SM and the treatment is symptomatic.…”

Section: Introductionmentioning

confidence: 99%

Novel S-Substituted Aminoalkylamino Ethanethiols as Potential Antidotes against Sulfur Mustard Toxicity

et al. 2004

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Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory treatment regimen is not yet available for this toxicant. In a search for an effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky, alicyclic, aryl, and heterocyclic substituents, have been designed and synthesized as candidate antidotes against SM toxicity. These compounds were screened for their protective efficacy through the oral route against dermally applied sulfur mustard in female mice measured on the basis of percent survival following percutaneous administration of SM. A number of compounds demonstrated significant protection.

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“…At pH 6.3 none of the compounds tested appeared to be toxic in concentrations up to 100mM as is demonstrated for cysteamine and thioglycol by curves (a) of respectively figures 2 and 4. Since Na 2 S 2 0 3 cannot penetrate into the cell (Connors, Jeney and Jones 1964) as is the case with CN-, this might indicate that the toxicity of cysteamine develops, at least partly, intracellularly. Especially thioglycol, which demonstrated hardly any toxicity at pH 73, appeared to be much more toxic at pH 8-3 (figure 4).…”

Section: Protection By Sulphydryl Compoundsmentioning

confidence: 99%

Protection against X-irradiation by Sulphydryl Compounds

Vergroesen

Budke

Vos

1967

International Journal of Radiation Biology and Related Studies

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The radioprotective effect of eight thiol compounds with pK-values of their thiol groups varying from 8'5-10'8 was tested on isolated cells in vitro. The influence of variations in pH of the incubation medium between 6-3 and 83 was investigated. The ability of the cells to form colonies was used as the criterion for survival.By comparing the protection affected by different concentrations of the various compounds it was found that a good correlation existed between the degree of radio-protection and the thiolate concentration in the medium. This correlation was also found to be present under anoxic conditions. It was concluded that the increase of the radio-protective activity of the thiol compounds, caused by an increase of either concentration, pH or temperature, can be explained by an increase of the amount of thiol compound present inside the cell. The differences in radio-protective activity of the various compounds cannot be explained by differences in cellular uptake.The thiol compounds with a pK-value lower than 10 appeared to be very toxic at concentrations between 01 and 2-0 mM, but not at concentrations lower than 0-1 mM and between 2 to c. 100 mM. This striking toxicity could be prevented by incubation under anoxic conditions, by a decrease of the pH to 63, by addition of an excess of another thiol compound or of KCN, but not by addition of NaS,0 3 . The toxic action of the thiol compounds at these concentrations seems to be caused by an irreversible intracellular reaction of a specific oxidation product of these compounds with some cellular constituant.

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Reduction of the toxicity of ‘radiomimetic’ alkylating agents in rats by thiol pretreatment—III

Cited by 28 publications

References 6 publications

Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

Novel S-Substituted Aminoalkylamino Ethanethiols as Potential Antidotes against Sulfur Mustard Toxicity

Protection against X-irradiation by Sulphydryl Compounds

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