Radioprotectors as Late Preventive Agents against Carbon Tetrachloride Induced Liver Necrosis: Protection by 2-(3-Aminopropylamino) Ethylphosphorothioic Acid (WR2721)

Vallés, Elena; Castro, Clementina; Castro, J.A.

doi:10.1006/exmp.1995.1034

Cited by 9 publications

(3 citation statements)

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“…A significant reduction in the relative weight of liver and spleen was observed in the present study and pretreatment with the effective analogues protected them. The liver is the main organ for detoxification and the beneficial effects of analogues may be related to their hepatoprotective potential, since all these analogues were developed from amifostine which has very good hepatoprotective activity (Valles et al, 1995).…”

Section: Effect Of Analogues On Histological Lesions Induced By Sm Inmentioning

confidence: 99%

Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous route

et al. 2006

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Sulfur mustard (SM), chemically bis (2-chloroethyl) sulfide is a bifunctional alkylating agent that causes serious blisters on contact with human skin. Although several antidotes have been reported for the systemic toxicity of SM in experimental animals none of them are approved so far and decontamination of SM immediately by physical or chemical means is recommended as the best protection. Two compounds amifostine [S-2(3-aminopropylamino) ethyl phosphorothioate] and DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulfide] gave very good protection as an oral prophylactic agent against SM the in mouse model, but in the rat model the protection was only moderate. In the search for more effective and less toxic compounds, a number of analogues of DRDE-07 were synthesised and their protective efficacy was evaluated in mouse and rat models. The LD50 of S-aryl substitution was between 1 and 2 g kg(-1) and S-alkyl substitution was more than 2 g kg(-1). In the mouse model, DRDE-07, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 gave about 20 fold protection, and DRDE-23 and DRDE-38 gave less protection of 4.8 and 9.0 fold respectively, against percutaneously administered SM. In the rat model, DRDE-07, DRDE-09, DRDE-10 and DRDE-21 gave about two fold protection. Percutaneously administered SM (19.33 mg kg(-1)) significantly depleted the hepatic GSH content in mice. Pretreatment with DRDE-21 significantly elevated the levels. A 4.4 fold increase in % DNA fragmentation was observed 7 days after SM administration (19.33 mg kg(-1)) in mice. Pretreatment with DRDE-07, DRDE-09, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 significantly protected the mice from SM induced DNA damage. The histopathological lesions in liver and spleen induced by percutaneously administered SM was reduced by pretreatment with DRDE-07, DRDE-09, DRDE-10 and DRDE-21. These analogues may prove as prototypes for the designing of more effective prophylactic drug for SM.

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Section: Effect Of Analogues On Histological Lesions Induced By Sm Inmentioning

confidence: 99%

Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous route

et al. 2006

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“…It protects against lipoperoxidation, increases intracellular glutathione, interferes with the cross-linking of DNA, assists in the repair of damaged DNA, and may have mechanisms yet to be identified (29 -31). Amifostine has been shown to prevent carbon tetrachloride-induced liver necrosis up to 6 h after poisoning which may be due to a mechanism other than interruption of redox cycling (32). These characteristics may potentially attenuate ongoing hepatic necrosis.…”

Section: Introductionmentioning

confidence: 99%

Use of Amifostine, a Novel Cytoprotective, in α-Amanitin Poisoning

Wills¹,

Haller²,

Polizzi³

et al. 2005

LCLT

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“…Amifostine, when given prophylactically for chemotherapeutic agents like cisplatin and cyclophosphamide, has been shown to protect selectively normal tissues without reducing the cytotoxic effects on the cancer cells [24][25][26][27] . Amifostine has also been shown to be effective against carbon tetrachlorideinduced liver necrosis, and to protect tissues from the toxicities of radiation and alkylating agents, probably by scavenging the generated free radicals 25,[28][29][30] . This triggered interest of the authors in amifostine and its analogues as a prophylactic agent against SM toxicity.…”

Section: Vt (Tidal Volume) T I (Time Of Inspiration) T E (Time Of Expmentioning

confidence: 99%

Respiratory Effects of Amifostine and DRDE-07: Probable Prophylactic Agents of Sulphur Mustard in Rats

Singh

Malviya²,

Gautam

et al. 2006

DSJ

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Amifostine (S-2[3-aminopropylamino]ethyl phosphorothioate) and one of its analogues, DRDE-07 (S-2[2-aminoethylamino]ethyl phenyl sulphide) are promising prophylactic agents for sulphur mustard (SM; a blistering agent) toxicity. When given orally, DRDE-07 was more effective than amifostine as a prophylactic agent against SM administered percutaneously. Various pharmacological and toxicological studies are required before the introduction of a chemical as a drug. The respiratory effects of amifostine and DRDE-07 were carried out in rats using a body plethysmograph fitted with a volumetric pressure transducer for sensing the respiratory flow signals. The signals were amplified, digitised, and stored on a personal computer for further analysis. After taking control recordings of respiratory signals, different doses (0.5 LD 50 , 1.0 LD 50 and 2.0 LD 50 ) of amifostine and DRDE-07 were administered orally (LD 50 amifostine = 2262 mg/ kg; DRDE-07 = 1599 mg/kg), and the respiratory changes were monitored for 4 h. Amifostine and DRDE-07 showed a uniform breathing pattern even in 2.0 LD 50 dose. However, a significant dosedependent decrease in respiratory frequency was observed following amifostine administration. DRDE-07 did not show any significant change. The tidal volume was not altered significantly both in amifostine and DRDE-07 administered animals. The study shows that DRDE-07, even in lethal doses, may not affect the respiration immediately, whereas, amifostine may decrease the respiratory frequency.

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Radioprotectors as Late Preventive Agents against Carbon Tetrachloride Induced Liver Necrosis: Protection by 2-(3-Aminopropylamino) Ethylphosphorothioic Acid (WR2721)

Cited by 9 publications

References 0 publications

Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous route

Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous route

Use of Amifostine, a Novel Cytoprotective, in α-Amanitin Poisoning

Respiratory Effects of Amifostine and DRDE-07: Probable Prophylactic Agents of Sulphur Mustard in Rats

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