Radioprotectors as late preventive agents against carbon tetrachloride induced liver necrosis: protection by 2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721).
Administration of the radioprotective agent 2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721) at 3 or 6 hr after carbon tetrachloride (CCl4) administration significantly prevented the liver necrosis produced by the hepatotoxin at 24 hr. It is well known that WR2721 does not exert or minimally exerts a protective activity by itself. The compound is activated through dephosphorylation to the free thiol WR1065, a process which is catalyzed by an alkaline phosphatase. We observed that this enzyme was widely distributed in the rat body. The WR2721 pretreatment 30 min before CCl4 administration modified the CCl4 levels reaching the liver at 1 hr of poisoning and exerted a significant increase in the covalent binding (CB) of 14CCl4-reactive metabolites to microsomal lipids at 3 hr. WR2721 did not modify the intensity of the CCl4-induced lipid peroxidation (LP) process at 1 or 3 hr of poisoning. CCl4-induced fat accumulation was not prevented when WR2721 was given 6 hr after CCl4. In fact, protection might be due to a favorable modulation of late events occurring after CB or LP, events that remain to be elucidated.
Valles
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EG
Centro de Investigaciones Toxicológicas (CEITOX), CITEFA/CONICET, Pcia. de Buenos Aires, Argentina.
de Castro
C R
CR
Castro
J A
JA
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D004999:Amifostine / Q000008:administration & dosage*; D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011837:Radiation-Protective Agents; D002251:Carbon Tetrachloride; D000469:Alkaline Phosphatase; D004999:Amifostine