Late protective effects against CCl 4-induced liver necrosis by the radioprotective agent 2-aminoethyl-isothiouronium bromide hydrobromide (AET)

Abstract

Administration of the radioprotective agent 2-aminoethyl-isothiouronium bromide hydrobromide (AET) (240 mg/kg, i.p. in saline 30 min before or 6 or 10 h after CCl 4 (1 ml/kg i.p. as a 20% v/v solution in olive oil) significantly prevented the necrogenic effect of the hepatotoxin at 24 h. Protection was more intense when the drug was given 6 h after CCl 4 than when administered 30 min before. CCl 4-induced fat accumulation was prevented only when AET was given 30 min before. AET did not prevent the CCl 4-induced initiation of a lipid peroxidation (LP) process as evidenced by diene hyperconjugation of microsomal lipids. AET pretreatment 30 min before CCl 4 did not significantly modify the CCl 4 levels reaching the liver and only exerted a transient significant effect on the covalent binding of [ 14C]Cl 4 reactive metabolites to microsomal lipids (CB) at 1 h but not at 3 h. The markedly intense protective effects of AET when given 6 or 10 after CCl 4 can not be attributed to decreased amounts of CCl 4 reaching the liver or to decreasing effects in CB or to chain breaking effects in LP. Really, protection might be due to a favorable modulation of late events occurring after CB or LP, events that remain to be elucidated.