Late protective effects against CCl4-induced liver necrosis by the radioprotective agent 2-aminoethyl-isothiouronium...

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 CCl4 (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 CCl4 than when administered 30 min before. CCl4-induced fat accumulation was prevented only when AET was given 30 min before. AET did not prevent the CCl4-induced initiation of a lipid peroxidation (LP) process as evidenced by diene hyperconjugation of microsomal lipids. AET pretreatment 30 min before CCl4 did not significantly modify the CCl4 levels reaching the liver and only exerted a transient significant effect on the covalent binding of [14C]Cl4 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 h after CCl4 can not be attributed to decreased amounts of CCl4 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.