ABSTRACT
The lysosomotropic amines methylamine (40 mM) and chloroquine (125 mM) prevented the killing of cultured hepatocytes by hydrogen peroxide generated in the medium by glucose oxidase. Maximum protection required several hours preincubation with either amine. Sensitivity of the hepatocytes to H2O2 was restored either by the addition of ferrous or ferric iron to the culture medium, or by incubating the cells for 4 hours in the absence of either amine prior to treatment with H2O2. Neither methylamine nor chloroquine had any effect on the cell killing by t-butyl hydroperoxide, a hepatotoxin that does not require iron. The protective effect of the lysosomotropic amines was distinguished from that of the ferric iron chelator deferoxamine in two ways: 1) deferoxamine protected hepatocytes from H2O2 toxicity but did not require a pretreatment period; and 2) in contrast to methylamine or chloroquine, deferoxamine had no effect on lysosomal pH as assessed by the fluorescent probe acridine orange. The data suggest that a lysosomal pool is the source of the ferric iron necessary for the killing of hepatocytes by H2O2.
Subject(s)
Cell Survival/drug effects , Ferric Compounds/physiology , Hydrogen Peroxide/toxicity , Iron/physiology , Liver/metabolism , Lysosomes/metabolism , Animals , Chloroquine/pharmacology , Deferoxamine/pharmacology , Ferric Compounds/metabolism , Hydrogen Peroxide/metabolism , Hydrogen-Ion Concentration , In Vitro Techniques , Male , Methylamines/pharmacology , Oxidation-Reduction/drug effects , Rats , Rats, Inbred StrainsABSTRACT
The effect of primary aliphatic alcohols of varying chain length and degree of unsaturation on bacterial growth was assessed, using Strep. mutans BHT as the main test organism. Unsaturated alcohols, linoleyl and linolenyl, effectively inhibited bacterial growth. Of the saturated alcohols, only lauryl and myristyl alcohols inhibited the growth of Strep. mutans BHT, but at concentrations much higher than those required for the unsaturated alcohols. All Gram-positive organisms tested were sensitive to linolenyl alcohol. Gram-negative bacteria did not exhibit the sensitivity. Linoleic and linolenic acid were inactive as antibacterial agents at the same concentration as the related alcohol. Repeated exposure of Strep. mutans BHT to linolenyl alcohol produced no change in the sensitivity of the organism to the alcohol. Significant amounts of linolenyl alcohol were found in bacteria grown in the presence of this lipid for 24 h but linolenic acid was not detected. Thus the primary polyunsaturated aliphatic alcohols, particularly linolenyl alcohol, could be effective antibacterial agents for the prevention of dental caries and periodontal disease.
