Protection by 3-Amino-1, 2, 4-Triazole against the Lowered Uptake of p-Biphenylmethyl-(dl-Tropyl-α-Tropinium) Bromide into the Hepatic Lysosomes of Carbon Tetrachloride-treated Mice

Abstract

The effects of 3-amino-1, 2, 4-triazole (AT) on the uptake of tritiated p-biphenylmethyl-(dl-tropyl-α-tropinium) bromide (³H-BTTB) into the subcellular fractions of livers of carbon tetrachloride (CCl₄)-treated mice were studied. The uptake of ³H-BTTB into the liver of CCl₄-treated mice was decreased to 50% of that in the control group. Pretreatment with AT resulted in an effective restoration of the decrease caused by CCl₄ treatment up to the AT group's level, though AT itself lowered the uptake of ³H-BTTB to 61% of that of the control group. The subcellular distribution of ³H-BTTB in the liver of CCl₄-treated mice was different from that of the control : the ratio of the radioactivity in the lysosomal fraction to that of the supernatant fraction (the L/S ratio) was decreased by CCl₄ treatment from 1.85 to 1.66. This decrease was almost completely reversed to the control value by the pretreatment with AT and there was a similar change in the distribution of acid phosphatase. Furthermore, the cross-points of the lysosomes of the liver in mice which had been treated with CCl₄, AT and AT-CCl₄ were determined by means of cross-partition in aqueous polymer two-phase systems. CCl₄ made the surface charge of the lysosomal membrane more acidic, though AT reversed this change. There may be an important relationship between the uptake of BTTB into lysosomes and the characteristics of the lysosomal membranes.