Effects of Bal and Bal Glucoside in Acute Lead Acetate Poisoning

Abstract

2: 3-Dimercaptopropanol (BAL) was described by Peters, Stocken, and Thompson (1945) as an antidote to lewisite and other forms of arsenical poisoning. It has also been found to protect animals poisoned by several other heavy metals, but so far as is known the only data on its effect in lead poisoning are those of Braun, Lusky, and Calvery (1946), who found that after single or repeated intraperitoneal injections of lead nitrate into rabbits courses of BAL increased the mortality above that of control groups of animals. The experiments reported in the present paper are part of a study of the action of BAL and other dithiols in lead poisoning. MATERIALS AND METHODS MaterialsThe BAL used in this investigation was a waterpurified sample kindly presented by Prof. R. A. Peters. It was stored in a refrigerator and solutions were prepared freshly as required. Solutions of BAL glucoside (Danielli, Danielli, Mitchell, Owen, and Shaw, 1946) were prepared from its barium salt by liberating the free dithiol with sulphuric acid, precipitating any residual barium with sodium sulphate and removing the precipitate by centrifuging. The strength of the solutions was estimated by iodine titration before use; thjL gave somewhat variable results, but was more satisfactory than computing the strength from the amount of barium salt used, as the latter varied considerably in its thiol content. The doses quoted must be regarded as only approximate. Red cell fragility experimentsFreshly prepared, heparinized, and washed rabbit red blood cells were allowed to react with lead acetate or BAL or plasma or mixtures of these, usually for one hour at room temperature. Their fragility was then determined by adding aliquots to a series of sodium chloride solutions ranging from 0.28 to 0.64 per cent (w/v) at intervals of 0.04 per cent, centrifuging and estimating the haemoglobin concentration in the supernatant fluid by visual comparison with standards at 20 per cent intervals prepared from a water-laked suspension of the same red cells. The percentage lysis plotted against the salt concentration gave a sigmoid curve from which the 50 per cent lytic concentration (LyC50) was obtained graphically. The probit of the percentage lysis plotted against the logarithm of the salt concentration allowed a straight line to be fitted fairly closely; such lines did not give a substantially different estimate of the LyC50 and were used only when a quantitative estimate of the slope was required. For measurements in vivo the same procedure was followed, except that aliquots of the washed cell suspensions were added immediately and without other manipulation to the series of sodium chloride dilutions. Blood estimationsReticulocyte and red cell counts were performed by the usual techniques. Haematocrits were determined in capillary tubes of 0.1 ml. capacity. Haemoglobin was estimated in early experiments as carboxyhaemoglobin by means of a dilution comparator and later as cyanmethaemoglobin (King, Gilchrist, and Delory, 1944) by means of a Hilger Spekker absorptiom...