Different acute effects of oral and intratracheal administration of disodium arsenate and gallium arsenide on heme synthesis in rats

Abstract

The acute influences of arsenic compounds on the metabolism of porphyrins and heme in various organs of rats after oral or intratracheal administration of disodium arsenate (Na,HAsO,) and gallium arsenide (GaAs) were examined and compared.For the oral administration experiments, 21 or 84 mg of Na,HAsO,, or 2 or 4 g of GaAs, per cm3 saline per kg body weight of each animal was administered to Jcl: Wistar male rats and the organs were removed after exsanguination from the vein of the right axilla under anesthesia with ether, 16h after administration. In the case of intratracheal administration, rats given 8.2 or 16.4mg of Na,HAsO,, or 0.2 or 0.4g GaAs per cm3 saline per kg body weight were examined under the same experimental conditions as for the administration route.Increase in the body weight of rats was suppressed after intratracheal administration of the two arsenic compounds. In these rats the hematocrit value increased significantly. These changes were not shown by the orally administered rats. Elevation in 6-aminolevulinate synthase (ALA-S, EC 2.3.1.37) activity in erythroblasts by Na,HAs04 was much higher after intratracheal administration than after oral administration. Suppression in the activities of 6-aminolevulinate dehydratase (ALA-D, EC 4.2.1.24) and porphobilinogen deaminase (PBG-D, EC 4.3.1.8) in peripheral erythrocytes by NazHAsO, and GaAs were stronger by intratracheal administration than by the oral route. Influences of GaAs on the activity of PBG-D in rat liver were shown to be more effective by oral administration than by the intratracheal route. Oral administration of Na,HAsO, $ Author to whom all correspondence should be sent, at The Institute of Public Health, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108 Japan. It seems from these results that the different extents of the influence of arsenic compounds might depend on the routes of intake.

Acute effects of orally administered sodium arsenate on heme biosynthetic enzymes in the tissues of three strains of mice

“…8 In our previous investigations on Wistar rats and ICR mice, we found that the effects of a single oral administration of As(V) on heme biosynthetic enzyme activities varied in magnitude from one animal species to another and between the sexes and organs or tissues within a given species. [9][10][11] In particular, we found that administration of As(V) markedly decreased the activities of the heme biosynthetic enzymes in the spleen of mice of the ICR strain, 9,11 although little effect on these activities was noted in rat bone marrow cells. …”

“…10,11 Heparinized blood was collected and the liver perfused through the portal vein with cold saline. Kidneys and spleens were carefully removed and weighed.…”

“…Supernatant and precipitation fractions were prepared from the homogenates by centrifugation at 48 800g for 30 min. 10,11 The precipitation fraction was further washed twice with 0.25 M sucrose solution, resuspended in the same solution and used for the ALAS assay. The supernatant fraction and whole-blood lysates were used for the assay of ALAD and PBGD.…”

“…[9][10][11] In particular, we found that administration of As(V) markedly decreased the activities of the heme biosynthetic enzymes in the spleen of mice of the ICR strain, 9,11 although little effect on these activities was noted in rat bone marrow cells. 10 It is well known that among several strains of mice, the selection of a suitable strain for use in a particular experiment depends upon the objective of the study. [12][13][14][15] Gross and Hulton 14 measured the activity of d-aminolevulinate synthase (ALAS) in 15 strains of inbred mice and reported finding little difference among them.…”

Acute Effect of Orally Administered Gallium Arsenide, Gallium Nitrate and Disodium Arsenate on Heme Synthesis in Male and Female Mice

“…Changes in PBGD activity were observed to occur in Ga(NO,),-treated females and in Na,HAsO,-treated males, but no distinct dose-response relationship was observed for the activity level of either of these enzymes (Tables 7,8).…”