The role of the methylation in the detoxication of arsenate in the rabbit.
The biotransformation, tissue retention, intracellular binding and biokinetics of arsenic were studied in rabbits exposed to [74As]arsenate (0.4 mg As/kg body wt., i.v.). Inhibition of the methyltransferase activity by injection of periodate-oxidized adenosine (PAD) caused a marked decrease of the formation of [74As]dimethylarsinic acid (DMA), which gave rise to 1.5-4 times increased tissue levels of 74As. This is almost the same as reported for rabbits given arsenite in combination with PAD and was due to a rapid reduction of the arsenate to arsenite which bound to the tissues. Only about 30% of the arsenate given was excreted unchanged in the urine, indicating that a large part was reduced to AsIII. Thus the methylation to DMA seems to be almost as important for the detoxication following exposure to arsenate as that following exposure to arsenite. In the rabbits with normal methylating capacity 50-70% of the produced AsIII was methylated to DMA. The liver was the only organ in which DMA was present 1 h after the administration, indicating that this is the main site of the methylation. The DMA was rapidly cleared from all tissues except the thyroid.
D000818:Animals; D001149:Arsenates / Q000378:metabolism* / Q000633:toxicity; D001151:Arsenic / Q000378:metabolism*; D001711:Biotransformation; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008745:Methylation; D011817:Rabbits; D011868:Radioisotopes; D014018:Tissue Distribution
D001149:Arsenates; D011868:Radioisotopes; D001151:Arsenic; C025657:arsenic acid