Excretion of porphyrins and porphyrin precursors during neuromuscular paralysis produced by dithiobiuret.
Urinary excretion of porphyrin precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) and total porphyrins was measured during intoxication of rats with 2,4-dithiobiuret (DTB), a chemical which produces delayed-onset neuromuscular weakness, in an attempt to ascertain whether or not DTB poisoning in the rat would serve as an animal model of the neurologic symptoms of acute intermittent porphyria. Daily administration of DTB (1 mg/kg/day, i.p.) produced flaccid skeletal muscle weakness first detected after 4 to 5 days of treatment. Onset of skeletal muscle weakness was associated with a significant increase in urinary excretion of ALA. The excretion of PBG and total porphyrin was also increased; however, the increase was not significant. The increase in porphyrins and porphyrin precursors was due to increased urine output which coincided with the onset of neuromuscular weakness; urinary concentrations of ALA, PBG, and porphyrins were not increased by DTB. Measurements of free-erythrocyte protoporphyrin, taken after 7 days of DTB treatment, indicated a significant elevation of free erythrocyte protoporphyrin concentration. The pattern of alterations in the heme precursors associated with DTB-induced paralysis in rats is quite different from that observed in humans afflicted with acute intermittent porphyria. Therefore, we conclude that DTB-induced paralysis in the rat does not represent an accurate animal model of acute intermittent porphyria.
D000622:Aminolevulinic Acid / Q000652:urine*; D000818:Animals; D004195:Disease Models, Animal; D007982:Levulinic Acids / Q000652:urine*; D008297:Male; D009123:Muscle Hypotonia / Q000652:urine; D009468:Neuromuscular Diseases / Q000139:chemically induced / Q000652:urine*; D010243:Paralysis / Q000139:chemically induced / Q000652:urine*; D011162:Porphobilinogen / Q000652:urine*; D011164:Porphyrias / Q000652:urine; D011166:Porphyrins / Q000652:urine*; D051381:Rats; D013890:Thiourea / Q000031:analogs & derivatives* / Q000633:toxicity; D013997:Time Factors
D007982:Levulinic Acids; D011166:Porphyrins; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D013890:Thiourea; C007540:2,4-dithiobiuret