Dithiobiuret toxicity in the rat
Raising the daily dose of dithiobiuret (DTB) in male rats from 0.5 to 1 to 5 mg/kg shortened the latency to the onset of flaccid muscle tone and associated diminished performance in a treadmill test from 7 to 5 to 3 days, respectively. Concomitant with the development of flaccid muscle tone gastrocnemius muscle contractions elicited by high frequency motor nerve stimulation were lower in peak tension and tended to fade more rapidly in DTB-treated rats than in control rats. Remarkably, rats treated with highly daily doses (10-16 mg/kg) of DTB were resistant to the expected development of DTB-induced flaccid muscle tone, and tetanic contractile abnormalities but a corresponding refractoriness to body weight loss, decreased fed and water intake, diuresis, and depression in water balance was not present. This nonselectivity of the refractory responses supported the results of a histopathological study indicating that DTB-induced neuromuscular toxicity was unlikely to be secondary to effect on other organ systems. It is not known whether the ultimate neurotoxin is DTB or a metabolite. In this regard, two pathways for the metabolism of DTB were proposed based on the results of thin-layer chromatography of urine samples from rats treated with either /sup 14/C- or /sup 35/S-DTB. One pathway involved the reversible oxidation of DTB to the disulfide-containing compound thiuret, and the other involved the replacement of a sulfur atom with oxygen to form monothiobiuret. Thiuret, but not monothiobiuret, possessed comparable toxicity to STB. This further suggested that redox cycling between DTB and thiuret could be an important contributing factor to the toxicity of DTB.
- Research Organization:
- Wisconsin Univ., Madison (USA)
- OSTI ID:
- 6695789
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DITHIOLS
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MATERIALS
NERVOUS SYSTEM
NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIOISOTOPES
RATS
REAGENTS
RODENTS
SEPARATION PROCESSES
SULFUR 35
SULFUR ISOTOPES
THIN-LAYER CHROMATOGRAPHY
THIOLS
TOXIC MATERIALS
TOXICITY
TOXINS
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES