Age dependence of dithiobiuret neurotoxicity in male and female rats
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Abstract:
Weanling, juvenile and adult rats both sexes were treated with 1 mg/kg/day [14C] dithiobiuret (DTB) until they developed skeletal muscle weakness as detected by failure in a rotarod test. The latent period before the onset of weakness was longest in weanling animals of both sexes. The greater resistance of the weanlings, to DTB intoxication, could not be explained by differences in the cumulative body burden or tissue distribution of DTB and its metabolites. The sex of the animal was not a determinant of DTB toxicity. Urine and feces were the major and minor routes, respectively, for elimination of DTB and its metabolites in all animals. However, weanlings excreted relatively less 14C by the urinary route and more by the fecal route when compared to adults. These findings demonstrated the age dependence of DTB neurotoxicity in rats and show that it is not caused by differences in either the cumulative body burden or tissue distribution of DTB-derived [14C].
Insights
Younger rats show greater resistance to dithiobiuret (DTB) neurotoxicity. This age-dependent resistance in weanling rats is not due to DTB body burden or distribution differences.
Area of Science:
- Toxicology
- Neuroscience
- Pharmacokinetics
Background:
- Dithiobiuret (DTB) is a chemical agent known to cause neurotoxicity.
- The impact of age on DTB toxicity has not been fully elucidated.
Purpose of the Study:
- To investigate the age-dependent effects of DTB neurotoxicity in rats.
- To determine if age influences DTB accumulation, distribution, or excretion.
Main Methods:
- Rats of different ages (weanling, juvenile, adult) were administered [14C]DTB until skeletal muscle weakness occurred.
- Rotarod tests were used to assess neurobehavioral deficits.
- Radioactivity in urine and feces was measured to track DTB elimination.
Main Results:
- Weanling rats exhibited the longest latency period before developing muscle weakness, indicating greater resistance.
- DTB toxicity was not influenced by the animal's sex.
- While urine and feces were primary excretion routes for all ages, weanlings showed relatively less urinary and more fecal excretion of 14C.
Conclusions:
- DTB neurotoxicity is age-dependent in rats, with younger animals being more resistant.
- This resistance is not explained by differences in cumulative DTB body burden or tissue distribution.
- Age-related variations in excretion pathways may contribute to differential DTB toxicity.