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Comparative effects of aminotriazole on normal and acatalasemic mice
Abstract:
Some pharmacological and toxicological effects of dietary 3-amino-1,2,4-triazole (AT), a known catalase inhibitor, antithyroid agent, and carcinogen, have been examined, using acatalasemic (Csb) and normal catalase, "wild-type" (Csa) substrains of highly inbred C3H and C57BL mice. It was found that (a) the acatalasemic substrains are more resistant to weight loss and death on the AT diet than are their normal catalase counterparts; (b) Csb and Csa substrains of C57BL mice are more resistant to weight loss and death on the AT diet than are the Csb and Csa substrains of the C3H mouse; (c) the liver catalase, as well as the whole body catalase, of the two C57BL substrains is less inhibited by the AT diet than is that of the C3H substrains; (d) mice consuming the same quantity of either normal or AT-containing diet gain much more weight on the normal diet; (e) temporary consumption of the AT diet causes a considerable increase in thyroid weight, with an extremely slow, and only partial, return toward normal weight; and (f) the C3H/Csa mouse on an AT diet develops a scaly, necrotic tail very similar in appearance to the so-called rodent ringtail; this lesion is never observed in the acatalasemic mouse on the same diet.
Insights
Mice lacking catalase enzymes (acatalasemic) showed greater resistance to the toxic effects of 3-amino-1,2,4-triazole (AT) diet compared to normal mice. Strain differences also influenced resistance to AT toxicity.
Area of Science:
- Pharmacology
- Toxicology
- Biochemistry
Background:
- Dietary 3-amino-1,2,4-triazole (AT) is a known catalase inhibitor, antithyroid agent, and carcinogen.
- Catalase enzyme activity varies between mouse strains and substrains, impacting metabolic responses.
Purpose of the Study:
- To investigate the pharmacological and toxicological effects of AT in acatalasemic and normal catalase mice.
- To compare the susceptibility of different mouse strains (C3H and C57BL) to AT toxicity.
Main Methods:
- Administration of AT-containing diet to acatalasemic (Csb) and normal catalase (Csa) substrains of C3H and C57BL mice.
- Monitoring weight changes, mortality, liver and whole-body catalase inhibition, thyroid weight, and specific lesions (e.g., tail necrosis).
Main Results:
- Acatalasemic mice exhibited increased resistance to weight loss and death from AT compared to normal mice.
- C57BL substrains (both acatalasemic and normal) were more resistant to AT toxicity than C3H substrains.
- AT significantly inhibited catalase activity, increased thyroid weight, and induced tail necrosis in susceptible mice, with acatalasemic mice showing reduced severity.
Conclusions:
- Catalase activity plays a crucial role in mitigating the toxic effects of 3-amino-1,2,4-triazole.
- Genetic background (mouse strain) significantly influences the response to AT-induced toxicity.
- AT poses risks including antithyroid effects and carcinogenicity, with varying susceptibility based on catalase status and genetic factors.
