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Anticonvulsant-induced changes in tissue manganese, zinc, copper, and iron concentrations in Wistar rats
J W Critchfield1, F G Carl, C L Keen
1Department of Nutrition, University of California, Davis 95616.
Abstract:
Human epileptics have been reported to have low blood manganese (Mn) concentrations in comparison to nonepileptics, an observation that is important because Mn deficiency can increase seizure susceptibility in experimental animals. Factors that have been suggested to contribute to the low blood Mn levels in epileptics include anticonvulsant use, seizure-induced tissue redistribution of Mn, and genetics; in the present study, the first of these possibilities was tested. Wistar rats were fed semipurified diets containing diphenylhydantoin ([DPH] 3 g/kg diet), phenobarbital ([PB] 2 g/kg diet), or primidone ([PRIM] 3 g/kg diet) for 7 weeks, at which time they were killed and tissues collected and analyzed for Mn, zinc (Zn), copper (Cu), and iron (Fe) concentrations. In comparison to pair-fed rats, DPH- and PRIM-fed rats had significantly elevated liver Mn concentrations, while Mn concentrations in blood, brain, heart, and kidney were unaffected by anticonvulsant exposure. Changes in the concentrations of Zn, Cu, and Fe in specific tissues were also found. Overall, these findings suggest that the anticonvulsants tested do not lead to significant derangements in the metabolism of Mn.
Insights
Anticonvulsant medications did not significantly alter manganese (Mn) levels in the blood or brain of rats. While some liver Mn increases were observed, overall Mn metabolism remained largely unaffected by diphenylhydantoin, phenobarbital, and primidone.
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- Human epileptics exhibit lower blood manganese (Mn) levels than nonepileptics.
- Mn deficiency in animals is linked to increased seizure susceptibility.
- Potential causes for low Mn in epileptics include anticonvulsant drugs, seizure activity, and genetics.
Purpose of the Study:
- To investigate whether common anticonvulsant medications affect manganese (Mn) levels in Wistar rats.
- To determine if diphenylhydantoin (DPH), phenobarbital (PB), or primidone (PRIM) alter Mn distribution in various tissues.
Main Methods:
- Wistar rats were administered semipurified diets containing DPH, PB, or PRIM for 7 weeks.
- Tissue samples (blood, brain, liver, heart, kidney) were collected and analyzed for Mn, zinc (Zn), copper (Cu), and iron (Fe) concentrations.
- Results were compared to pair-fed control rats.
Main Results:
- Diphenylhydantoin (DPH) and primidone (PRIM) significantly increased liver Mn concentrations compared to pair-fed controls.
- Mn concentrations in blood, brain, heart, and kidney were not significantly affected by DPH, PB, or PRIM exposure.
- Alterations in Zn, Cu, and Fe concentrations were observed in specific tissues.
Conclusions:
- The tested anticonvulsants (DPH, PB, PRIM) do not appear to cause significant disruptions in manganese (Mn) metabolism.
- Further research is needed to fully understand the relationship between anticonvulsant use and Mn levels in epilepsy.
