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Phenytoin-induced serum copper and ceruloplasmin in C57BL/6J mice of different ages

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Phenytoin (diphenyihydantoln) given orally to male C57BL/6J mice increased the serum copper and ceruloplasmin concentrations. Young adult mice showed a maximum increase of 107% in ceruloplasmin accompanied by a 102% increase in copper. The ceruloplasmin of middle-aged mice increased 53% and the copper 64%. For old mice the corresponding increases were 20 and 21%. Phenytoin was toxic to old mice, and middle-aged mice experienced a higher rate of death when given phenytoin for 167 days.

After 14 days, phenytoin decreased liver copper by 18% without significantly changing copper levels in kidney, brain or heart. Feeding phenytoin for 167 days lowered liver copper by 14%, increased kidney by 9% and brain by 25%. Copper in the heart remained unchanged.

We proposed that the status of copper in the brain may be important in epilepsy.

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Massie, H.R., Colacicco, J.R. & Aiello, V.R. Phenytoin-induced serum copper and ceruloplasmin in C57BL/6J mice of different ages. AGE 3, 33–37 (1980). https://doi.org/10.1007/BF02432193

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