Phenytoin increases specific triacylglycerol fatty esters in skeletal muscle from horses with hyperkalemic periodic paralysis.
Previous studies have demonstrated that phenytoin decreases the levels of triacylglycerols in several tissues other than skeletal muscle. Since phenytoin is clinically effective in several skeletal muscle disorders, triacylglycerol metabolism in skeletal muscle from four normal Quarter horses and four Quarter horses with hyperkalemic periodic paralysis was examined. The horses with hyperkalemic periodic paralysis had low levels of 18:3 in the phospholipids, low levels of 16:0, 16:1 and 18:3 in the free fatty acids and low levels of 20:4 in triacylglycerols. Triacylglycerol levels were increased in skeletal muscle from seven (three controls, four hyperkalemic periodic paralysis) of the eight horses on treatment with oral phenytoin for one week. Instead of an increase in all fatty ester types only 16:0, 16:1, 18:1 and 18:2 were significantly increased. Total lipid phosphorus and the distribution of phospholipid fatty esters and free fatty acids were not significantly altered by phenytoin treatment in most cases. An alteration in triacylglycerol metabolism by phenytoin was also observed in primary cultures of normal equine skeletal muscle radiolabeled with 18:1, but not in those radiolabeled with 18:2. These findings suggest that phenytoin does not just increase the levels of triacylglycerol in skeletal muscle, but alters the utilization and incorporation of fatty esters. These findings suggest a potential involvement of triacylglycerol metabolism in the clinical efficacy of phenytoin in hyperkalemic periodic paralysis.
Fletcher
J E
JE
Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102-1192.
Erwin
K
K
Beech
J
J
D000818:Animals; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004952:Esters / Q000032:analysis*; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006734:Horse Diseases / Q000188:drug therapy / Q000378:metabolism*; D006736:Horses; D006947:Hyperkalemia / Q000150:complications / Q000662:veterinary*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D010243:Paralysis / Q000209:etiology / Q000662:veterinary*; D010672:Phenytoin / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
D002250:Carbon Radioisotopes; D004952:Esters; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D014280:Triglycerides; D010672:Phenytoin