Phenytoin increases specific triacylglycerol fatty esters in skeletal muscle from horses with hyperkalemic periodic paralysis.
Abstract: 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.
Publication Date: 1993-07-01 PubMed ID: 8323969DOI: 10.1016/0005-2760(93)90185-cGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research studied the effects of phenytoin, a type of medication, on the fat chemistry in horse muscles, specifically in relation to a condition known as hyperkalemic periodic paralysis. It found that phenytoin did not simply increase the levels of one type of fat, triacylglycerol, but altered how different types of fats, or fatty esters, are utilized and incorporated.
Objective and Study Participants
- The objective was to examine the metabolism of a particular type of fat, or lipid, known as triacylglycerol (TAG), in skeletal muscle, specifically in the context of a horse muscular disorder called hyperkalemic periodic paralysis (HYPP).
- For this study, muscle tissues from four normal horses and four horses suffering from HYPP were analyzed.
Method and Observations
- All horses were treated with phenytoin orally for one week. Phenytoin is a commonly used medication in several muscular disorders.
- Differences in the levels of particular fatty esters – 16:0, 16:1, 18:1, 18:2, 18:3, and 20:4 (these denote types of fats) – in the phospholipids, free fatty acids, and TAGs between normal horses and those affected by HYPP were measured before and after treatment.
- The researchers observed that horses suffering from HYPP had decreased levels of 18:3 in phospholipids, low levels of 16:0, 16:1, 18:3 in free fatty acids, and 20:4 in TAGs.
- On administration of phenytoin, the levels of TAG were seen to increase in seven out of the eight horses. However, they noticed that not all types of fatty esters increased – just the fatty esters 16:0, 16:1, 18:1, and 18:2 increased significantly.
Phenytoin’s Impact and Conclusions
- On most occasions, elements like lipid (fat) phosphorus and the distribution of phospholipid fatty esters and free fatty acids did not significantly change due to phenytoin treatment.
- Experiments with primary cultures of normal equine skeletal muscle demonstrated similar alterations in TAG metabolism when treated with phenytoin.
- The study concludes that phenytoin doesn’t just increase the levels of TAG in skeletal muscle tissue, but impacts how different types of fatty esters are used and incorporated in the body.
- The researchers suggest that this ability of phenytoin to alter TAG metabolism could play a key role in its clinical effectiveness in treating HYPP.
Cite This Article
APA
Fletcher JE, Erwin K, Beech J.
(1993).
Phenytoin increases specific triacylglycerol fatty esters in skeletal muscle from horses with hyperkalemic periodic paralysis.
Biochim Biophys Acta, 1168(3), 292-298.
https://doi.org/10.1016/0005-2760(93)90185-c Publication
Researcher Affiliations
- Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102-1192.
MeSH Terms
- Animals
- Carbon Radioisotopes
- Cells, Cultured
- Esters / analysis
- Fatty Acids / metabolism
- Fatty Acids, Unsaturated / metabolism
- Horse Diseases / drug therapy
- Horse Diseases / metabolism
- Horses
- Hyperkalemia / complications
- Hyperkalemia / veterinary
- Muscles / drug effects
- Muscles / metabolism
- Paralysis / etiology
- Paralysis / veterinary
- Phenytoin / pharmacology
- Phospholipids / metabolism
- Triglycerides / metabolism
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