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We have previously reported that a single meal of an arginine-free diet rapidly induces hyperammonemia in young ferrets and that aspirin administration in conjunction with influenza B infection and arginine-free diet results in clinical and biochemical alterations consistent with Reye's syndrome. The objective of the present study was to test whether ibuprofen administration, either alone or in combination with influenza infection and arginine-free diet, produces a similar effect. Two-mo-old ferrets were inoculated intranasally with influenza B virus, treated with therapeutic doses of ibuprofen, and fed a single meal of an arginine-free diet. Arginine-free diet caused a significant increase in plasma ammonia and a small increase in plasma aspartate aminotransferase activity. All ferrets fed an arginine-free diet recovered within 6 to 7 h after ingesting the diet. Ibuprofen treatment, either solely or in combination with influenza infection, did not produce significant change in the plasma levels of aspartate or ornithine aminotransferase activities. A combination of ibuprofen treatment, influenza infection, and arginine-free diet caused a significant increase in the mortality and plasma ammonia levels. Plasma aspartate aminotransferase and ornithine carbamyl transferase activities were elevated, and liver ornithine carbamyl transferase activity was decreased. However, other mitochondrial enzymes such as ornithine aminotransferase were not altered, whereas the activity of cytoplasmic enzymes such as arginase were decreased. These results suggest that ibuprofen administration resulted in generalized hepatopathy rather than specific mitochondrial injury and Reye's syndrome-like changes associated with aspirin in our previous model.

Interactions of Ibuprofen with Influenza Infection and Hyperammonemia in an Animal Model of Reye's Syndrome