Hepatic lipid abnormalities in a chemical/viral mouse model for Reye's syndrome.
We have examined hepatic lipid profiles in a mouse model for Reye's Syndrome (RS) in which young animals are exposed to nontoxic doses of an industrial pesticide emulsifier and subsequently are infected with sublethal doses of mouse-adapted human Influenza B (Lee) virus (FluB). The purpose of this study was to determine whether liver lipid content was altered in the mice, the time course of any changes, and whether lipid changes were consistent with liver pathology. Neonatal mice exposed dermally to the emulsifier, Toximul MP8 (Tox), had significantly elevated levels of hepatic cholesterol, with otherwise normal lipid composition. Subsequent inoculation of the mice with FluB significantly increased mortality rate. The combined Tox + FluB treatment had several significant effects on liver lipids, including a transient increase in phospholipid (PL) content, a reduction in neutral glycerides and persistently high cholesterol levels. Abnormalities in fatty acid profiles included an apparent elevation in medium chain fatty acids and increased ratios of PL arachidonic to docosahexaenoic acids. Histologically, there was no evidence of fat accumulation in the liver; however, hepatic mitochondria had severe structural abnormalities characteristic of RS. These studies demonstrate that chemical-dependent enhancement of viral virulence is associated with significant alterations of hepatic lipids. We believe that these abnormalities are related to mitochondrial structural damage in RS despite the absence of hepatic steatosis.
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D009981:Influenza B virus; D008055:Lipids / Q000032:analysis*; D008099:Liver / Q000032:analysis*; D051379:Mice; D008815:Mice, Inbred Strains; D009976:Orthomyxoviridae Infections / Q000378:metabolism*; D012202:Reye Syndrome / Q000378:metabolism*; D014280:Triglycerides / Q000032:analysis
D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D014280:Triglycerides