title: Experimental study on Reye's syndrome: inhibitory effect of interferon alfa on acetylsalicylate-induced injury to rat liver mitochondria.
abstract: Viral infection and acetylsalicylate (ASA)-induced mitochondrial aberration have been reported to play important roles in the pathogenesis of Reye's syndrome. We report that increasing amounts of ASA (0 to 250 mumol/L) resulted in increases in state 4 respiration and decreases in state 3 respiration in rat liver mitochondria in vitro when using alpha-ketoglutarate and/or beta-hydroxybutyrate as respiratory substrates, but not when using succinate as substrate. Interferon alfa (IFN-alpha) (1.5 to 5 x 10(4)IU/mL, approximately 1/100 the therapeutic dosage for humans) and interleukin-1 (IL-1) (1.5 to 2 x 10(4)IU/mL, nearly equivalent to the therapeutic dosage) decreased the severity of the above effects via interaction with mitochondrial membranes. Interferon gamma (IFN-gamma) and interleukin-2 (IL-2) had no such protective effect. Electron microscopic observation indicated that IFN-alpha prevented the induction of mitochondrial swelling by ASA. These results suggest that IFN-alpha may prove to be effective for the treatment of Reye's syndrome.
authors.affiliation: Department of Pediatrics, Kochi Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tomoda
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: T
authors.initials: T
authors.lastname: Kurashige
authors.forename: H
authors.initials: H
authors.lastname: Enzan
authors.forename: M
authors.initials: M
authors.lastname: Miyahara
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D012202:Reye Syndrome / Q000139:chemically induced*
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D001241:Aspirin