title: Dosing-time-dependent differences in lipopolysaccharide-induced liver injury in rats.
abstract: Dosing-time-dependent differences in lipopolysaccharide (LPS)-induced liver injury were examined in rats housed under a 12 h light : dark (LD) cycle. LPS (5 mg/kg) was intravenously injected into different groups of rats at 2, 14, or 20 h after light on (HALO). Elevations in serum liver enzymes after 14 HALO were significantly greater than those after 2 HALO. These parameters were lower in rats given LPS at 20 HALO, compared to 14 HALO. The number of polymorphonuclear cells (PMN) in the liver and the amount of hepatic myeloperoxidase activity, which reflects the number of PMN in liver tissues, was significantly greater in the 14 than in the 2 HALO group. In addition, hepatic interleukin-6 (IL-6) production in the 14 HALO group was enhanced compared to that in the 2 HALO trial. These results suggest that LPS-induced liver injury is greater during the early active than during the early resting period. Dosing-time-dependent variation in the accumulation of PMN in the liver and, potentially, subsequent IL-6 production in liver tissues might be involved in this phenomenon.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kitoh
authors.forename: Masami
authors.initials: M
authors.lastname: Ohmori
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Araki
authors.forename: Fujiko
authors.initials: F
authors.lastname: Miyashita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Norio
authors.initials: N
authors.lastname: Sogawa
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002940:Circadian Rhythm; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003624:Darkness; D004334:Drug Administration Schedule; D008027:Light; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase