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.

Consistency and Accuracy of the Medical Subject Headings® Thesaurus for Electronic Indexing and Retrieval of Chronobiologic References

“…The MeSH heading "circadian rhythm" identified 159 references, but in doing so, it was inaccurate in 13 cases (8.2% of the retrieved references). It improperly identified studies of day/night variations between only two time points in six cases (Bessot et al, 2006;Cui et al, 2005;Kitoh et al, 2005;Nicolas et al, 2005;Pearson & Onambele, 2005;Racinais et al, 2005), seasonal changes in four cases (Haim et al, 2005;Kanikowska et al, 2005;Koch et al, 2006;Tsumura et al, 2005), influences of lunar phases on suicides in one case (Biermann et al, 2005), drug effects on clock genes in one case (Burioka et al, 2005b), and weekly variations in another case (Gruska et al, 2005). On the other hand, four references of studies pertinent to circadian rhythms (2.7% of all circadian studies) were found not to be associated with the MeSH term circadian rhythm (Belanger et al, 2006;Delagrange & Boutin, 2006;Goel et al, 2005;Yanagihara et al, 2006).…”

Evolving roles of circadian rhythms in liver homeostasis and pathology

“…Lipopolysaccharide (LPS) inhibits the ET-1-induced NO production and disrupts liver microcirculation, this process could be blocked by the Rho-kinase (ROCK-2) inhibition in the liver sinusoidal endothelial cells [ 107 ]. In addition, LPS-induced liver injury is greater during the early active than the early resting period, followed by dosing-time-dependent variation in the accumulation of polymorphonuclear cells (PMN) and subsequent IL-6 production [ 108 ]. The PER2 gene is also an important component of liver circadian system and the deficiency of PER2 induces the liver injury and fibrosis during cholestasis [ 96 ].…”

Circadian Clocks and Inflammation: Reciprocal Regulation and Shared Mediators

“…Interestingly, the risk of lethality induced by LPS depends on the time of administration (Halberg et al 1960;Marpegan et al 2009). Rodents treated with LPS late in the rest phase have a much higher risk of mortality than those treated during the active phase, which is correlated to the magnitude of pro-inflammatory cytokines induction (Halberg et al 1960;Kitoh et al 2005;Marpegan et al 2009). In mice, time-of-day dependence was observed for lethality following TNF-a injections (Hrushesky et al 1994) and upon cecal ligation and puncture, an experimental model of sepsis (Silver et al 2012).…”