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https://hdl.handle.net/2440/5542
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dc.contributor.author | Rofe, A. | - |
dc.contributor.author | Philcox, J. | - |
dc.contributor.author | Coyle, P. | - |
dc.date.issued | 1996 | - |
dc.identifier.citation | Biochemical Journal, 1996; 31(3):793-797 | - |
dc.identifier.issn | 0264-6021 | - |
dc.identifier.issn | 1470-8728 | - |
dc.identifier.uri | http://hdl.handle.net/2440/5542 | - |
dc.description.abstract | Accumulation of hepatic zinc via metallothionein (MT) induction during infection/inflammation is postulated to benefit a range of metabolic processes. The metabolic consequences of two doses of endotoxin (LPS) (1 and 5 mg/kg, intraperitoneally) were examined in normal (MT+/+) and MT-null (MT-/-) mice (all results means =/- S.E.M., n=6). At 16 h after 1 mg/kg LPS, hypozincaemia was pronounced in the MT+/+ mice (4.4+/-0.2 microM), concomitant with a 36% increase in hepatic Zn and a > 10-fold increase in hepatic MT. Plasma Zn (16.6+/-0.7 microM) and total hepatic Zn were unchanged in MT -/- mice, confirming the importance of MT in altering plasma and hepatic Zn during inflammation. Plasma iron was lower in LPS-treated MT-/- mice, whereas plasma copper increased to a similar extent in both groups of mice. Plasma fibrinogen more than doubled, and was similar in both groups of mice, which questions the importance of MT in acute-phase protein synthesis. Blood and liver glucose concentrations were not significantly different between groups before or after LPS, whereas blood and liver lactate concentrations were significantly lower (31% and 24% respectively) in MT-/- mice after LPS. At 16 h after 5 mg/kg LPS, plasma Zn was decreased even further in MT+/+ mice (2.6+/-0.3 microM), but remained unchanged in MT-/- mice at concentrations significantly above those in 16-h fasted MT-/- mice (15.8+/-0.5 versus 11.3+/-0.3 microM). Total liver Zn was 17% lower than fasting values in MT-/- mice, in contrast with 32% higher in MT+/+ mice. Synthesis of MT (in MT+/+ mice) and fibrinogen in all mice was not further enhanced by the higher LPS dose. Blood glucose was significantly decreased by 18% in MT+/+ mice and by 38% in MT-/- mice after 5 mg/kg LPS. There was a marked 44% decrease in liver glucose in MT-/- mice; that in MT+/+ mice was unchanged from fasting levels, implying a deficit in hepatic gluconeogenesis in LPS-treated MT-/- mice. In the absence of any indication of major hepatotoxicity, the results of this study indicate that energy production, and not acute-phase protein synthesis, may be most influenced by Zn supply during endotoxaemia, suggesting that MT has a role in maintaining hepatic and blood glucose in this metabolic setting. | - |
dc.language.iso | en | - |
dc.publisher | Portland Press Ltd. | - |
dc.source.uri | http://dx.doi.org/10.1042/bj3140793 | - |
dc.subject | Liver | - |
dc.subject | Animals | - |
dc.subject | Mice, Inbred Strains | - |
dc.subject | Mice, Inbred C57BL | - |
dc.subject | Mice, Knockout | - |
dc.subject | Mice | - |
dc.subject | Zinc | - |
dc.subject | Trace Elements | - |
dc.subject | Lipopolysaccharides | - |
dc.subject | Glucose | - |
dc.subject | Blood Glucose | - |
dc.subject | Metallothionein | - |
dc.subject | Crosses, Genetic | - |
dc.subject | Species Specificity | - |
dc.subject | Gluconeogenesis | - |
dc.subject | Dose-Response Relationship, Drug | - |
dc.title | Trace metal, acute phase and metabolic response to endotoxin in metallothionen-null mice | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1042/bj3140793 | - |
pubs.publication-status | Published | - |
Appears in Collections: | Aurora harvest Pathology publications |
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