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There is evidence that mitochondrial dysfunction plays a role in sepsis-related tissue damage. Several studies described the uptake and endocytosis of lipopolysaccharide (LPS) by various cells. LPS has been localized in different parts of the cytoplasm, including at close proximity to or within mitochondria . Whether effects of LPS on mitochondrial respiration are time and/or dose dependent is unknown.
Quadriceps muscle biopsy was taken from seven anaesthetized pigs. Mitochondria were isolated using differential centrifugation and immediately incubated with 0.1, 1, 10, 50 and 100 μg LPS per mg mitochondria protein on ice for 2 and 4 hours. Respiration rates were determined polarographically using glutamate and succinate as substrates to test the function of complex I and II. Respiration Control Ratio (State 3/State 4) was derived for each substrate. Repeated-measures ANOVA was used to analyze time and dose effect of LPS on respiration rates.
In vitro, LPS has time-dependent and dose-dependent effects on muscle mitochondrial respiration. This has consequences for design and interpretation of experimental studies.