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Glycyrrhizin protects against porcine endotoxemia through modulation of systemic inflammatory response.

Wang W, Zhao F, Fang Y, Li X, Shen L, Cao T, Zhu H - Crit Care (2013)

Bottom Line: However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response.By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Glycyrrhizin (GL) was recently found to suppress high-mobility group box 1 (HMGB1)-induced injury by binding directly to it. However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.

Methods: Twenty-one pigs were divided into four groups: sham group (n=3), control group (n=6), ethyl pyruvate group (n=6) and glycyrrhizin group (n=6). Pigs were anesthetized, mechanically ventilated, monitored and given a continuous intravenous infusion of lipopolysaccharide (LPS). Twelve hours after the start of the LPS infusion, ethyl pyruvate (30 mg/kg/hr) or glycyrrhizin (1 mg/kg/hr) was administered for 12 hours. Systemic and pulmonary hemodynamics, oxygen exchange, and metabolic status were measured. The concentrations of cytokines in serum and the corresponding gene and protein expressions in tissue samples from liver, lungs, kidneys, small intestine and lymph nodes were measured.

Results: GL maintained the stability of systemic hemodynamics and improved pulmonary oxygen exchange and metabolic status. GL also attenuated organ injury and decreased the serum levels of HMGB1 and other pro-inflammatory cytokines by inhibiting their gene and protein expression.

Conclusions: GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response. By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

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Protein expression of HMGB1, NF-κB p65, IL-6 and IL-10. A) Western-blot showed the expression levels of HMGB1, NF-κB p65 (NF-κB), IL-6 and IL-10 in lung, liver, kidney, intestine and lymph node. The expression of NF-κB p65 was detected using nuclear protein while others were detected using total protein. B) Quantitative assessment of protein relative to β-actin. * P < 0.05 versus control group. HMBG1, high-mobility group box 1; NK-κB, nuclear factor-kappaB.
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Figure 7: Protein expression of HMGB1, NF-κB p65, IL-6 and IL-10. A) Western-blot showed the expression levels of HMGB1, NF-κB p65 (NF-κB), IL-6 and IL-10 in lung, liver, kidney, intestine and lymph node. The expression of NF-κB p65 was detected using nuclear protein while others were detected using total protein. B) Quantitative assessment of protein relative to β-actin. * P < 0.05 versus control group. HMBG1, high-mobility group box 1; NK-κB, nuclear factor-kappaB.

Mentions: As shown in Figures 6 and 7, expression levels of HMGB1 mRNA and protein in lungs, liver, kidneys, small intestine and lymph node were enhanced markedly after endotoxemia compared with the sham group. Treatment with GL or EP reduced expression levels of HMGB1 mRNA and protein in the five organs, especially in the lung and small intestine compared with the con group. Endotoxemia also up-regulated the expression of NF-κB p65 mRNA and increased activated protein of NF-κB p65 in the five organs compared with the sham group. The levels of NF-κB p65 mRNA and activated protein in most of the organs were markedly lower in the GL or EP group than the con group.


Glycyrrhizin protects against porcine endotoxemia through modulation of systemic inflammatory response.

Wang W, Zhao F, Fang Y, Li X, Shen L, Cao T, Zhu H - Crit Care (2013)

Protein expression of HMGB1, NF-κB p65, IL-6 and IL-10. A) Western-blot showed the expression levels of HMGB1, NF-κB p65 (NF-κB), IL-6 and IL-10 in lung, liver, kidney, intestine and lymph node. The expression of NF-κB p65 was detected using nuclear protein while others were detected using total protein. B) Quantitative assessment of protein relative to β-actin. * P < 0.05 versus control group. HMBG1, high-mobility group box 1; NK-κB, nuclear factor-kappaB.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672474&req=5

Figure 7: Protein expression of HMGB1, NF-κB p65, IL-6 and IL-10. A) Western-blot showed the expression levels of HMGB1, NF-κB p65 (NF-κB), IL-6 and IL-10 in lung, liver, kidney, intestine and lymph node. The expression of NF-κB p65 was detected using nuclear protein while others were detected using total protein. B) Quantitative assessment of protein relative to β-actin. * P < 0.05 versus control group. HMBG1, high-mobility group box 1; NK-κB, nuclear factor-kappaB.
Mentions: As shown in Figures 6 and 7, expression levels of HMGB1 mRNA and protein in lungs, liver, kidneys, small intestine and lymph node were enhanced markedly after endotoxemia compared with the sham group. Treatment with GL or EP reduced expression levels of HMGB1 mRNA and protein in the five organs, especially in the lung and small intestine compared with the con group. Endotoxemia also up-regulated the expression of NF-κB p65 mRNA and increased activated protein of NF-κB p65 in the five organs compared with the sham group. The levels of NF-κB p65 mRNA and activated protein in most of the organs were markedly lower in the GL or EP group than the con group.

Bottom Line: However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response.By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Glycyrrhizin (GL) was recently found to suppress high-mobility group box 1 (HMGB1)-induced injury by binding directly to it. However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.

Methods: Twenty-one pigs were divided into four groups: sham group (n=3), control group (n=6), ethyl pyruvate group (n=6) and glycyrrhizin group (n=6). Pigs were anesthetized, mechanically ventilated, monitored and given a continuous intravenous infusion of lipopolysaccharide (LPS). Twelve hours after the start of the LPS infusion, ethyl pyruvate (30 mg/kg/hr) or glycyrrhizin (1 mg/kg/hr) was administered for 12 hours. Systemic and pulmonary hemodynamics, oxygen exchange, and metabolic status were measured. The concentrations of cytokines in serum and the corresponding gene and protein expressions in tissue samples from liver, lungs, kidneys, small intestine and lymph nodes were measured.

Results: GL maintained the stability of systemic hemodynamics and improved pulmonary oxygen exchange and metabolic status. GL also attenuated organ injury and decreased the serum levels of HMGB1 and other pro-inflammatory cytokines by inhibiting their gene and protein expression.

Conclusions: GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response. By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

Show MeSH
Related in: MedlinePlus