Figure 1.
(A) Study Protocol I. Balb/c mice were included in a 16-week protocol for induction of liver cirrhosis by oral administration of CCl4. A subgroup of animals (six CCl4-treated and four control mice) was subjected to laparotomy at different study weeks to follow progression of fibrosis, inflammation, bactDNA translocation and NE hepatic levels. CCl4: carbon tetrachloride; ig.: intragastrically. (B) Study Protocol II. CCl4-treated Balb/c mice were distributed to receive saline, 6-OHD for sympathetic denervation, Nebivolol for beta-adrenergic receptor (ADRB)-1 blockade, or Butoxamine for ADRB-2 blockade. Within each group, animals were further distributed to receive saline or E. coli-DNA. Laparotomies were performed in all subgroups. CCl4: carbon tetrachloride; ip: intraperitoneally; 6-OHD: 6-hydroxydopamine; sc: subcutaneously;
Table 1.
Characteristics of CCl4-treated mice included in the study at different Stages.
Table 2.
Presence of bactDNA in MLNs and livers of control and CCl4-treated mice at different Stages.
Table 3.
Liver NE, cytokine and ADRB levels in control and CCl4-treated mice in basal and protocol Stages.
Figure 2.
Inflammatory and sympathetic activities in the liver.
(A) Liver levels of NE, TNF-alpha and IL-6 in CCl4-treated mice according to bactDNA translocation into liver. *p<0.05 compared with bactDNA-negative CCl4-treated mice. (B) Correlations between liver NE, TNF-alpha and IL-6 in CCl4-treated mice according to bactDNA translocation into liver. r: Spearman’s rank correlation coefficient in bactDNA+ mice; NE: norepinephrine; bactDNA: bacterial DNA.
Figure 3.
Interaction between inflammatory and sympathetic activities in the liver.
Correlations between ADRB1 levels and NE, TNF-alpha and IL-6 levels in the liver of CCl4-treated mice according to bactDNA translocation. r: Spearman’s rank correlation coefficient in bactDNA+ mice; NE: norepinephrine; ADRB1: beta-1 adrenergic receptor; bactDNA: bacterial DNA.
Figure 4.
Liver inflammatory levels after different treatments.
Levels of TNF-alpha and IL-6 in the liver of mice undergoing different experimental conditions. All mice were pretreated with an intraperitoneal single dose of CCl4 (1uL/g body weight) to generate liver damage. After 2 days, animals were grouped for a 5-day treatment with saline, 6-OHD (200 mg/Kg, intraperitoneal), Nebivolol (5 mg/Kg every 12 h, subcutaneous) or Butoxamine (5 mg/Kg every 12 h, subcutaneous). Then, animals received E. coli DNA (200ng, intraperitoneal). A subgroup of animals remained without E. coli DNA injection as controls. *p<0,05 compared with all E. coli DNA-negative conditions; #p<0,05 compared with the rest of conditions, except Nevibolol+/E. coli DNA+; $p<0,05 compared with the rest of conditions, except 6-OHD+/E. coli DNA+; 6-OHD: 6-hydroxidopamine; NE: norepinephrine.
Figure 5.
Integration of different processes along study weeks.
Illustration of the temporal evolution on the interaction between fibrosis, bacterial translocation and pro-inflammatory and sympathetic activities in the experimental model of CCl4-induced liver damage. BT: bacterial translocation; NE: norepinephrine.