Figure 1

Extracellular ATP signaling enhances APAP-induced hepatotoxicity. (A) Liver intravital microscopy showing sinusoids (in red) and GFP-expressing neutrophils (in green). Mice were treated with acetaminophen (500 mg/Kg; 24 h) and a group received apyrase (25 U/mice) 2 hours after APAP treatment. Control mice were wild type C57 or Lysm-eGFP (in intravital microscopy studies). No significant differences regarding liver injury were observed between C57 and C57-Lysm-eGFP expressing mice. Note the reduced liver injury and neutrophil recruitment in apyrase-treated mice. (B) H&E stained liver sections confirmed liver injury and partial protection promoted by extracellular ATP metabolism by apyrase. (C) Circulating levels of liver transaminase (ALT) and (D-E) pro-inflammatory cytokines (TNF-α and IL-1β). (F) Serum ALT levels of APAP-challenged mice treated with different purinergic receptors antagonists TNP-ATP (selective P2X, 1 mg/Kg) and oxi-ATP (selective P2X7, 9 mg/Kg). * P < 0.05 in comparison to control group and ** in comparison to vehicle-treated group. N = 5/group. Data are mean ± SEM. Scale: 100 μm.