pr-39 and Shock--Septic

The lethal effects occurring in neonatal (< 24-h old) BALB/c mice after challenge with E. coli lipopolysaccharide (LPS) were significantly counteracted by pretreatment with antibacterial peptide PR-39. Neonatal mice protection was probably related to the depressive effect of PR-39 on production of TNF-alpha known to be the major mediator of the lethal effects of neonatal endotoxic shock. Indeed, TNF-alpha plasmatic levels were consistently lower in pups pretreated with PR-39 compared with controls. Administration 24 h after challenge was no longer effective. Although PR-39 and anti-TNF-alpha doses were ineffective alone, when combined at different ratios protected neonatal mice. The present experiments show the potential use of peptide PR-39 in preventing neonatal endotoxic shock.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Disease Models, Animal; Escherichia coli; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Shock, Septic; Survival Analysis; Tumor Necrosis Factor-alpha

The effects of the antibacterial peptide PR-39 on nitric oxide (NO) and liver oxygenation (pO(2)) in a mouse model of endotoxaemia have been explored. In vivo electron paramagnetic resonance (EPR) spectroscopy was used to make direct measurements of liver NO and pO(2). Measurements of pO(2) were made at two different anatomical locations within hepatic tissue to assess effects on blood supply (hence oxygen supply) and lobule oxygenation; selectively from the liver sinusoids or an average pO(2) across the liver lobule. PR-39 induced elevated levels of liver NO at 6 h following injection of lipopolysaccharide (LPS) as a result of increased iNOS expression in liver, but had no effect on eNOS or circulatory NO metabolites. Sinusoidal oxygenation was preserved, and pO(2) across the hepatic tissue bed improved with PR-39 treatment. We propose that the beneficial effects of PR-39 on liver in this septic model were mediated by increased levels of local NO and preservation of oxygen supply to the liver sinusoids.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Disease Models, Animal; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxygen; Oxygen Consumption; Regional Blood Flow; Shock, Septic; Time Factors