Effect of Neostigmine on Organ Injury in Murine Endotoxemia: Missing Facts about the Cholinergic Antiinflammatory Pathway

• Published in: World journal of surgery Vol. 29; no. 11; pp. 1483 - 1489
• Main Authors: Akinci, Seda B., Ulu, Nadir, Yondem, Omer Z., Firat, Pinar, Guc, M. Oguz, Kanbak, Meral, Aypar, Ulku
• Format: Journal Article
• Language: English
• Published: New York Springer‐Verlag 01-11-2005; Springer; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Disease Models, Animal; Endotoxemia - drug therapy; Endotoxemia - physiopathology; Escherichia coli Infections - drug therapy; Escherichia coli Infections - pathology; General aspects; Injury Score; Interstitial Inflammation; Kidney - pathology; Liver - pathology; Lung - pathology; Male; Medical sciences; Mice; Mice, Inbred Strains; Neostigmine; Neostigmine - administration & dosage; Neostigmine - pharmacology; Organ Injury; Parasympathomimetics - administration & dosage; Parasympathomimetics - pharmacology; Shock, Septic - drug therapy; Shock, Septic - physiopathology; Spleen - pathology; Vacuolar Degeneration; Medicine; Vertebrata; Mammalia; Treatment; Mouse; Animal; Surgery; Rodentia; Antiinflammatory agent; Lesion; Endotoxemia; Organ
• ISSN: 0364-2313; 1432-2323
• DOI: 10.1007/s00268-005-0073-2

Electrical and pharmacologic stimulation of the efferent cholinergic antiinflammatory pathway suppress the systemic inflammatory response and can prevent lethal endotoxemia. Neostigmine, a cholinergic agent, has not been tested to determine if it can prevent histopathologic organ injury in endotoxemia. In the present study, the effects of neostigmine treatment on the histopathologic organ injury inflicted by Escherichia coli endotoxin in a mouse model of septic shock was investigated. Endotoxemia in mice caused weight loss and increased spleen, liver, and lung weight. When the organs were examined for histopathologic injury, endotoxemia increased interstitial inflammation in the lungs, liver injury, and organ injury in general terms; neostigmine, at a dose of 0.1 mg/kg, failed to attenuate these effects. Although the simultaneous administration of neostigmine at a dose of 0.3 mg/kg and endotoxin decreased interstitial inflammation in the lungs, vacuolar degeneration in the liver, and total liver injury, mortality was increased with this dose in the presence of endotoxemia. We conclude that neostigmine at a dose of 0.1 mg/kg was not protective against histopathologic organ injury in mice with endotoxemia, and a higher dose (0.3 mg/kg) was not tolerated probably owing to nonspecific parasympathetic action including cardiovascular effects. Further studies are required to determine the contribution of sites in the cholinergic antiinflammatory pathway.