INTERNATIONAL JOURNAL OF PHARMACOLOGY, cilt.17, sa.2, ss.84-96, 2021 (SCI-Expanded)
Background and Objective: Cytidine-5-diphosphate-choline (CDP-choline) and choline activate the cholinergic anti-inflammatory pathway in case of inflammation. This study investigated the role of CDP-choline and choline along with the contribution of the cyclooxygenase (COX) pathway on the lipopolysaccharide (LPS)-induced endotoxemia model in rats. Materials and Methods: Endotoxemia model was induced by LPS administration. CDP-choline or choline 5 min before and 6 hrs after LPS injection. The sepsis severity, body weight changes, survival rate were evaluated. Serum prostaglandins, Tumour Necrosis Factor (TNF)-alpha, total choline levels were measured. COX-2 mRNA expression and protein levels were analyzed. Spleen tissues were evaluated histomorphological. One-way analysis of variance analysis (ANOVA) or Kruskal Wallis tests was used for statistical analysis. Results: COX-2 expressions in liver and brain tissues, serum prostaglandin E-2, 6-keto prostaglandin F-1 alpha, Thromboxane A(2) and TNF alpha levels were increased 24 hrs after LPS administration. Administrations of CDP-choline or choline were decreased COX-2 expression in the liver. Serum prostaglandin levels were decreased in the CDP-choline-treated group, whereas, only prostaglandin E-2 level was decreased in the choline-treated group. Total choline levels in serum and brain were increased after CDP-choline or choline administration. Accordingly, serum TNF alpha levels and TNF alpha expression in the liver were decreased in CDP-choline and choline-treated groups. TNF alpha expression in the brain was decreased in the choline-treated group, whereas, increased in the CDP-choline-treated group. Conclusion: CDP-choline and choline decreased LPS-induced COX-2 enzyme expression and prostaglandin levels in the periphery by increasing serum and brain total choline levels in the LPS-induced endotoxemia model in rat.