Effects of CDP-Choline and Choline on Gastrointestinal Inflammatory and Monoaminergic Responses in an LPS-Induced Rat Endotoxemia Model

Objectives: Endotoxemia is associated with pronounced gastrointestinal (GI) inflammatory responses and disruption of local neurochemical regulation. Although cytidine-5′-diphosphocholine (CDP-choline) and choline exert anti-inflammatory effects, their region-specific actions on GI inflammation and monoaminergic alterations during endotoxemia remain poorly characterized. Methods: Acute endotoxemia was induced in female Sprague–Dawley rats by intraperitoneal lipopolysaccharide (LPS; 10 mg/kg). Endotoxemia severity was assessed using a standardized sepsis scoring system at 6 and 24 h. GI tissues (esophagus, stomach, duodenum, cecum, and colon) were analyzed for tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), choline acetyltransferase (ChAT), serotonin (5-HT), dopamine (DA), and norepinephrine (NE) by ELISA, alongside histopathological evaluation. Results: LPS significantly elevated sepsis scores, cytokine levels, and monoamine concentrations across all GI regions, with the most pronounced cytokine responses in the duodenum, cecum, and esophagus. CDP-choline attenuated TNF-α and IL-6 elevations more effectively than choline; markedly increased ChAT levels, especially in the esophagus, cecum, and colon; and reduced LPS-induced 5-HT and DA elevations in a region-dependent manner. NE responses were heterogeneous across regions. Histopathologically, CDP-choline largely preserved normal tissue architecture throughout the GI tract, whereas choline provided only partial protection in intestinal tissues. Conclusions: CDP-choline exerted stronger modulatory effects than choline on region-specific GI inflammatory, cholinergic, and monoaminergic responses during acute endotoxemia, supporting further investigation of cholinergic precursors as modulators of GI neuroimmune dysfunction in systemic inflammation.