Protective Effects of a Phosphatidylcholine-Enriched Diet in Lipopolysaccharide-Induced Experimental Neuroinflammation in the Rat

Abstract

Our goal was to characterize the neuroprotective properties of orally administered phosphatidylcholine (PC) in a rodent model of systemic inflammation. Sprague-Dawley rats were killed at 3 h, 1 day, 3 days, or 7 days after i.p. administration of lipopolysaccharide (LPS) to determine the plasma levels of tumor necrosis factor α (TNF-α) and interleukin 6 cytokines. The control group and one group of LPS-treated animals were nourished with standard laboratory chow, whereas another LPS-treated group received a special diet enriched with 1% PC for 5 days before the administration of LPS and thereafter during the 7-day observation period. Immunohistochemistry was performed to visualize the bromodeoxyuridine and doublecortin-positive neuroprogenitor cells and Iba1-positive microglia in the hippocampus, whereas the degree of mucosal damage was evaluated on ileal and colon biopsy samples after hematoxylin-eosin staining. The activities of proinflammatory myeloperoxidase and xanthine-oxidoreductase and the tissue nitrite/nitrate (NOx) level were additionally determined, and the cognitive functions were monitored via Morris water maze testing. The inflammatory challenge transiently increased the hippocampal NOx level and led to microglia accumulation and decreased neurogenesis. The intestinal damage, mucosal myeloperoxidase, xanthine-oxidoreductase, and NOx changes were less pronounced, and long-lasting behavioral alterations were not observed. Phosphatidylcholine pretreatment reduced the plasma TNF-α and hippocampal NOx changes and prevented the decreased neurogenesis. These data demonstrated the relative susceptibility of the brain to the consequences of transient peripheral inflammatory stimuli. Phosphatidylcholine supplementation did not reduce the overall extent of peripheral inflammatory activation, but efficiently counteracted the disturbed hippocampal neurogenesis by lowering circulating TNF-α concentrations.

Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine

“…Regardless of its possible abundance in the membranes, liver concentrations of endogenous GPC are significantly depleted after hemorrhagic shock, a prototype of systemic IR injury [7], and previous data suggested us that exogenous GPC may influence the tissue reactions in IR scenarios [12, 13, 31]. Herein, we have outlined a novel route of action for the molecule.…”

Protective Effect of Phosphatidylcholine on Lipopolysaccharide-Induced Acute Inflammation in Multiple Organ Injury

“…Extensive researches up to date suggest that phosphatidylcholine plays a pivotal role in many important areas including maintaining memory and nerve signaling, as a precursor to important neurotransmitters and attenuating acute renal failure and liver dysfunction [17-19]. A number of recent studies have demonstrated an anti-inflammatory potential for PC and its metabolites in various conditions linked to leukocyte activation, including ischemia [20], oxidative stress [21] and endotoxin-induced injuries [22,23]. PUFA, one component of PC, also has been shown to modulate the inflammatory reactions [24,25].…”

Dietary Phosphatidylcholine Supplementation Attenuates Inflammatory Mucosal Damage in a Rat Model of Experimental Colitis

“…Inducible NO synthaseYderived NO has been implicated in several aspects of the inflammatory cascade in experimental or clinical colitis. We earlier reported that PC treatment inhibited the expression and activity of iNOS isoenzyme in vivo (5, 6) and decreased GI tissue NO x levels in endotoxemic rats (9), and in the present study, PC supplementation significantly decreased the stable end product of NO in the colon tissue in both phases of colitis.…”

“…The activity of MPO as a marker of tissue leukocyte infiltration was measured on the pellet of the homogenate (9). Briefly, the pellet was resuspended in K 3 PO 4 buffer (0.05 M; pH 6.0) containing 0.5% hexa-1,6-bisdecyltriethylammonium bromide.…”

“…The XOR activity was determined in the ultrafiltered, concentrated supernatant by a fluorometric kinetic assay based on the conversion of pterine to isoxanthopterine in the presence (total XOR) or absence (xanthine oxidase activity) of the electron acceptor methylene blue (9).…”