Arachidonic Acid Metabolism and HETEs-PGs Imbalance in L. infantum Infection: Implications for Visceral Leishmaniasis Progression

利什曼原虫感染中花生四烯酸代谢和HETEs-PGs失衡:对内脏利什曼病进展的影响

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Abstract

Visceral leishmaniasis (VL) alters lipid metabolism, impacting the production of bioactive compounds like eicosanoids, which regulate inflammationa key aspect of the disease. This study investigated eicosanoid production in Golden Syrian hamsters infected with Leishmania infantum for five months. The infected animals developed splenomegaly, increased creatinine, elevated liver transaminases, granulomas, white pulp hypoplasia, and portal infiltrates. Arachidonic acid (AA) mobilization was elevated in the spleen and liver but unchanged in plasma. Liquid chromatography mass spectrometry (LC-MS/MS) analysis revealed increased hydroxyeicosatetraenoic acids (HETEs) in the spleen, while prostaglandin (PG) E(2), 2-keto-PGE(2), and PGD(2) were reduced. Notably, splenomegaly, higher HETEs, and lower PGs levels correlated with parasite load, suggesting L. infantum manipulates these mediators to promote inflammation and its persistence. The imbalance between HETEs and PGs seems crucial for VL progression, highlighting the need for further research into the mechanisms driving disease pathogenesis.

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