OBJECTIVES: We investigated whether naloxone could reduce macrophage activation and influence atherosclerotic lesion formation in mice. BACKGROUND: Macrophages play an important role in the inflammatory process in atherosclerosis. Naloxone could inhibit activation of microglia, the resident macrophage in the nervous system. METHODS: The anti-inflammatory effect of naloxone was evaluated by stimulating the macrophage cell culture and FVB mice with lipopolysaccharide or oxidized low-density lipoprotein with and without naloxone pretreatment. Apolipoprotein-E (apoE)-deficient mice received naloxone injection for 10 weeks, and the severity of aortic atherosclerosis was measured. The left common carotid arteries of C57BL/6 mice were ligated near the carotid bifurcation. The mice then received naloxone injection for 4 weeks after ligation, and the severity of neointima formation was evaluated. RESULTS: Naloxone pretreatment significantly suppressed the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6, monocyte chemoattractant protein-1, and superoxide in macrophages after stimulation. In FVB mice, naloxone reduced the TNF-alpha level in circulation, inflammatory cell infiltration in lungs, and superoxide production in aorta. Naloxone injection significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and carotid neointima formation in the C57BL/6 mice after ligation. CONCLUSIONS: Naloxone, with its novel anti-inflammatory effect, significantly reduces atherosclerosis and neointima formation in mice.
OBJECTIVES: We investigated whether naloxone could reduce macrophage activation and influence atherosclerotic lesion formation in mice. BACKGROUND: Macrophages play an important role in the inflammatory process in atherosclerosis. Naloxone could inhibit activation of microglia, the resident macrophage in the nervous system. METHODS: The anti-inflammatory effect of naloxone was evaluated by stimulating the macrophage cell culture and FVB mice with lipopolysaccharide or oxidized low-density lipoprotein with and without naloxone pretreatment. Apolipoprotein-E (apoE)-deficient mice received naloxone injection for 10 weeks, and the severity of aortic atherosclerosis was measured. The left common carotid arteries of C57BL/6 mice were ligated near the carotid bifurcation. The mice then received naloxone injection for 4 weeks after ligation, and the severity of neointima formation was evaluated. RESULTS:Naloxone pretreatment significantly suppressed the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6, monocyte chemoattractant protein-1, and superoxide in macrophages after stimulation. In FVB mice, naloxone reduced the TNF-alpha level in circulation, inflammatory cell infiltration in lungs, and superoxide production in aorta. Naloxone injection significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and carotid neointima formation in the C57BL/6 mice after ligation. CONCLUSIONS:Naloxone, with its novel anti-inflammatory effect, significantly reduces atherosclerosis and neointima formation in mice.
Authors: Ryan Bachtell; Mark R Hutchinson; Xiaohui Wang; Kenner C Rice; Steven F Maier; Linda R Watkins Journal: CNS Neurol Disord Drug Targets Date: 2015 Impact factor: 4.388
Authors: Mark R Hutchinson; Yingning Zhang; Mitesh Shridhar; John H Evans; Madison M Buchanan; Tina X Zhao; Peter F Slivka; Benjamen D Coats; Niloofar Rezvani; Julie Wieseler; Travis S Hughes; Kyle E Landgraf; Stefanie Chan; Stephanie Fong; Simon Phipps; Joseph J Falke; Leslie A Leinwand; Steven F Maier; Hang Yin; Kenner C Rice; Linda R Watkins Journal: Brain Behav Immun Date: 2009-08-11 Impact factor: 7.217
Authors: Sally Bendiks; Debbie M Cheng; Elena Blokhina; Marina Vetrova; Elena Verbitskaya; Natalia Gnatienko; Kendall Bryant; Evgeny Krupitsky; Jeffrey H Samet; Judith I Tsui Journal: AIDS Care Date: 2021-03-07