title: Interactions between U-937 human macrophages and tyloxapol.
abstract: Tyloxapol is reported to prevent macrophages from reacting to endotoxin. However, the intracellular responses that tyloxapol induces in macrophages are still not fully explored. Hence, the objective of this study was to evaluate the intracellular events in macrophages treated with tyloxapol and assess the antioxidant properties of tyloxapol in endotoxin-activated macrophages. Using flow cytometry, we examined intracellular responses in macrophages: reactive oxygen species (ROS) content, mitochondria membrane potential, and cell cycle profiles. We also assessed the antioxidant properties of tyloxapol in endotoxin-activated macrophages. Kinetic hydrogen peroxide production tended to decline with increasing doses. Tyloxapol produced a progressive increase followed by a decline in superoxide anion production in macrophages with increasing doses. Tyloxapol also caused unstable fluctuations in mitochondrial membrane potential. Apoptosis had developed at higher doses after 4h of incubation time. After 2h of tyloxapol-pretreatment, tyloxapol acted as an antioxidant only at lower doses. Most tyloxapol-pretreated cells at lower doses fully recovered from the changes in superoxide anion and hydrogen peroxide production. Our findings contribute to a better understanding of the molecular action of tyloxapol in macrophages and how it protects macrophages against endotoxin.
authors.affiliation: Graduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, 60 Erh-Jen Road, Sec. 1, Jen-Te, Tainan 717, Taiwan. kuojunghua@yahoo.com.tw
authors.forename: Jung-Hua Steven
authors.initials: JH
authors.lastname: Kuo
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Lin
authors.forename: Jo-Wen
authors.initials: JW
authors.lastname: Tseng
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005562:Formazans / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007202:Indicators and Reagents / Q000378:metabolism; D008081:Liposomes / Q000494:pharmacology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology; D010088:Oxidoreductases / Q000032:analysis; D011092:Polyethylene Glycols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D005562:Formazans; D007202:Indicators and Reagents; D008081:Liposomes; D017382:Reactive Oxygen Species; D013481:Superoxides; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C016811:tyloxapol