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• W1991230879 abstract "Oxidative stress during sepsis induces tissue damage, leading to organ dysfunction and high mortality. The antioxidant effects of vitamin E have been reported in several diseases, but not in sepsis. Statins have cholesterol-independent anti-inflammatory effects that are related to a decrease of isoprenoid proteins and oxidative stress. Therefore, we evaluated superoxide anion (O2°−) production and ex vivo effects of vitamin E and simvastatin in sepsis. Fourteen healthy volunteers, 14 intensive care unit (ICU) nonseptic, and 14 ICU patients with sepsis were included in this prospective study. Plasma cholesterol, triglyceride, and vitamin E levels were determined by routine laboratory tests. Superoxide anion production was measured in the venous blood by chemiluminescence technique after phorbol myristate acetate stimulation. Effects of vitamin E and simvastatin on O2°− production was investigated ex vivo. Luminescence was indexed to the leukocyte count. We also investigated the in vitro effect of simvastatin on translocation of NADPH oxidase p21 Rac2 subunit in THP-1 monocytic cell line. The ratio of vitamin E/cholesterol + triglycerides was significantly decreased in septic as compared with nonseptic patients and volunteers. The O2°− production was significantly higher in the group of septic patients than in the others, regardless of the polymorphonuclear leukocyte count. Vitamin E and simvastatin induced ex vivo an inhibition of O2°− production of 20% and 40% respectively. In vitro, simvastatin inhibited phorbol myristate acetate-induced- O2°− production by monocytes through NADPH oxidase inactivation. We conclude that sepsis is associated with a significant decrease in vitamin E and an overproduction of O2°−. Vitamin E and simvastatin lessen this phenomenon through NADPH oxidase inactivation." @default.
• W1991230879 created "2016-06-24" @default.
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• W1991230879 date "2004-07-01" @default.
• W1991230879 modified "2023-09-23" @default.
• W1991230879 title "SUPEROXIDE ANION OVERPRODUCTION IN SEPSIS: EFFECTS OF VITAMIN E AND SIMVASTATIN" @default.
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• W1991230879 doi "https://doi.org/10.1097/01.shk.0000129197.46212.7e" @default.
• W1991230879 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15201699" @default.
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