Effects of Various Antioxidants on Endotoxin-Induced Lung Injury and Gene Expression: mRNA Expressions of MnSOD, Interleukin-1β and iNOS

Nan-Hsiung Feng; Shi-Jye Chu; David Wang; Kang Hsu; Chun-Hsiu Lin; Hen-I Lin

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P111 - 120

医药卫生 > 基础医学

DOI： 10.4077/CJP

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Effects of Various Antioxidants on Endotoxin-Induced Lung Injury and Gene Expression: mRNA Expressions of MnSOD, Interleukin-1β and iNOS

Nan-Hsiung Feng ； Shi-Jye Chu ； David Wang ； Kang Hsu ； Chun-Hsiu Lin ； Hen-I Lin

The Chinese Journal of Physiology ； 47 卷 3 期 (2004 / 09 / 30) ， P111 - 120

英文

lung injury ； lipopolysaccharide ； interleukin-1β ； manganese superoxide dismutase ； catalase ； inducible nitric oxide synthase ； oxygen radicals ； antioxidants ； vitamin C

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摘要 │ 参考文献 (36) │ 被引用文献 (1) │ 国际计量

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Antioxidants have been shown to be effective in attenuating acute lung injury. In this study, we determine the effects of various antioxidants by different mechanisms on the lipopolysaccharide (LPS)-induced changes. LPS was administered intravenously at a dose of 10 mg/kg to anesthetized rats. LPS induced a significant decrease in blood pressure (P＜0.01) and increased exhaled nitric oxide (NO) from 3.60±0.18 to 35.53±3.23 ppb (P＜0.01) during an observation period of 4 b. Plasma nitrate concentrations also increased from 0.61±0.06 to 1.54 ±0.22 μmol/l (P＜0.05). LPS-induced oxygen radical release from white blood cells isolated from rat peripheral blood also increased significantly (P＜0.001). After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-1β(IL-1β) and manganese superoxide dismutase (MnSOD). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1β, TNF-α and MnSOD were absent. Four hours after LPS administration, mRNA expressions of iNOS, IL-1, and MnSOD were significantly enhanced, but TNF-αwas not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial cell damage and interstitial edema. Various antioxidants were given 1h after LPS administration. These agents include SOD, catalase (CAT), SOD+CAT or vitamin C (ascorbic acid). These antioxidants effectively reversed the systemic hypotension, reduced the quantity of exhaled NO and plasma nitrate concentration, and prevented acute lung injury. Administration of various antioxidants also significantly attenuated LPS. induced oxygen radical release by rat white blood cells. EPS induced mRNA expressions of MnSOD and iNOS were significantly depressed by these antioxidants. However, only SOD+CAT and vitamin C inhibited the mRNA expression of IL-1β. These results suggest that oxygen radicals are responsible for LPS-induced lung injury. Antioxidants can attenuate the lung injury by inhibiting mRNA expressions of iNOS and IL-1β.

参考文献 ( 36 ) 〈TOP〉

Bagby, G.J.,Plessala, K.J.,Wilson, L.A.,Thompson, J.J.,Nelson, S.(1991).Divergent efficacy of antibody to tumor necrosis factor-alpha in intravascular and peritonitis models of sepsis.J. Infect. Dis.,163,83-88.
Barnes, P.J.(1997).Nuclear factor-kB.Int. J. Biochem. Cell Biol.,29,867-870.
Blackwell, T.S.,Blackwell, T.R.,Holden, E.P.,Christman, B.W.,Christman, J.W.(1996).In viva antioxidant treatment suppresses nuclear factor-kB activation and neutrophilic lung inflammation.J Immunol.,157,1630-1637.
Cadenas, S.,Cadenas, A.M.(2002).Fighting the stranger-antioxidant protection against endotoxicity.Toxicology,180,45-63.
Cadenas, S.,Rojas, C.,Barja, G.(1998).Endotoxin increases oxidative injury to proteins in guinea pig liver: protection by dietary vitamin.C. Pharmacol. Toxicol.,82,11-18.

被引用文献 ( 1 ) 〈TOP〉

Yang, Victoria-Hui,Shen, Amy-Ru,Liou, Teh-Ling,Lee, Chia-Wei,Hwu, Chii-Min,Huang, Zih-Ling,Chien, Eileen Jea,Chien, Chau-Heng(2006).Inducible Nitric Oxide Synthase Expression and Plasma Bilirubin Changes in Rats under Intermittent Hypoxia Treatment.Chinese Journal of Physiology,49(5),275-280.

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