Journal List > Tuberc Respir Dis > v.62(2) > 1001050

Huh, Hong, Kim, Lim, and Koh: The Efficacy of α-lipoic Acid on the Endotoxin-induced Acute Lung Injury

Abstract

Background

Oxidative stress may play an important role in the pathogenesis of endotoxin-induced acute lung injury (ALI). This study evaluated the therapeutic effect of α-lipoic acid, a nonenzymatic antioxidant, in a rat model of lipopolysaccharide (LPS) induced ALI.

Materials and Methods

ALI was induced in Sprague-Dawley rats by instilling LPS (E.coli, 3mg/Kg) into the trachea. The rats were classified into the control, control+α-lipoic acid, LPS, and LPS+α-lipoic acid groups.The lung lavage neutrophil count, cytokine-induced neutrophil chemoattractant (CINC), lung myeloperoxidase (MPO), and cytokine concentrations (TNF-α, IL-1β, IL-6 and IL-10) were measured at 2 h and 6 h after LPS administration.

Results

The total cell and neutrophil counts of the LPS+α-lipoic acid groups were significantly lower than the LPS groups. The protein concentration in the BAL fluid was similar in the LPS groups and LPS+α-lipoic acid groups. The TNF-α, IL-1β, and IL-6 concentrations in the BAL fluid were not decreased by the α-lipoic acid treatment in the LPS treated rats.

Conclusions

Although α-lipoic acid decreased the level of LPS-induced neutrophil infiltration into the lung, it could not attenuate the LPS-induced ALI at the dose administered in this study.

Figures and Tables

Figure 1
The effect of α-lipoic acid on the level of CINC of BAL fluid in rats treated with LPS injection (L: LPS group, LA: LPS+α-lipoic acid group) (*p<0.05)
trd-62-105-g001
Figure 2
The effect of α-lipoic acid on the level of MIP of BAL fluid in rats treated with LPS injection (L: LPS, LA: LPS+α-lipoic acid) (*p<0.05)
trd-62-105-g002
Figure 3
The effect of α-lipoic acid on the level of cytokines of BAL fluid in rats treated with LPS (C: control, A: α-lipoic, L: LPS, LA: LPS+α-lipoic acid) (*p<0.05)
trd-62-105-g003
Table 1
Total cell count and neutrophil count in BAL fluid at 2 hour after LPS intratracheal (IT) injection
trd-62-105-i001

*p value; versus Control group, p value; versus LPS group

Table 2
Total cell count and neutrophil count in BAL fluid at 6 hour after LPS injection
trd-62-105-i002

*p value; versus Control group, p value; versus LPS group

Table 3
Lung myeloperoxidase (MPO) after LPS injection
trd-62-105-i003

*p value; versus Control group, p value; versus LPS group

Table 4
Protein concentration in BAL fluid after LPS injection
trd-62-105-i004

*p value; versus Control group, p value; versus LPS group

References

1. Koh Y, Lee YM, Lim CM, Lee SS, Shim TS, Lee SD, et al. Effects of heat pretreatment on histopathology, cytokine production, and surfactant in endotoxin-induced acute lung injury. Inflammation. 2001. 25:187–196.
2. Yang KY, Arcaroli JJ, Abraham E. Early alterations in neutrophil activation are associated with outcome in acute lung injury. Am J Respir Crit Care Med. 2003. 167:1567–1574.
3. Abraham E, Carmody A, Shenkar R, Arcaroli J. Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2000. 279:L1137–L1145.
4. Chignard M, Balloy V. Neutrophil recruitment and increased permeability during acute lung injury induced by lipopolysaccharide. Am J Physiol Lung Cell Mol Physiol. 2000. 279:L1083–L1090.
5. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med. 1989. 320:365–376.
6. Chow CW, Herrera Abreu MT, Suzuki T, Downey GP. Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol. 2003. 29:427–431.
7. Packer L. alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kappa B signal transduction and protects against oxidative injury. Drug Metab Rev. 1998. 30:245–275.
8. Cao X, Phillis JW. The free radical scavenger, alpha-lipoic acid, protects against cerebral ischemia-reperfusion injury in gerbils. Free Radic Res. 1995. 23:365–370.
9. van Dam PS. Oxidative stress and diabetic neuropathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev. 2002. 18:176–184.
10. Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003. 26:770–776.
11. Suntres ZE. Prophylaxis against lipopolysaccharide-induced liver injuries by lipoic acid in rats. Pharmacol Res. 2003. 48:585–591.
12. Blackwell TS, Blackwell TR, Holden EP, Christman BW, Christman JW. In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation. J Immunol. 1996. 157:1630–1637.
13. Rocksen D, Ekstrand-Hammarstrom B, Johansson L, Bucht A. Vitamin E reduces transendothelial migration of neutrophils and prevents lung injury in endotoxin-induced airway inflammation. Am J Respir Cell Mol Biol. 2003. 28:199–207.
14. Islam KN, Devaraj S, Jialal I. alpha-Tocopherol enrichment of monocytes decreases agonist-induced adhesion to human endothelial cells. Circulation. 1998. 98:2255–2261.
15. Ortolani O, Conti A, De Gaudio AR, Masoni M, Novelli G. Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome. Shock. 2000. 13:14–18.
16. Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995. 19:227–250.
17. Moini H, Packer L, Saris NE. Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol. 2002. 182:84–90.
18. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002. 23:599–622.
19. Antonicelli F, Brown D, Parmentier M, Drost EM, Hirani N, Rahman I, et al. Regulation of LPS-mediated inflammation in vivo and in vitro by the thiol antioxidant Nacystelyn. Am J Physiol Lung Cell Mol Physiol. 2004. 286:L1319–L1327.
20. Serrano CV Jr, Mikhail EA, Wang P, Noble B, Kuppusamy P, Zweier JL. Superoxide and hydrogen peroxide induce CD18-mediated adhesion in the postischemic heart. Biochim Biophys Acta. 1996. 1316:191–202.
21. Zaluska WT, Ksiazek A, Roliski J. Effect of vitamin E modified cellulose membrane on human lymphocyte, monocyte, and granulocyte CD11b/CD18 adhesion molecule expression during hemodialysis. ASAIO J. 2001. 47:619–622.
22. Nitto T, Araki Y, Takeda Y, Sendo F. Pharmacological analysis for mechanisms of GPI-80 release from tumour necrosis factor-alpha-stimulated human neutrophils. Br J Pharmacol. 2002. 137:353–360.
23. Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Moller W, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Free Radic Res. 1999. 31:171–179.
24. Bhatti F, Mankhey RW, Asico L, Quinn MT, Welch WJ, Maric C. Mechanisms of antioxidant and pro-oxidant effects of alpha-lipoic acid in the diabetic and nondiabetic kidney. Kidney Int. 2005. 67:1371–1380.
25. Meduri GU, Kohler G, Headley S, Tolley E, Stentz F, Postlethwaite A. Inflammatory cytokines in the BAL of patients with ARDS: persistent elevation over time predicts poor outcome. Chest. 1995. 108:1303–1314.
26. Goodman RB, Strieter RM, Martin DP, Steinberg KP, Milberg JA, Maunder RJ, et al. Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1996. 154:602–611.
TOOLS
Similar articles