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Anti-inflammatory and anti-oxidative effects of alpha-lipoic acid in experimentally induced acute otitis media

Published online by Cambridge University Press:  30 May 2016

A Tatar*
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, Ataturk University Medical Faculty, Erzurum, Turkey
M Korkmaz
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, Ordu University Medical Faculty, Turkey
M Yayla
Affiliation:
Department of Pharmacology, Ataturk University Medical Faculty, Erzurum, Turkey
M S Gozeler
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, Ataturk University Medical Faculty, Erzurum, Turkey
V Mutlu
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, Ataturk University Medical Faculty, Erzurum, Turkey
Z Halici
Affiliation:
Department of Pharmacology, Ataturk University Medical Faculty, Erzurum, Turkey
H Uslu
Affiliation:
Department of Microbiology, Ataturk University Medical Faculty, Erzurum, Turkey
H Korkmaz
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, Ordu University Medical Faculty, Turkey
J Selli
Affiliation:
Department of Embryology and Histology, Ataturk University Medical Faculty, Erzurum, Turkey
*
Address for correspondence: Dr Arzu Tatar, Ataturk Uni. Tip Fak., Kulak-Burun-Bogaz AD, 25240-Erzurum, Turkey E-mail: [email protected]

Abstract

Objectives:

To investigate the anti-inflammatory, anti-oxidative and tissue protective effects, as well as the potential therapeutic role, of alpha-lipoic acid in experimentally induced acute otitis media.

Methods:

Twenty-five guinea pigs were assigned to one of five groups: a control (non-otitis) group, and otitis-induced groups treated with saline, penicillin G, alpha-lipoic acid, or alpha-lipoic acid plus penicillin G. Tissue samples were histologically analysed, and oxidative parameters in tissue samples were measured and compared between groups.

Results:

The epithelial integrity was better preserved, and histological signs of inflammation and secretory metaplasia were decreased, in all groups compared to the saline treated otitis group. In the alpha-lipoic acid plus penicillin G treated otitis group, epithelial integrity was well preserved and histological findings of inflammation were significantly decreased compared to the saline, penicillin G and alpha-lipoic acid treated otitis groups. The most favourable oxidative parameters were observed in the control group, followed by the alpha-lipoic acid plus penicillin G treated otitis group.

Conclusion:

Alpha-lipoic acid, with its antioxidant, anti-inflammatory and tissue protective properties, may decrease the clinical sequelae and morbidity associated with acute otitis media.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2016 

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References

1Rettig, E, Tunkel, DE. Contemporary concepts in management of acute otitis media in children. Otolaryngol Clin North Am 2014;47:651–72CrossRefGoogle ScholarPubMed
2Grijalva, CG, Nuorti, JP, Griffin, MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA 2009;302:758–66CrossRefGoogle ScholarPubMed
3Casey, JR, Kaur, R, Friedel, VC, Pichichero, ME. Acute otitis media otopathogens during 2008 to 2010 in Rochester, New York. Pediatr Infect Dis J 2013;32:805–9CrossRefGoogle ScholarPubMed
4Park, SN, Yeo, SW. Effects of antibiotics and steroid on middle ear mucosa in rats with experimental acute otitis media. Acta Otolaryngol 2001;121:808–12Google ScholarPubMed
5Kubba, H, Pearson, JP, Birchall, JP. The aetiology of otitis media with effusion: a review. Clin Otolaryngol Allied Sci 2000;25:181–94CrossRefGoogle ScholarPubMed
6Pichichero, ME. Otitis media. Pediatr Clin North Am 2013;60:391407CrossRefGoogle ScholarPubMed
7Machlin, LJ, Bendich, A. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J 1987;1:441–5CrossRefGoogle ScholarPubMed
8Parks, RR, Huang, CC, Haddad, J Jr.Evidence of oxygen radical injury in experimental otitis media. Laryngoscope 1994;104:1389–92CrossRefGoogle ScholarPubMed
9Takoudes, TG, Haddad, J Jr.Evidence of oxygen free radical damage in human otitis media. Otolaryngol Head Neck Surg 1999;120:638–42CrossRefGoogle ScholarPubMed
10Doner, F, Delibas, N, Dogru, H, Yariktas, M, Demirci, M. The role of free oxygen radicals in experimental otitis media. J Basic Clin Physiol Pharmacol 2002;13:3340CrossRefGoogle ScholarPubMed
11Kawana, M, Kawana, C, Yokoo, T, Quie, PG, Giebink, GS. Oxidative metabolic products released from polymorphonuclear leukocytes in middle ear fluid during experimental pneumococcal otitis media. Infect Immun 1991;59:4084–8CrossRefGoogle ScholarPubMed
12Shay, KP, Moreau, RF, Smith, EJ, Smith, AR, Hagen, TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 2009;1790:1149–60CrossRefGoogle ScholarPubMed
13Packer, L, Kraemer, K, Rimbach, G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17:888–95CrossRefGoogle ScholarPubMed
14Packer, L, Witt, EH, Tritschler, HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19:227–50CrossRefGoogle ScholarPubMed
15Li, G, Fu, J, Zhao, Y, Ji, K, Luan, T, Zang, B. Alpha-lipoic acid exerts anti-inflammatory effects on lipopolysaccharide-stimulated rat mesangial cells via inhibition of nuclear factor kappa B (NF-κB) signaling pathway. Inflammation 2015;38:510–19CrossRefGoogle ScholarPubMed
16Sun, Y, Oberley, LW, Li, Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497500CrossRefGoogle ScholarPubMed
17Sedlak, J, Lindsay, RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 1968;25:192205CrossRefGoogle ScholarPubMed
18Ohkawa, H, Ohishi, H, Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8CrossRefGoogle ScholarPubMed
19Ho, D, Rotenberg, BW, Berkowitz, RG. The relationship between acute mastoiditis and antibiotic use for acute otitis media in children. Arch Otolaryngol Head Neck Surg 2008;134:45–8CrossRefGoogle ScholarPubMed
20Mittal, R, Kodiyan, J, Gerring, R, Mathee, K, Li, JD, Grati, M et al. Role of innate immunity in the pathogenesis of otitis media. Int J Infect Dis 2014;29:259–67CrossRefGoogle ScholarPubMed
21Soares, MP, Gozzelino, R, Weis, S. Tissue damage control in disease tolerance. Trends Immunol 2014;35:483–94CrossRefGoogle ScholarPubMed
22Cayé-Thomasen, P, Tos, M. Histopathologic differences due to bacterial species in acute otitis media. Int J Pediatr Otorhinolaryngol 2002;63:99110CrossRefGoogle ScholarPubMed
23Salomonsen, RL, Hermansson, A, Cayé-Thomasen, P. Ossicular bone modeling in acute otitis media. Otol Neurotol 2010;31:1109–14CrossRefGoogle ScholarPubMed
24MacArthur, CJ, Pillers, DA, Pang, J, Kempton, JB, Trune, DR. Altered expression of middle and inner ear cytokines in mouse otitis media. Laryngoscope 2011;121:365–71CrossRefGoogle ScholarPubMed
25Takoudes, TG, Haddad, J Jr.Free radical production by antibiotic-killed bacteria in the guinea pig middle ear. Laryngoscope 2001;111:283–9CrossRefGoogle ScholarPubMed
26Long, JP, Tong, HH, Shannon, PA, DeMaria, TF. Differential expression of cytokine genes and inducible nitric oxide synthase induced by opacity phenotype variants of Streptococcus pneumoniae during acute otitis media in the rat. Infect Immun 2003;71:5531–40CrossRefGoogle ScholarPubMed
27Yariktas, M, Doner, F, Dogru, H, Yasan, H, Delibas, N. The role of free oxygen radicals on the development of otitis media with effusion. Int J Pediatr Otorhinolaryngol 2004;68:889–94CrossRefGoogle ScholarPubMed
28Wright, CG, Meyerhoff, WL. Pathology of otitis media. Ann Otol Rhinol Laryngol Suppl 1994;163:24–6CrossRefGoogle ScholarPubMed
29Lin, J, Haruta, A, Kawano, H, Ho, SB, Adams, GL, Juhn, SK et al. Induction of mucin gene expression in middle ear of rats by tumor necrosis factor-alpha: potential cause for mucoid otitis media. J Infect Dis 2000;182:882–7CrossRefGoogle ScholarPubMed
30Yao, J, Mackman, N, Edgington, TS, Fan, ST. Lipopolysaccharide induction of the tumor necrosis factor-alpha promoter in human monocytic cells. Regulation by Egr-1, c-Jun, and NF-kappa B transcription factors. J Biol Chem 1997;272:17795–801CrossRefGoogle Scholar
31Barrett, TQ, Kristiansen, LH, Ovesen, T. NF-kappaB in cultivated middle ear epithelium. Int J Pediatr Otorhinolaryngol 2003;67:895903CrossRefGoogle ScholarPubMed
32Christman, JW, Blackwell, TS, Juurlink, BH. Redox regulation of nuclear factor kappa B: therapeutic potential for attenuating inflammatory responses. Brain Pathol 2000;10:153–62CrossRefGoogle ScholarPubMed
33Suzuki, YJ, Aggarwal, BB, Packer, L. Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Biochem Biophys Res Commun 1992;189:1709–15CrossRefGoogle ScholarPubMed
34Kim, HJ, Chang, EJ, Kim, HM, Lee, SB, Kim, HD, Su, Kim G et al. Antioxidant alpha-lipoic acid inhibits osteoclast differentiation by reducing nuclear factor-kappaB DNA binding and prevents in vivo bone resorption induced by receptor activator of nuclear factor-kappaB ligand and tumor necrosis factor-alpha. Free Radic Biol Med 2006;40:1483–93CrossRefGoogle ScholarPubMed
35Conlon, BJ, Aran, JM, Erre, JP, Smith, DW. Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant alpha-lipoic acid. Hear Res 1999;128:40–4CrossRefGoogle ScholarPubMed
36Kim, J, Cho, HJ, Sagong, B, Kim, SJ, Lee, JT, So, HS et al. Alpha-lipoic acid protects against cisplatin-induced ototoxicity via the regulation of MAPKs and proinflammatory cytokines. Biochem Biophys Res Commun 2014;449:183–9CrossRefGoogle ScholarPubMed
37Quaranta, N, Dicorato, A, Matera, V, D'Elia, A, Quaranta, A. The effect of alpha-lipoic acid on temporary threshold shift in humans: a preliminary study. Acta Otorhinolaryngol Ital 2012;32:380–5Google ScholarPubMed
38Tatar, A, Yoruk, O, Unal, D, Selli, J, Yayla, M, Halici, Z. The effect of alpha-lipoic acid on myringosclerosis in a rat model. J Int Adv Otol 2014;10:222–7CrossRefGoogle Scholar
39Eremeeva, ME, Silverman, DJ. Effects of the antioxidant alpha-lipoic acid on human umbilical vein endothelial cells infected with Rickettsia rickettsii. Infect Immun 1998;66:2290–9CrossRefGoogle ScholarPubMed
40Cadirci, E, Altunkaynak, BZ, Halici, Z, Odabasoglu, F, Uyanik, MH, Gundogdu, C et al. Alpha-lipoic acid as a potential target for the treatment of lung injury caused by cecal ligation and puncture-induced sepsis model in rats. Shock 2010;33:479–84CrossRefGoogle ScholarPubMed
41Aladag, I, Guven, M, Eyibilen, A, Sahin, S, Koseoglu, D. Efficacy of vitamin A in experimentally induced acute otitis media. Int J Pediatr Otorhinolaryngol 2007;71:623–8CrossRefGoogle ScholarPubMed
42Aydogan, F, Tastan, E, Aydın, E, Senes, M, Akgedik, S, Berkem, R et al. Antioxidant role of selenium in rats with experimental acute otitis media. Indian J Otolaryngol Head Neck Surg 2013;65:541–7CrossRefGoogle ScholarPubMed