Ratlarda Deneyse Olarak Oluşturulan İnfilamasyonla İlişkili Timpanoskleroza Alfa Lipoik Asidin Etkisi

Abstract

Amaç: Timpanoskleroz timpanik membran ve orta kulak mukozasının sklerotik ve hiyalinize değişikliği ile giden anormal bir doku reaksiyonudur. Bir antioksidan olan alfa lipoik asidin, inflamasyonla ile ilişkili timpanosklerozda basit ve etkili bir tedavi biçimini temsil edebileceğini varsaydık. Çalışmanın amacı, alfa lipoik asidin sıçanlarda deneysel olarak indüklenen infilamasyon ile ilşkili timpanoskleroz üzerindeki etkilerini araştırmaktı.
Materyal Metod: Çalışmamızda 20 adet Wistar albino sıçan kullanıldı. Sıçanlar rastgele olarak onarlı iki gruba ayrıldı. 1. gruba ALA 50 mg/kg yedi gün boyunca günde bir defa intraperitoneal uygulandı. 2. gruba salin aynı miktarda yedi gün boyunca günde bir defa intraperitoneal uygulandı. Histopatolojik olarak değerlendirmemizde inflamasyon, fibrozis ve lamina propria kalınlığı değerlendirildi.
Bulgular: Orta kulakta enflamasyon, fibrozis ve timpanik membran lamina propria kalınlığı değerlendirildiğinde, çalışma grubunda kontrol gurubuna göre daha az olduğu değerlendirildi.
Sonuç: Antiokstidan özellik gösteren alfa lipoik asit’in deneysel olarak oluşturulmuş inflamasyonla ile ilişkili timpanosklerozu önleyebileceği görüldü.

Keywords

• Alfa-Lipoik asit,inflamasyon,fibroz

The Application of Lipoic Acid in Experimentally Induced Tympanosclerosis in Rats

Abstract

Abstract

Background/Aims:Tympanosclerosis is an abnormal tissue reaction resulting in sclerotic and hyalinization changes in the tympanic membrane and middle ear.  We hypothesized that alpha lipoic acid, an antioxidant, may represent a simple and effective form of treatment in inflammattion-related tympanosclerosis. The purpose of the study was to investigate the effects of alpha lipoic acid on experimentally induced inflammattion-related tympanosclerosis in rats.

Methods:Twenty albino Wistar rats were randomly divided into two equal groups. The first (study) group was administered 50 mg/kg alpha lipoic acid by the intraperitoneal route once daily for 7 days. The second group was administered the same saline solution intraperitoneally once daily for 7 days. Inflammation, fibrosis and lamina propria thickness were assessed at the subsequent histopathological examination.

Results:In the study group, significantly less middle ear inflammation and fibrosis developed and the tympanic membrane lamina propria was thinner compared to the control group. 

Conclusions: Alpha lipoic acid was found capable of preventing experimentally induced inflammattion-related tympanosclerosis with its antioxidant characteristics.

Keywords

• alpha lipoic acid,inflammation,fibrosis,fibrosis

References

1. 1. Pulec JL, Deguine C. Long-term ventilating tube with tympanosclerosis. Ear Nose Throat J. 2000; 79: 680. 2. Koç A, Uneri C. Genetic predisposition for tympanosclerotic degeneration. Eur Arch Otorhinolaryngol. 2002 ;259: 180-3. 3. Karlidag T, Ilhan N, Kaygusuz I, Keles E, Yalcin S. Comparisson of free radicals and antioxidant enzymes in chronic otitis media with and without tympanosclerosis. Laryngoscope 2004; 114: 85-9. 4. Mattsson C, Magnusson K, Hellstrom S. Myringosclerosis caused by increased oxygen concentration in traumatized tympanic membranes, experimental study. Ann Otol Rhinol Laryngol 1995; 104: 625-32. 5. Han D, Handelman G, Marcocci L, Sen CK, Roy S, Kobuchi H et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors. 1997; 6: 321-38.6. Moini H, Packer L, Saris NE. Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol. Appl. Pharmacol. 2002; 182: 84-90. 7. Packer L, Witt EH, Tritschler HJ. α-Lipoic acid as a biological antioxidant. Free Radic. Biol. Med. 1995; 19: 227–50. 8. Toklu HZ, Hakan T, Celik H, Biber N, Erzik C, Ogunc AV, et al. Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats. J Spinal Cord Med. 2010; 33(4): 401-9. 9. Forse´ni M, Bagger-Sjöback D, HultcrantzM. A study of ınflamatory mediators in the human tympanosclerotic middle ear. Arch Otolaryngol Head Neck Surg. 2001; 127: 559-64. 10. Morgan WC. Tympanosclerosis. Laryngoscope 1977; 87: 1821-5. 11. Schiff M, Poliquin JF, Catanzaro A, Ryan AF. Tympanosclerosis. A theory of pathogenesis. Ann Otol Rhinol Laryngol Suppl 1980; 89: 1-16. 12. Forseni M, Bagger-Sjöback D, Hultcrantz M. A study of inflammatory mediators in the human tympanosclerotic middle ear. Arch Otolaryngol Head Neck Surg 2001; 127: 559-64. 13. Leal MC, Neto SSC, Caldas N, Peixoto CA, Lessa FJD, Leao BT, et al. Influence of hypercalsemia in the formation of tympanosclerosis in rat. Otol Neurotol 2005; 27: 27-32. 14. Tos M. Stangerup SE. Hearing loss in tympanosclerosis caused by grommets. Arch Otolaryngol Head Neck Surg 1989; 115: 931-5 15. Sheehy JL, House WF. Tympanosclerosis. Arch Otolaryngol 1962; 76: 151-7. 16. Tos M, Bak-Pedersen K. Middle-ear mucosa in tympanosclerosis. J Laryngol Otol 1974; 88: 119-26. 17. Costa SS, Paparella MM, Schachern PA, Yoon TH, Kimberley BP. Temporal bone histopathology in chronically infected ears with intact and perforated tympanic membranes. Laryngoscope 1992; 102: 1229-36. 18. Makiishi-Shimobayashi C, Tsujimura T, Sugihara A, Iwasaki T, Yamada N, Terada N, Sakagami M. Expression of osteopontin by exudate macrophages in infammatory tissues of the middle ear: a possible association with development of tympanosclerosis. Hear Res. 2001; 153: 100-7. 19. Bhaya MH, Schachern PA, Morizono T, Paparella MM. Pathogenesis of tympanosclerosis. Otolaryngol Head Neck Surg. 1993; 109: 413-20. 20. Polat S, Oztürk O, Uneri C, Yüksel M, Haklar G, Bozkurt S, et all. Determination of Reactive Oxygen Species in Myringotomized Tympanic Membranes: Effect of Vitamin E Treatment. Laryngoscope. 2004; 114: 720-5. 21. Albu S, Babighian G, and Trabalzini F. Surgical Treatment of Tympanosclerosis. The American Journal of Otology 2000; 21: 631-5. 22. Çakatay U. Pro-oxidant actions of α-lipoic acid and dihydrolipoic acid. Med Hypotheses. 2006; 66: 110-7. 23. Thirunavukkarasu V, Anuradha CV. Influence of alpha-lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin-resistant rats. Diabetes Obes Metab. 2004; 6: 200-7. 24. Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats. Chem Biol Interact. 2001; 138: 189-98. 25. Khanna S, Atalay M, Laaksonen DE, Gul M, Roy S, Sen CK. Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise. J Appl Physiol. 1999; 86: 1191-6. 26. Cummings BP, Stanhope KL, Graham JL, Evans JL, Baskin DG, Griffen SC, et al. Dietary fructose accelerates the development of diabetes in UCD-T2DM rats: amelioration by the antioxidant, alpha-lipoic acid. Am J Physiol Regul Integr Comp Physiol 2010; 298: 1343-50.