Advertisement

Protective Effects of Silymarin Against Age-Related Hearing Loss in an Aging Rat Model

  • Elham Tavanai
  • Ghassem Mohammadkhani
  • Saeid Farahani
  • Shohreh Jalaie
Original Article
  • 26 Downloads

Abstract

Age-related hearing loss (ARHL) is one of the most common chronic degenerative disorders. Several studies have indicated that supplementation with some antioxidants can slow down the progression of ARHL. Despite several lines of evidence about the potent antioxidant and anti-aging effects of silymarin, its protective effect against ARHL has not evaluated yet. The aim of the current study was to investigate the effects of silymarin in prevention of ARHL in a d-Galactose-induced aging rat model for the first time. 45 male wistar rats aged 3-month old were divided into 5 groups: group 1, 2 and 3 received 500 mg/kg/day d-Gal plus 100, 200 and 300 mg/kg/day silymarin respectively for 8 weeks, placebo group received 500 mg/kg/day d-Gal plus propylene glycol as placebo, and control group received normal saline during this period of time. Auditory brainstem responses were measured at several frequencies (4, 6, 8, 12 and 16 kHz) before and after the intervention. Placebo group and group 3 showed significant ABR threshold increase across frequencies of 4, 6, 16 kHz compared with the other groups (P < 0.05). However, rats treated with silymarin 100 and 200 mg/kg/day plus d-Gal did not show any significant ABR threshold shifts. Similarly, ABR amplitude of P2 at 4, 8 kHz and P1, P4 at 4 kHz in the placebo group and group 3 were decreased significantly compared with other groups (P < 0.05). However, no significant differences are found in ABR absolute and inter-peak latencies between groups (P > 0.05). The findings indicates that silymarin with doses of 100 and 200 mg/kg/day has protective effect against ARHL and it can be supplemented into the diet of older people to slow down the progression of age-related hearing loss.

Keywords

Silymarin Age-related hearing loss d-Galactose 

Notes

Acknowledgements

This research has been supported by Tehran University of Medical Sciences. The authors would also like to thank Goldaru for supplying pure silymarin powder.

Funding

The article was supported by Tehran University of Medical Sciences.

Compliance with Ethical Standards

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

  1. 1.
    Du Z, Yang Q, Liu L, Li S, Zhao J, Hu J, Liu C, Qian D, Gao C (2015) NADPH oxidase 2-dependent oxidative stress, mitochondrial damage and apoptosis in the ventral cochlear nucleus of d-galactose-induced aging rats. Neuroscience 286:281–292PubMedCrossRefGoogle Scholar
  2. 2.
    Seidman MD, Ahmad N, Bai U (2002) Molecular mechanisms of age-related hearing loss. Ageing Res Rev 1(3):331–343PubMedCrossRefGoogle Scholar
  3. 3.
    Seidman MD, Ahmad N, Joshi D, Seidman J, Thawani S, Quirk WS (2004) Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage. Acta Otolaryngol Suppl 552:16–24CrossRefGoogle Scholar
  4. 4.
    Mazelová J, Popelar J, Syka J (2003) Auditory function in presbycusis: peripheral vs. central changes. Exp Gerontol 38(1–2):87–94PubMedCrossRefGoogle Scholar
  5. 5.
    Gates GA, Mills JH (2005) Lancet. Presbycusis 366(9491):1111–1120Google Scholar
  6. 6.
    Chen B, Zhong Y, Peng W, Sun Y, Kong WJ (2010) Age-related changes in the central auditory system: comparison of d-galactose-induced aging rats and naturally aging rats. Brain Res 1344:43–53PubMedCrossRefGoogle Scholar
  7. 7.
    Han C, Someya S (2013) Mouse models of age-related mitochondrial neurosensory hearing loss. Mol Cell Neurosci 55:95–100PubMedCrossRefGoogle Scholar
  8. 8.
    Fetoni AR, Picciotti PM, Paludetti G, Troiani D (2011) Pathogenesis of presbycusis in animal models: a review. Exp Gerontol 46(6):413–425PubMedCrossRefGoogle Scholar
  9. 9.
    Perez P, Bao J (2011) Why do hair cells and spiral ganglion neurons in the cochlea die during aging? Aging Dis 2(3):231–241PubMedPubMedCentralGoogle Scholar
  10. 10.
    Someya S, Prolla TA (2010) Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mech Ageing Dev 131(7–8):480–486PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Yamasoba T, Someya S, Yamada C, Weindruch R, Prolla TA, Tanokura M (2007) Role of mitochondrial dysfunction and mitochondrial DNA mutations in age-related hearing loss. Hear Res 226(1–2):185–193PubMedCrossRefGoogle Scholar
  12. 12.
    Ateş NA, Unal M, Tamer L, Derici E, Karakaş S, Ercan B, Pata YS, Akbaş Y, Vayisoğlu Y, Camdeviren H (2005) Glutathione S-transferase gene polymorphisms in presbycusis. Otol Neurotol 26(3):392–397PubMedCrossRefGoogle Scholar
  13. 13.
    Bielefeld EC, Tanaka C, Chen GD, Henderson D (2010) Age-related hearing loss: is it a preventable condition? Hear Res 264(1–2):98–107PubMedCrossRefGoogle Scholar
  14. 14.
    Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T, Kondo K (2013) Current concepts in age-related hearing loss: epidemiology and mechanistic pathways. Hear Res 303:30–38PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Someya S, Tanokura M, Weindruch R, Prolla TA, Yamasoba T (2010) Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys. Curr Aging Sci 3(1):20–25PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Yin S, Yu Z, Sockalingam R, Bance M, Sun G, Wang J (2007) The role of mitochondrial DNA large deletion for the development of presbycusis in fischer 344 rats. Neurobiol Dis 27(3):370–377PubMedCrossRefGoogle Scholar
  17. 17.
    Du Z, Yang Y, Hu Y, Sun Y, Zhang S, Peng W, Zhong Y, Huang X, Kong W (2012) A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of d-galactose-induced aging rats. Hear Res 287(1–2):15–24PubMedCrossRefGoogle Scholar
  18. 18.
    Zhong Y, Hu YJ, Yang Y, Peng W, Sun Y, Chen B, Huang X, Kong WJ (2011) Contribution of common deletion to total deletion burden in mitochondrial DNA from inner ear of d-galactose-induced aging rats. Mutat Res 712(1–2):11–19PubMedCrossRefGoogle Scholar
  19. 19.
    Kong WJ, Hu YJ, Wang Q, Wang Y, Han YC, Cheng HM, Kong W, Guan MX (2006) The effect of the mtdna4834 deletion on hearing. Biochem Biophys Res Commun 344(1):425–430PubMedCrossRefGoogle Scholar
  20. 20.
    Bai U, Seidman MD, Hinojosa R, Quirk WS (1997) Mitochondrial DNA deletions associated with aging and possibly presbycusis: a human archival temporal bone study. Am J Otol 18:449–453PubMedGoogle Scholar
  21. 21.
    Böttger EC, Schacht J (2013) The mitochondrion: a perpetrator of acquired hearing loss. Hear Res 303:12–19PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Chen B, Zhong Y, Peng W, Sun Y, Hu YJ, Yang Y, Kong WJ (2011) Increased mitochondrial DNA damage and decreased base excision repair in the auditory cortex of d-galactose-induced aging rats. Mol Biol Rep 38(6):3635–3642PubMedCrossRefGoogle Scholar
  23. 23.
    Chen H, Tang J (2014) The role of mitochondria in age-related hearing loss. Biogerontology 15:13–19PubMedCrossRefGoogle Scholar
  24. 24.
    Le Prell CG, Yamashita D, Minami SB, Yamasoba T, Miller JM (2007) Mechanisms of noise-induced hearing loss indicate multiple methods of prevention. Hear Res 226(1–2):22–43PubMedCrossRefGoogle Scholar
  25. 25.
    Mohammadkhani G, Pourbakht A, Khanavi M, Faghihzadeh S (2013) Protective effect of silymarin on noise-induced hearing loss in guinea pigs. Iran Red Crescent Med J 15(11):e8890PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Ohinata Y, Miller JM, Altschuler RA, Schacht J (2000) Intense noise induces formation of vasoactive lipid peroxidation products in the cochlea. Brain Res 878:163–173PubMedCrossRefGoogle Scholar
  27. 27.
    Ohlemiller KK, Wright JS, Dugan LL (1999) Early elevation of cochlear reactive oxygen species following noise exposure. Audiol Neurootol 4:229–236PubMedCrossRefGoogle Scholar
  28. 28.
    Henderson D, Bielefeld EC, Harris KC, Hu BH (2006) The role of oxidative stress in noise-induced hearing loss. Ear Hear 27(1):1–19PubMedCrossRefGoogle Scholar
  29. 29.
    Fetoni AR, De Bartolo P, Eramo SLM, Rolesi R, Paciello F, Bergamini CH, Fato R, Paludetti G, Petrosini L, Troiani D (2013) Noise-induced hearing loss (NIHL) as a target of oxidative stress-mediated damage: cochlear and cortical responses after an increase in antioxidant defense. J Neurosci 33(9):4011–4023PubMedCrossRefGoogle Scholar
  30. 30.
    Kovacic P, Somanathan R (2008) Ototoxicity and noise trauma: electron transfer, reactive oxygen species, cell signaling, electrical effects, and protection by antioxidants: practical medical aspects. Med Hypotheses 70(5):914–923PubMedCrossRefGoogle Scholar
  31. 31.
    Poirrier AL, Pincemail J, Van Den Ackerveken P, Lefebvre PP, Malgrange B (2010) Oxidative stress in the cochlea: an update. Curr Med Chem 17(30):3591–3604PubMedCrossRefGoogle Scholar
  32. 32.
    Van de Water TR, Lallemend F, Eshraghi AA, Ahsan S, He J, Guzman J, Polak M, Malgrange B, Lefebvre PP, Staecker H, Balkany TJ (2004) Caspases, the enemy within, and their role in oxidative stress-induced apoptosis of inner ear sensory cells. Otol Neurotol 25(4):627–632CrossRefGoogle Scholar
  33. 33.
    Kopke R, Allen KA, Henderson D, Hoffer M, Frenz D, Van de Water T (1999) Toxins and trauma share common pathways in hair cell death. Ann N Y Acad Sci 28(884):171–191CrossRefGoogle Scholar
  34. 34.
    Neri S, Signorelli S, Pulvirenti D, Mauceri B, Cilio D, Bordonaro F, Abate G, Interlandi D, Misseri M, Ignaccolo L, Savastano M, Azzolina R, Grillo C, Messina A, Serra A, Tsami A (2006) Oxidative stress, nitric oxide, endothelial dysfunction and tinnitus. Free Radic Res 40(6):615–618PubMedCrossRefGoogle Scholar
  35. 35.
    Neri S, Mauceri B, Cilio D, Bordonaro F, Messina A, Malaguarnera M, Savastano M, Brescia G, Manci S, Celadini M (2002) Tinnitus and oxidative stress in a selected series of elderly patients. Arch Gerontol Geriatr 35:219–223CrossRefGoogle Scholar
  36. 36.
    Jiang H, Talaska AE, Schacht J, Sha SH (2007) Oxidative imbalance in the aging inner ear. Neurobiol Aging 28(10):1605–1612PubMedCrossRefGoogle Scholar
  37. 37.
    Le T, Keithley EM (2007) Effects of antioxidants on the aging inner ear. Hear Res 226(1–2):194–202PubMedCrossRefGoogle Scholar
  38. 38.
    Coling D, Chen S, Chi LH, Jamesdaniel S, Henderson D (2009) Age-related changes in antioxidant enzymes related to hydrogen peroxide metabolism in rat inner ear. Neurosci Lett 464(1):22–25PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Fujimoto C, Yamasoba T (2014) Oxidative stresses and mitochondrial dysfunction in age-related hearing loss. Oxid Med Cell Longev 2014:582849PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Benkafadar N (2015) Oxidative stress: key mechanism of age-related cochlear sensory hair cell loss. J Int Soc Antioxid Nutr Health. Special issue for 15th international antioxidants congress, vol 1, no 1Google Scholar
  41. 41.
    Coling DE, Yu KC, Somand D, Satar B, Bai U, Huang TT, Seidman MD, Epstein CJ, Mhatre AN, Lalwani AK (2003) Effect of SOD1 overexpression on age- and noise-related hearing loss. Free Radic Biol Med 34(7):873–880PubMedCrossRefGoogle Scholar
  42. 42.
    Kidd AR III, Bao J (2012) Recent advances in the study of age-related hearing loss—a mini-review. Gerontology 58(6):490–496PubMedCentralCrossRefGoogle Scholar
  43. 43.
    Darrat I, Ahmad N, Seidman K, Seidman MD (2007) Auditory research involving antioxidants. Curr Opin Otolaryngol Head Neck Surg 15(5):358–363PubMedCrossRefGoogle Scholar
  44. 44.
    Seidman MD (2000) Effects of dietary restriction and antioxidants on presbyacusis. Laryngoscope 110(5 Pt 1):727–738PubMedCrossRefGoogle Scholar
  45. 45.
    Someya S, Xu J, Kondo K, Ding D, Salvi RJ, Yamasoba T, Rabinovitch PS, Weindruch R, Leeuwenburgh C, Tanokura M, Prolla TA (2009) Age-related hearing loss in C57BL/6J mice is mediated by bak-dependent mitochondrial apoptosis. Proc Natl Acad Sci USA 106(46):19432–19437PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Peng W, Hu Y, Zhong Y, Chen B, Sun Y, Yang Y, Kong W (2010) Protective roles of alpha-lipoic acid in rat model of mitochondrial DNA4834 bp deletion in inner ear. J Huazhong Univ Sci Technolog Med Sci 30(4):514–518PubMedCrossRefGoogle Scholar
  47. 47.
    Romeo G, Giorgetti M (1985) Therapeutic effects of vitamin A associated with vitamin E in perceptual hearing loss. Acta Vitaminol Enzymol 7(1–2):139–143PubMedGoogle Scholar
  48. 48.
    Heman-Ackah SE, Juhn SK, Huang TC, Wiedmann TS (2010) A combination antioxidant therapy prevents age-related hearing loss in C57BL/6 mice. Otolaryngol Head Neck Surg 143(3):429–434PubMedCrossRefGoogle Scholar
  49. 49.
    Ding D, Jiang H, Chen GD, Longo-Guess C, Muthaiah VPK, Tian C, Sheppard A, Salvi R, Johnson KR (2016) N-acetyl-cysteine prevents age-related hearing loss and the progressive loss of inner hair cells in γ-glutamyl transferase 1 deficient mice. AGING 8(4):730PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Sanz-Fernández R, Sánchez-Rodriguez C, Granizo JJ, Durio-Calero E, Martín-Sanz E (2016) Accuracy of auditory steady state and auditory brainstem responses to detect the preventive effect of polyphenols on age-related hearing loss in Sprague–Dawley rats. Eur Arch Otorhinolaryngol 273(2):341–347PubMedCrossRefGoogle Scholar
  51. 51.
    Kang JW, Choi HS, Kim K, Choi JY (2014) Dietary vitamin intake correlates with hearing thresholds in the older population: the Korean National Health and Nutrition Examination Survey. Am J Clin Nutr 99(6):1407–1413PubMedCrossRefGoogle Scholar
  52. 52.
    Takumida M, Anniko M (2009) Radical scavengers for elderly patients with age-related hearing loss. Acta Otolaryngol 129(1):36–44PubMedCrossRefGoogle Scholar
  53. 53.
    Takumida M, Anniko M (2005) Radical scavengers: a remedy for presbyacusis. A pilot study. Acta Otolaryngol 125(12):1290–1295PubMedCrossRefGoogle Scholar
  54. 54.
    Seidman MD, Khan MJ, Tang WX, Quirk WS (2002) Influence of lecithin on mitochondrial DNA and age-related hearing loss. Otolaryngol Head Neck Surg 127(3):138–144PubMedCrossRefGoogle Scholar
  55. 55.
    Nevado J, Sanz R, Sánchez-Rodríguez C, García-Berrocal JR, Martín-Sanz E, González-García JA, Esteban-Sánchez J, Ramírez-Camacho R (2010) Ginkgo biloba extract (egb761) protects against aging-related caspase-mediated apoptosis in rat cochlea. Acta Otolaryngol 130(10):1101–1112PubMedCrossRefGoogle Scholar
  56. 56.
    Derin A, Agirdir B, Derin N, Dinç O, Güney K, Ozcaglar H, Kilinçarslan S (2004) The effects of l-carnitine on presbyacusis in the rat model. Clin Otolaryngol Allied Sci 29(3):238–241PubMedCrossRefGoogle Scholar
  57. 57.
    Salami A, Mora R, Dellepiane M, Manini G, Santomauro V, Barettini L, Guastini L (2010) Water-soluble coenzyme Q10 formulation (Q-TER(®)) in the treatment of presbycusis. Acta Otolaryngol 130(10):1154–1162PubMedCrossRefGoogle Scholar
  58. 58.
    Durga J, Verhoef P, Anteunis LJ, Schouten E, Kok FJ (2007) Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial. Ann Intern Med 146(1):1–9PubMedCrossRefGoogle Scholar
  59. 59.
    Ahn JH, Kang HH, Kim TY, Shin JE, Chung JW (2008) Lipoic acid rescues DBA mice from early-onset age-related hearing impairment. NeuroReport 19(13):1265–1269PubMedCrossRefGoogle Scholar
  60. 60.
    Bielefeld EC, Coling D, Chen GD, Henderson D (2008) Multiple dosing strategies with acetyl l-carnitine (ALCAR) fail to alter age-related hearing loss in the Fischer 344/nhsd rat. J Negat Results Biomed 7:4PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Sha SH, Kanicki A, Halsey K, Wearne KA, Schacht J (2012) Antioxidant-enriched diet does not delay the progression of age-related hearing loss. Neurobiol Aging 33(5):1010.e15–1010.e16CrossRefGoogle Scholar
  62. 62.
    Kashio A, Amano A, Kondo Y, Sakamoto T, Iwamura H, Suzuki M, Ishigami A, Yamasoba T (2009) Effect of vitamin C depletion on age-related hearing loss in SMP30/GNL knockout mice. Biochem Biophys Res Commun 390(3):394–398PubMedCrossRefGoogle Scholar
  63. 63.
    Shargorodsky J, Curhan SG, Eavey R, Curhan GC (2010) A prospective study of vitamin intake and the risk of hearing loss in men. Otolaryngol Head Neck Surg 142(2):231–236PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Polanski JF, Cruz OL (2013) Evaluation of antioxidant treatment in presbycusis: prospective, placebo-controlled, double-blind, randomised trial. J Laryngol Otol 127(2):134–141PubMedCrossRefGoogle Scholar
  65. 65.
    Davis RR, Kuo MW, Stanton SG, Canlon B, Krieg E, Alagramam KN (2007) N-Acetyl l-cysteine does not protect against premature age-related hearing loss in C57BL/6 J mice: a pilot study. Hear Res 226(1–2):203–208PubMedCrossRefGoogle Scholar
  66. 66.
    Katiyar S (2005) Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (review). Int J Oncol 26:169–176PubMedGoogle Scholar
  67. 67.
    Křena V, Walterováb D (2005) Silybin and silymarin—new effects and applications. Biomed Pap 149(1):29–41CrossRefGoogle Scholar
  68. 68.
    Bakhshaee M, Jabbari F, Hoseini S, Farid R, Sadeghian MH, Rajati M et al (2011) Effect of silymarin in the treatment of allergic rhinitis. Otolaryngol Head Neck Surg 145(6):904–909PubMedCrossRefGoogle Scholar
  69. 69.
    Oliveirra C, Lapasoo F, Laurindo F, Leitão RMC, Laudanna AA (2001) Protection against liver ischemia—reperfusion injury in rats by silymarin or verapamil. Transplant Proc 33(6):3010–3014CrossRefGoogle Scholar
  70. 70.
    Rasul A, Akhtar N, Ali Khan B, Mahmood T, Uz Zaman SH, Ali A et al (2011) Assessment of anti erythmic and skin whitening effects of milk thistle extract. Afr J Pharm Pharmacol 5(20):2306–2309Google Scholar
  71. 71.
    Katiyar SK, Mantena SK, Meeran SM (2011) Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced apoptosis and DNA damage by nucleotide excision repair mechanism. PloS ONE 6(6):e21410PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Gazák R, Walterová D, Kren V (2007) Silybin and silymarin-new and emerging applications in medicine. Curr Med Chem 14(3):315–338PubMedCrossRefGoogle Scholar
  73. 73.
    Cho SI, Lee JE, Yong DN (2014) Protective effect of silymarin against cisplatin-induced ototoxicity. Int J Pediatr Otorhinolaryngol 78:474–478PubMedCrossRefGoogle Scholar
  74. 74.
    Draz E, Abdin A, Sarhan N, Gabr T (2015) Neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity in guinea pigs. Pharmacol Rep 67(2):317–325PubMedCrossRefGoogle Scholar
  75. 75.
    Najafzadeh H, Esmailzadeh S, Morovvati H, Avizeh R, Ezati M (2010) Protective effect of silymarin and vitamin E on gentamicin-induced pathological changes in kidney of dog. Iran J Med Aromat Plants 26(1):91–100Google Scholar
  76. 76.
    Mohammadirad A, Aghamohammadali-Sarraf F, Badiei S, Faraji Z, Hajiaghaee R, Baeeri M et al (2013) Anti-aging effects of some selected Iranian folk medicinal herbs-biochemical evidences. Iran J Basic Med Sci 16(11):1170PubMedPubMedCentralGoogle Scholar
  77. 77.
    Zhu SY, Dong Y, Tu J, Zhou Y, Zhou XH, Bin Xu (2014) Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with d-galactose. Pharmacogn Mag 10(1):92–99Google Scholar
  78. 78.
    Hadzi-Petrushev N, Stojkovski V, Mitrov D, Mladenov M (2015) d-galactose induced changes in enzymatic antioxidant status in rats of different ages. Physiol Res 64:61–70PubMedGoogle Scholar
  79. 79.
    Wu L, Sun Y, Hu YJ et al (2012) Increased p66Shc in the inner ear of d-galactose-induced aging mice with accumulation of mitochondrial DNA 3873-bp deletion: p66Shc and mtDNA damage in the inner ear during aging. PloS ONE 7:e50483PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Zhong Y, Hu YJ, Chen B et al (2011) Mitochondrial transcription factor a overexpression and base excision repair deficiency in the inner ear of rats with d-galactose-induced aging. FEBS J 278:2500–2510PubMedCrossRefGoogle Scholar
  81. 81.
    Zhong Y, Hu Y, Peng W et al (2012) Age-related decline of the cytochrome coxidase subunit expression in the auditory cortex of the mimetic aging rat model associated with the common deletion. Hear Res 294:40–48PubMedCrossRefGoogle Scholar
  82. 82.
    Du Z, Li SH, Liu L, Yang Q, Zhang H, Gao CH (2015) NADPH oxidase 3-associated oxidative stress and caspase 3-dependent apoptosis in the cochleae of d-galactose-induced aged rats. Mol Med Rep 12(6):7883–7890PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Du Z, Yang Q, Zhou T, Liu L, Li SH, Chen SH, Gao CH (2014) d-galactose-induced mitochondrial DNA oxidative damage in the auditory cortex of rats. Mol Med Rep 10(6):2861–2867PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Kong W, Hu Y, Wang Q, Xu L, Wang Y, Han Y, Li J, Liu B, Kong W (2006) Establishment of model with inner ear mimetic aging and mtDNA 4834 bp deletion in rats. J Clin Otolaryngol 20(19):888–890Google Scholar
  85. 85.
    Kong W, Wang Y, Wang Q, Hu YJ, Han Y, Liu J (2006) The relation between d-galactose injection and mitochondrial DNA4834 bp deletion mutation. Exp Gerontol 41:628–634PubMedCrossRefGoogle Scholar
  86. 86.
    Tavanai E, Mohammadkhani GH (2017) Role of antioxidants in prevention of ade-related hearing loss: a review of literature. Eur Arch Otolaryngol 274(4):1821–1834CrossRefGoogle Scholar
  87. 87.
    Kapoor VK, Dureja J, Chadha R (2009) Herbals in the control of ageing. Drug Discov Today 14(19):992–998PubMedCrossRefGoogle Scholar
  88. 88.
    Ghosh A, Ghosh T, Jain S (2010) Silymarin-a review on the pharmacodynamics and bioavailability enhancement approaches. J Pharm Sci Technol 2(10):348–355Google Scholar
  89. 89.
    Dixit N, Baboota S, Kohli K, Ahmad S, Ali J (2007) Silymarin: a review of pharmacological aspects and bioavailability enhancement approaches. Indian J Pharmacol 39(4):172–179CrossRefGoogle Scholar
  90. 90.
    Zarban A, Masood Z (2008) Evaluation of antioxidant properties of silymarin and its potential to inhibit peroxyl radicals in vitro. Pak J Pharm Sci 21(3):249–254Google Scholar
  91. 91.
    Surai PF (2015) Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants 4(1):204–247PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Hosny Mansour H, Farouk Hafez H, Mohamed FN (2006) Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol 39(6):656–661Google Scholar
  93. 93.
    Mayer KE, Myers RP, Lee SS (2005) Silymarin treatment of viral hepatitis: a systematic review. J Viral Hepat 12(6):559–567PubMedCrossRefGoogle Scholar
  94. 94.
    Karimi GH, Ramezani M, Tahoonian Z (2005) Cisplatin nephrotoxicity and protection by milk thistle extract in rats. ECAM 2(3):383–386PubMedPubMedCentralGoogle Scholar
  95. 95.
    Leitron PH, Labbe G, Degorr C, Berson TA, Fromenty B, Delaforge M et al (1990) Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Biochem Pham 39(12):2027–2034CrossRefGoogle Scholar
  96. 96.
    Miguez MP, Anundi I, Sainz-Pardo LA, Lindros KO (1994) A hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2el. Chem Biol Interact 91:51–63PubMedCrossRefGoogle Scholar
  97. 97.
    Saller R, Melzer J, Reichling J, Brignoli R, Meier R (2007) An updated systematic review of the pharmacology of silymarin. Forsch Komplementärmed 14:70–80Google Scholar
  98. 98.
    Sasu A, Herman H, Folk A, Baltǎ C, Roşu M, Miuţescu E et al (2016) Protective effects of silymarin on epirubicin-induced hepatotoxicity in mice. Studia Universitatis Vasile Goldiş Seria Ştiinţele Vieţi 26(3):305–316Google Scholar
  99. 99.
    Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB (1999) Silymarin suppresses TNF-induced activation of NF-κb, c-Jun N-terminal kinase, and apoptosis. J Immunol 163(12):6800–6809PubMedGoogle Scholar
  100. 100.
    Ruan Q, Ma C, Zhang R, Yu Z (2014) Current status of auditory aging and anti-aging research. Geriatr Gerontol Int 14(1):40–53PubMedCrossRefGoogle Scholar
  101. 101.
    Tadros SF, D’Souza M, Zhu X, Frisina RD (2008) Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea. Apoptosis 13(11):1303PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Varga Z, Ujhelyi L, Kiss A, Balla J, Czompa A, Antus S (2004) Effect of silybin on phorbol myristate actetate-induced protein kinase C translocation, NADPH oxidase activity and apoptosis in human neutrophils. Phytomedicine 11(2–3):206–212PubMedCrossRefGoogle Scholar
  103. 103.
    Menardo J, Tang Y, Ladrech S, Lenoir M, Fo C, Michel C et al (2012) Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8 mouse Cochlea. Antioxid Redox Signal 16(3):263–274PubMedCrossRefGoogle Scholar
  104. 104.
    Verschuur C, Agyemang-Prempeh A, Newman TA (2014) Inflammation is associated with a worsening of presbycusis: evidence from the MRC national study of hearing. Int J Audiol 53(7):469–475PubMedCrossRefGoogle Scholar
  105. 105.
    Kim H-J, Oh G-S, Choe S-K, Kwak TH, Park R, So H-S (2014) NAD+ metabolism in age-related hearing loss. Aging Dis 5(2):150PubMedPubMedCentralGoogle Scholar
  106. 106.
    Soto C, Mena R, Luna J, Cerbon M, Larrieta E, Vital P et al (2004) Silymarin induces recovery of pancreatic function after alloxan damage in rats. Life Sci 75(18):2167–2180PubMedCrossRefGoogle Scholar
  107. 107.
    Nencini C, Giorgi G, Micheli L (2007) Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine 14(2):129–135PubMedCrossRefGoogle Scholar
  108. 108.
    El Mesallamy HO, Metwally NS, Soliman MS, Ahmed KA, Moaty MMA (2011) The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats. Cancer Cell Int 11(1):38PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Association of Otolaryngologists of India 2018

Authors and Affiliations

  • Elham Tavanai
    • 1
  • Ghassem Mohammadkhani
    • 1
  • Saeid Farahani
    • 1
  • Shohreh Jalaie
    • 1
  1. 1.Department of Audiology, School of RehabilitationTehran University of Medical SciencesTehranIran

Personalised recommendations