Pharmaceutical characterization of probucol bile acid–lithocholic acid nanoparticles to prevent chronic hearing related and similar cellular oxidative stress pathologies

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Henderson D, Bielefeld EC, Harris KC, Hu BH. The role of oxidative stress in noise-induced hearing loss. Ear Hear. 27(1), 1–19 (2006).
  MedlineGoogle Scholar
• 2. Menardo J, Tang Y, Ladrech S et al. 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), 263–274 (2012).
  Medline CASGoogle Scholar
• 3. Elias TGA, Monsanto RDC, do Amaral JB, Oyama LM, Maza PK, Penido NO. Evaluation of oxidative-stress pathway and recovery of sudden sensorineural hearing loss. Int. Arch. Otorhinolaryngol. 25(3), e428–e432 (2021).
  MedlineGoogle Scholar
• 4. Böttger EC, Schacht J. The mitochondrion: a perpetrator of acquired hearing loss. Hear. Res. 303, 12–19 (2013).
  Medline CASGoogle Scholar
• 5. Nakae S, Tachibana M. The cochlea of the spontaneously diabetic mouse. Arch. Otorhinolaryngol. 243(5), 313–316 (1986).
  Medline CASGoogle Scholar
• 6. Raynor EM, Carrasco VN, Prazma J, Pillsbury HC. An assessment of cochlear hair-cell loss in insulin-dependent diabetes mellitus diabetic and noise-exposed rats. Arch. Otolaryngol. Head Neck Surg. 121(4), 452–456 (1995).
  Medline CASGoogle Scholar
• 7. Chester J, Johnston E, Walker D et al. A review on recent advancement on age-related hearing loss: the applications of nanotechnology, drug pharmacology, and biotechnology. Pharmaceutics 13(7), 1041 (2021). • Review which explains the importance of bile acid-based nanotechnology in drug-delivery systems.
  Medline CASGoogle Scholar
• 8. Zimetbaum P, Eder H, Frishman W. Probucol: pharmacology and clinical application. J. Clin. Pharmacol. 30(1), 3–9 (1990).
  Medline CASGoogle Scholar
• 9. Yamashita S, Matsuzawa Y. Where are we with probucol: a new life for an old drug? Atherosclerosis 207(1), 16–23 (2009).
  Medline CASGoogle Scholar
• 10. Bueno DC, Canto RFS, de Souza V et al. New probucol analogues inhibit ferroptosis, improve mitochondrial parameters, and induce glutathione peroxidase in HT22 cells. Mol. Neurobiol. 57(8), 3273–3290 (2020).
  Medline CASGoogle Scholar
• 11. Heel R, Brogden R, Speight T, Avery G. Probucol: a review of its pharmacological properties and therapeutic use in patients with hypercholesterolaemia. Drugs 15(6), 409–428 (1978).
  Medline CASGoogle Scholar
• 12. Mamo JC, Lam V, Brook E et al. Probucol prevents blood–brain barrier dysfunction and cognitive decline in mice maintained on pro-diabetic diet. Diab. Vasc. Dis. Res. 16(1), 87–97 (2019).
  Medline CASGoogle Scholar
• 13. Wagle SR, Kovacevic B, Walker D et al. Alginate-based drug oral targeting using bio-micro/nano encapsulation technologies. Expert Opin. Drug Deliv. 17(10), 1361–1376 (2020). • Review which explains that bile acid and nanotechnology could be one promising strategy to improve the therapeutic effectiveness of lipophilic drugs.
  Medline CASGoogle Scholar
• 14. Li F, Li L, Wang S et al. Improved dissolution and oral absorption by co-grinding active drug probucol and ternary stabilizers mixtures with planetary beads-milling method. Asian J. Pharm. Sci. 14(6), 649–657 (2019).
  MedlineGoogle Scholar
• 15. Yehye WA, Rahman NA, Ariffin A et al. Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review. Eur. J. Med. Chem. 101, 295–312 (2015).
  Medline CASGoogle Scholar
• 16. Mathavan S, Chen-Tan N, Arfuso F, Al-Salami H. A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of type-1 diabetes. Drug Deliv. 23(8), 2869–2880 (2016).
  Medline CASGoogle Scholar
• 17. Mikov M, Al-Salami H, Golocorbin-Kon S, Skrbic R, Raskovic A, Fawcett JP. The influence of 3α,7α-dihydroxy-12-keto-5β-cholanate on gliclazide pharmacokinetics and glucose levels in a rat model of diabetes. Eur. J. Drug Metab. Pharmacokinet. 33(3), 137–142 (2008).
  Medline CASGoogle Scholar
• 18. Mooranian A, Negrulj R, Mathavan S et al. An advanced microencapsulated system: a platform for optimized oral delivery of antidiabetic drug-bile acid formulations. Pharm. Dev. Technol. 20(6), 702–709 (2015).
  Medline CASGoogle Scholar
• 19. Stojančević M, Pavlović N, Goločorbin-Kon S, Mikov M. Application of bile acids in drug formulation and delivery. Front. Life Sci. 7(3–4), 112–122 (2013).
  CASGoogle Scholar
• 20. Kovacevic B, Jones M, Ionescu C et al. The emerging role of bile acids as critical components in nanotechnology and bioengineering: pharmacology, formulation optimizers and hydrogel–biomaterial applications. Biomaterials 283, 121459 (2022). • Explores bile acids’ role and mechanism as permeation enhancers in drug delivery.
  Medline CASGoogle Scholar
• 21. Mooranian A, Negrulj R, Takechi R, Mamo J, Al-Sallami H, Al-Salami H. The biological effects of the hypolipidaemic drug probucol microcapsules fed daily for 4 weeks, to an insulin-resistant mouse model: potential hypoglycaemic and anti-inflammatory effects. Drug Deliv. Transl. Res. 8(3), 543–551 (2018).
  Medline CASGoogle Scholar
• 22. Mooranian A, Negrulj R, Chen-Tan N et al. Advanced bile acid-based multi-compartmental microencapsulated pancreatic β-cells integrating a polyelectrolyte-bile acid formulation, for diabetes treatment. Artif. Cells Nanomed. Biotechnol. 44(2), 588–595 (2016).
  Medline CASGoogle Scholar
• 23. Mooranian A, Negrulj R, Mikov M, Golocorbin-Kon S, Arfuso F, Al-Salami H. Novel chenodeoxycholic acid–sodium alginate matrix in the microencapsulation of the potential antidiabetic drug, probucol. An in vitro study. J. Microencapsul. 32(6), 589–597 (2015).
  Medline CASGoogle Scholar
• 24. Mooranian A, Raj Wagle S, Kovacevic B et al. Bile acid bio-nanoencapsulation improved drug targeted-delivery and pharmacological effects via cellular flux: 6-months diabetes preclinical study. Sci. Rep. 10(1), 106 (2020). •• Here we showed that probucol–bile acid microcapsules positively affected β-cells’ viability in the hyperglycemic state, and brought about hypoglycemic and anti-inflammatory effects on prediabetic mice.
  Medline CASGoogle Scholar
• 25. Wagle SR, Walker D, Kovacevic B et al. Micro-nano formulation of bile–gut delivery: rheological, stability and cell survival, basal and maximum respiration studies. Sci. Rep. 10(1), 7715 (2020).
  Medline CASGoogle Scholar
• 26. Yao B, He J, Yin X, Shi Y, Wan J, Tian Z. The protective effect of lithocholic acid on the intestinal epithelial barrier is mediated by the vitamin D receptor via a SIRT1/Nrf2 and NF-κB dependent mechanism in Caco-2 cells. Toxicol. Lett. 316, 109–118 (2019).
  Medline CASGoogle Scholar
• 27. Wagle SR, Kovacevic B, Ionescu CM et al. Pharmacological and biological study of microencapsulated probucol-secondary bile acid in a diseased mouse model. Pharmaceutics 13(8), 1223 (2021). •• Here we showed that probucol–lithocholic acid-based microcapsules may be a promising therapy for treating diabetes mellitus.
  Medline CASGoogle Scholar
• 28. Pavlovic N, Golocorbin-Kon S, Ethanic M et al. Bile acids and their derivatives as potential modifiers of drug release and pharmacokinetic profiles. Front. Pharmacol. 9, 1283 (2018).
  MedlineGoogle Scholar
• 29. Sukmawati A, Utami W, Yuliani R, Da'i M, Nafarin A. Effect of Tween 80 on nanoparticle preparation of modified chitosan for targeted delivery of combination doxorubicin and curcumin analogue. IOP Conf. Ser. Mater. Sci. Eng. 311, 012024 (2018).
  Google Scholar
• 30. Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm. Res. 23(12), 2709–2728 (2006).
  Medline CASGoogle Scholar
• 31. Lee CH, Singla A, Lee Y. Biomedical applications of collagen. Int. J. Pharm. 221(1–2), 1–22 (2001).
  Medline CASGoogle Scholar
• 32. Goh CH, Heng PWS, Chan LW. Alginates as a useful natural polymer for microencapsulation and therapeutic applications. Carbohydr. Polym. 88(1), 1–12 (2012).
  CASGoogle Scholar
• 33. Tomeh MA, Hadianamrei R, Zhao X. Silk fibroin as a functional biomaterial for drug and gene delivery. Pharmaceutics 11(10), 494 (2019).
  Medline CASGoogle Scholar
• 34. Oliveira RN, Rouzé R, Quilty B et al. Mechanical properties and in vitro characterization of polyvinyl alcohol-nano-silver hydrogel wound dressings. Interface Focus 4(1), 20130049 (2014).
  Medline CASGoogle Scholar
• 35. Kumar R, Siril PF. Preparation and characterization of polyvinyl alcohol stabilized griseofulvin nanoparticles. Mater. Today Proc. 3(6), 2261–2267 (2016).
  Google Scholar
• 36. Chakraborty G, Bhattarai A, De R. Polyelectrolyte–dye interactions: an overview. Polymers 14(3), 598 (2022).
  Medline CASGoogle Scholar
• 37. Panacek A, Prucek R, Hrbac J et al. Polyacrylate-assisted size control of silver nanoparticles and their catalytic activity. Chem. Mater. 26(3), 1332–1339 (2014).
  CASGoogle Scholar
• 38. Almansour K, Ali R, Alheibshy F et al. Particle engineering by nano spray drying: optimization of process parameters with hydroethanolic versus aqueous solutions. Pharmaceutics 14(4), 800 (2022).
  Medline CASGoogle Scholar
• 39. Wagle SR, Kovacevic B, Walker D et al. Pharmacological and advanced cell respiration effects, enhanced by toxic human-bile nano-pharmaceuticals of probucol cell-targeting formulations. Pharmaceutics 12(8), 708 (2020).
  Medline CASGoogle Scholar
• 40. Mooranian A, Negrulj R, Al-Sallami HS et al. Probucol release from novel multicompartmental microcapsules for the oral targeted delivery in type 2 diabetes. AAPS PharmSciTech 16(1), 45–52 (2015).
  Medline CASGoogle Scholar
• 41. Salt AN, Hartsock JJ, Gill RM, Piu F, Plontke SK. Perilymph pharmacokinetics of markers and dexamethasone applied and sampled at the lateral semi-circular canal. J. Assoc. Res. Otolaryngol. 13(6), 771–783 (2012).
  MedlineGoogle Scholar
• 42. Yagi N, Terashima Y, Kenmotsu H, Sekikawa H, Takada M. Dissolution behavior of probucol from solid dispersion systems of probucol-polyvinylpyrrolidone. Chem. Pharm. Bull. 44(1), 241–244 (1996).
  CASGoogle Scholar
• 43. Uhljar LÉ, Kan SY, Radacsi N, Koutsos V, Szabó-Révész P, Ambrus R. In vitro drug release, permeability, and structural test of ciprofloxacin-loaded nanofibers. Pharmaceutics 13(4), 556 (2021).
  Medline CASGoogle Scholar
• 44. Kalinec G, Thein P, Park C, Kalinec F. HEI-OC1 cells as a model for investigating drug cytotoxicity. Hear. Res. 335, 105–117 (2016).
  Medline CASGoogle Scholar
• 45. Kalinec GM, Park C, Thein P, Kalinec F. Working with auditory HEI-OC1 cells. J. Vis. Exp. (115), 54425 (2016).
  MedlineGoogle Scholar
• 46. Wu M, Neilson A, Swift AL et al. Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells. Am. J. Physiol. Cell Physiol. 292(1), C125–C136 (2007).
  Medline CASGoogle Scholar
• 47. Wolfe KL, Liu RH. Cellular antioxidant activity (CAA) assay for assessing antioxidants, foods, and dietary supplements. J. Agric. Food Chem. 55(22), 8896–8907 (2007).
  Medline CASGoogle Scholar
• 48. Liao W, Ning Z, Chen L et al. Intracellular antioxidant detoxifying effects of diosmetin on 2, 2-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress through inhibition of reactive oxygen species generation. J. Agric. Food Chem. 62(34), 8648–8654 (2014).
  Medline CASGoogle Scholar
• 49. Kellett ME, Greenspan P, Pegg RB. Modification of the cellular antioxidant activity (CAA) assay to study phenolic antioxidants in a Caco-2 cell line. Food Chem. 244, 359–363 (2018).
  Medline CASGoogle Scholar
• 50. Xiao F, Xu T, Lu B, Liu R. Guidelines for antioxidant assays for food components. Food Front. 1(1), 60–69 (2020).
  Google Scholar
• 51. Yarnpakdee S, Benjakul S, Kristinsson HG, Bakken HE. Preventive effect of Nile tilapia hydrolysate against oxidative damage of HepG2 cells and DNA mediated by H₂O₂ and AAPH. J. Food Sci. Technol. 52(10), 6194–6205 (2015).
  Medline CASGoogle Scholar
• 52. Ajun W, Yan S, Li G, Huili L. Preparation of aspirin and probucol in combination loaded chitosan nanoparticles and in vitro release study. Carbohydr. Polym. 75(4), 566–574 (2009).
  Google Scholar
• 53. Lu P-J, Fu W-E, Huang S-C et al. Methodology for sample preparation and size measurement of commercial ZnO nanoparticles. J. Food Drug Anal. 26(2), 628–636 (2018).
  Medline CASGoogle Scholar
• 54. Malamatari M, Somavarapu S, Kachrimanis K, Buckton G, Taylor KMG. Preparation of respirable nanoparticle agglomerates of the low melting and ductile drug ibuprofen: impact of formulation parameters. Powder Technol. 308, 123–134 (2017).
  CASGoogle Scholar
• 55. Malamatari M, Charisi A, Malamataris S, Kachrimanis K, Nikolakakis I. Spray drying for the preparation of nanoparticle-based drug formulations as dry powders for inhalation. Processes 8(7), 788 (2020).
  CASGoogle Scholar
• 56. Danaei M, Dehghankhold M, Ataei S et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 10(2), 57 (2018).
  MedlineGoogle Scholar
• 57. Mooranian A, Negrulj R, Arfuso F, Al-Salami H. The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study. Drug Deliv. Transl. Res. 5(5), 511–522 (2015).
  Medline CASGoogle Scholar
• 58. Meier W. Polymer nanocapsules. Chem. Soc. Rev. 29(5), 295–303 (2000).
  CASGoogle Scholar
• 59. Mooranian A, Negrulj R, Chen-Tan N et al. Microencapsulation as a novel delivery method for the potential antidiabetic drug, probucol. Drug Des. Devel. Ther. 8, 1221 (2014).
  MedlineGoogle Scholar
• 60. Goycoolea MV. Clinical aspects of round window membrane permeability under normal and pathological conditions. Acta Otolaryngol. 121(4), 437–447 (2001).
  Medline CASGoogle Scholar
• 61. Draget KI, Taylor C. Chemical, physical and biological properties of alginates and their biomedical implications. Food Hydrocolloids 25(2), 251–256 (2011).
  CASGoogle Scholar
• 62. Pamies R, Schmidt RR, del Carmen López Martínez M, de la Torre JG. The influence of mono and divalent cations on dilute and non-dilute aqueous solutions of sodium alginates. Carbohydr. Polym. 80(1), 248–253 (2010).
  CASGoogle Scholar
• 63. Mooranian A, Negrulj R, Chen-Tan N, Watts GF, Arfuso F, Al-Salami H. An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid) as a permeation enhancer. Drug Des. Devel. Ther. 8, 1673 (2014).
  MedlineGoogle Scholar
• 64. Mooranian A, Negrulj R, Mathavan S et al. Stability and release kinetics of an advanced gliclazide-cholic acid formulation: the use of artificial-cell microencapsulation in slow release targeted oral delivery of antidiabetics. J. Pharm. Innov. 9, 150–157 (2014).
  MedlineGoogle Scholar
• 65. Loebel C, Rodell CB, Chen MH, Burdick JA. Shear-thinning and self-healing hydrogels as injectable therapeutics and for 3D-printing. Nat. Protoc. 12(8), 1521–1541 (2017).
  Medline CASGoogle Scholar
• 66. Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Trop. J. Pharm. Res. 12(2), 265–273 (2013).
  Google Scholar
• 67. Xie HG, Li XX, Lv GJ et al. Effect of surface wettability and charge on protein adsorption onto implantable alginate–chitosan–alginate microcapsule surfaces. J. Biomed. Mater. Res. A 92(4), 1357–1365 (2010).
  MedlineGoogle Scholar
• 68. Madenci D, Egelhaaf S. Self-assembly in aqueous bile salt solutions. Curr. Opin. Colloid Interface Sci. 15(1–2), 109–115 (2010).
  CASGoogle Scholar
• 69. Azarbayjani AF, Jouyban A, Chan SY. Impact of surface tension in pharmaceutical sciences. J. Pharm. Pharm. Sci. 12(2), 218–228 (2009).
  MedlineGoogle Scholar
• 70. Mooranian A, Carey L, Ionescu CM et al. The effects of accelerated temperature-controlled stability systems on the release profile of primary bile acid-based delivery microcapsules. Pharmaceutics 13(10), 1667 (2021).
  Medline CASGoogle Scholar
• 71. Negrulj R, Mooranian A, Chen-Tan N et al. Swelling, mechanical strength, and release properties of probucol microcapsules with and without a bile acid, and their potential oral delivery in diabetes. Artif. Cells Nanomed. Biotechnol. 44(5), 1290–1297 (2016).
  Medline CASGoogle Scholar
• 72. Zou J, Saulnier P, Perrier T et al. Distribution of lipid nanocapsules in different cochlear cell populations after round window membrane permeation. J. Biomed. Mater. Res. B Appl. Biomater. 87B(1), 10–18 (2008).
  CASGoogle Scholar
• 73. Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J. Control. Rel. 73(2), 121–136 (2001).
  Medline CASGoogle Scholar
• 74. Shively ML, Coonts BA, Renner WD, Southard JL, Bennett AT. Physico-chemical characterization of a polymeric injectable implant delivery system. J. Control. Rel. 33(2), 237–243 (1995).
  CASGoogle Scholar
• 75. Jeong B, Bae YH, Kim SW. Drug release from biodegradable injectable thermosensitive hydrogel of PEG–PLGA–PEG triblock copolymers. J. Control. Rel. 63(1–2), 155–163 (2000).
  Medline CASGoogle Scholar
• 76. Valentini C, Szeto B, Kysar JW, Lalwani AK. Inner ear gene delivery: vectors and routes. Hear. Balance Commun. 18(4), 278–285 (2020).
  Google Scholar
• 77. Fukui H, Raphael Y. Gene therapy for the inner ear. Hear. Res. 297, 99–105 (2013).
  Medline CASGoogle Scholar
• 78. Praetorius M, Brunner C, Lehnert B et al. Transsynaptic delivery of nanoparticles to the central auditory nervous system. Acta Otolaryngol. 127(5), 486–490 (2007).
  Medline CASGoogle Scholar
• 79. Pyykkö I, Zou J, Schrott-Fischer A, Glueckert R, Kinnunen P. An overview of nanoparticle based delivery for treatment of inner ear disorders. Methods Mol. Biol. 1427, 363–415 (2016).
  Medline CASGoogle Scholar
• 80. Szeto B, Chiang H, Valentini C, Yu M, Kysar JW, Lalwani AK. Inner ear delivery: challenges and opportunities. Laryngoscope Investig. Otolaryngol. 5(1), 122–131 (2019).
  MedlineGoogle Scholar
• 81. Peluso I, Campolongo P, Valeri P, Romanelli L, Palmery M. Intestinal motility disorder induced by free radicals: a new model mimicking oxidative stress in gut. Pharmacol. Res. 46(6), 533–538 (2002).
  Medline CASGoogle Scholar
• 82. Moreira Gomes MD, Carvalho G, Casquilho NV et al. 2,2′-azobis (2-amidinopropane) dihydrochloride is a useful tool to impair lung function in rats. Front. Physiol. 7, 475 (2016).
  MedlineGoogle Scholar
• 83. Zimowska W, Motyl T, Skierski J et al. Apoptosis and Bcl-2 protein changes in L1210 leukaemic cells exposed to oxidative stress. Apoptosis 2(6), 529–539 (1997).
  Medline CASGoogle Scholar
• 84. Cadenas E, Sies H. The lag phase. Free Radic. Res. 28(6), 601–609 (1998).
  Medline CASGoogle Scholar
• 85. Terao K, Niki E. Damage to biological tissues induced by radical initiator 2,2′-azobis (2-amidinopropane) dihydrochloride and its inhibition by chain-breaking antioxidants. J. Free Radic. Biol. Med. 2(3), 193–201 (1986).
  Medline CASGoogle Scholar
• 86. Ward JBJ, Lajczak NK, Kelly OB et al. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am. J. Physiol. Gastrointest. Liver Physiol. 312(6), G550–G558 (2017).
  MedlineGoogle Scholar
• 87. Brand MD, Nicholls DG. Assessing mitochondrial dysfunction in cells. Biochem. J. 435(2), 297–312 (2011).
  Medline CASGoogle Scholar
• 88. Joachims HZ, Segal J, Golz A, Netzer A, Goldenberg D. Antioxidants in treatment of idiopathic sudden hearing loss. Otol. Neurotol. 24(4), 572–575 (2003).
  MedlineGoogle Scholar
• 89. Laurell G, Teixeira M, Sterkers O et al. Local administration of antioxidants to the inner ear: kinetics and distribution. Hear. Res. 173(1), 198–209 (2002).
  Medline CASGoogle Scholar
• 90. Fujimoto C, Yamasoba T. Mitochondria-targeted antioxidants for treatment of hearing loss: a systematic review. Antioxidants 8(4), 109 (2019).
  Medline CASGoogle Scholar
• 91. Lyu A-R, Kim T-H, Shin S-A et al. Hearing impairment in a mouse model of diabetes is associated with mitochondrial dysfunction, synaptopathy, and activation of the intrinsic apoptosis pathway. Int. J. Mol. Sci. 22(16), 8807 (2021).
  Medline CASGoogle Scholar
• 92. Fujioka M, Kanzaki S, Okano HJ, Masuda M, Ogawa K, Okano H. Proinflammatory cytokines expression in noise-induced damaged cochlea. J. Neurosci. Res. 83(4), 575–583 (2006).
  Medline CASGoogle Scholar
• 93. Sziklai I, Batta TJ, Karosi T. Otosclerosis: an organ-specific inflammatory disease with sensorineural hearing loss. Eur. Arch. Otorhinolaryngol. 266(11), 1711–1718 (2009).
  MedlineGoogle Scholar
• 94. Moon SK, Woo JI, Lim DJ. Involvement of TNF-α and IFN-γ in inflammation-mediated cochlear injury. Ann. Otol. Rhinol. Laryngol. 128(Suppl. 6), S8–S15 (2019).
  Google Scholar
• 95. Yang X, Merchant MS, Romero ME et al. Induction of caspase 8 by interferon γ renders some neuroblastoma (NB) cells sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but reveals that a lack of membrane TR1/TR2 also contributes to TRAIL resistance in NB. Cancer Res. 63(5), 1122–1129 (2003).
  Medline CASGoogle Scholar
• 96. Young IS, Woodside JV. Antioxidants in health and disease. J. Clin. Pathol. 54(3), 176–186 (2001).
  Medline CASGoogle Scholar