The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans

Summary

The proposal of this study was to evaluate in human beings, using distortion product otoacoustic emission (DPOAE) test, the action of ginkgo biloba extract (GBE761)as a possible ear protective against cisplatin (CDDP) induced hearing loss.

Timeline

Start

2007-06

Primary completion

2008-06

Completion

2008-06

Publications

• Background Biro K, Noszek L, Prekopp P, Nagyivanyi K, Geczi L, Gaudi I, Bodrogi I. Characteristics and risk factors of cisplatin-induced ototoxicity in testicular cancer patients detected by distortion product otoacoustic emission. Oncology. 2006;70(3):177-84. doi: 10.1159/000093776. Epub 2006 Jun 2.
• Background Blakley BW, Myers SF. Patterns of hearing loss resulting from cis-platinum therapy. Otolaryngol Head Neck Surg. 1993 Sep;109(3 Pt 1):385-91. doi: 10.1177/019459989310900302.
• Background Bridi R, Crossetti FP, Steffen VM, Henriques AT. The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats. Phytother Res. 2001 Aug;15(5):449-51. doi: 10.1002/ptr.814.
• Background Christen Y, Maixent JM. What is Ginkgo biloba extract EGb 761? An overview--from molecular biology to clinical medicine. Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):601-11.
• Background Dhooge I, Dhooge C, Geukens S, De Clerck B, De Vel E, Vinck BM. Distortion product otoacoustic emissions: an objective technique for the screening of hearing loss in children treated with platin derivatives. Int J Audiol. 2006 Jun;45(6):337-43. doi: 10.1080/14992020600582117.
• Background Gardner CD, Zehnder JL, Rigby AJ, Nicholus JR, Farquhar JW. Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial. Blood Coagul Fibrinolysis. 2007 Dec;18(8):787-93. doi: 10.1097/MBC.0b013e3282f102b1.
• Background Gorga MP, Neely ST, Ohlrich B, Hoover B, Redner J, Peters J. From laboratory to clinic: a large scale study of distortion product otoacoustic emissions in ears with normal hearing and ears with hearing loss. Ear Hear. 1997 Dec;18(6):440-55. doi: 10.1097/00003446-199712000-00003.
• Background Gorga MP, Stover L, Neely ST, Montoya D. The use of cumulative distributions to determine critical values and levels of confidence for clinical distortion product otoacoustic emission measurements. J Acoust Soc Am. 1996 Aug;100(2 Pt 1):968-77. doi: 10.1121/1.416208.
• Background Hatzopoulos S, Di Stefano M, Campbell KC, Falgione D, Ricci D, Rosignoli M, Finesso M, Albertin A, Previati M, Capitani S, Martini A. Cisplatin ototoxicity in the Sprague Dawley rat evaluated by distortion product otoacoustic emissions. Audiology. 2001 Sep-Oct;40(5):253-64.
• Background Hibatallah J, Carduner C, Poelman MC. In-vivo and in-vitro assessment of the free-radical-scavenger activity of Ginkgo flavone glycosides at high concentration. J Pharm Pharmacol. 1999 Dec;51(12):1435-40. doi: 10.1211/0022357991777083.
• Background Huang T, Cheng AG, Stupak H, Liu W, Kim A, Staecker H, Lefebvre PP, Malgrange B, Kopke R, Moonen G, Van De Water TR. Oxidative stress-induced apoptosis of cochlear sensory cells: otoprotective strategies. Int J Dev Neurosci. 2000 Apr-Jun;18(2-3):259-70. doi: 10.1016/s0736-5748(99)00094-5.
• Background Rybak LP, Husain K, Morris C, Whitworth C, Somani S. Effect of protective agents against cisplatin ototoxicity. Am J Otol. 2000 Jul;21(4):513-20.
• Background Kaltenbach JA, Church MW, Blakley BW, McCaslin DL, Burgio DL. Comparison of five agents in protecting the cochlea against the ototoxic effects of cisplatin in the hamster. Otolaryngol Head Neck Surg. 1997 Nov;117(5):493-500. doi: 10.1016/S0194-59989770020-2.
• Background Kobuchi H, Droy-Lefaix MT, Christen Y, Packer L. Ginkgo biloba extract (EGb 761): inhibitory effect on nitric oxide production in the macrophage cell line RAW 264.7. Biochem Pharmacol. 1997 Mar 21;53(6):897-903. doi: 10.1016/s0006-2952(96)00873-8.
• Background Meyerhoff WL, Maale GE, Yellin W, Roland PS. Audiologic threshold monitoring of patients receiving ototoxic drugs. Preliminary report. Ann Otol Rhinol Laryngol. 1989 Dec;98(12 Pt 1):950-4. doi: 10.1177/000348948909801206.
• Background Palomar Garcia V, Abdulghani Martinez F, Bodet Agusti E, Andreu Mencia L, Palomar Asenjo V. Drug-induced otoxicity: current status. Acta Otolaryngol. 2001 Jul;121(5):569-72. doi: 10.1080/00016480121545.
• Background Campbell K. Ototoxicity: understanding oxidative mechanisms. J Am Acad Audiol. 2003 Apr;14(3):121-3. doi: 10.3766/jaaa.14.3.2. No abstract available.
• Background Campbell KC, Durrant J. Audiologic monitoring for ototoxicity. Otolaryngol Clin North Am. 1993 Oct;26(5):903-14.
• Background Diamond BJ, Shiflett SC, Feiwel N, Matheis RJ, Noskin O, Richards JA, Schoenberger NE. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil. 2000 May;81(5):668-78. doi: 10.1016/s0003-9993(00)90052-2.
• Background Franklin DJ, McCoy MJ, Martin GK, Lonsbury-Martin BL. Test/retest reliability of distortion-product and transiently evoked otoacoustic emissions. Ear Hear. 1992 Dec;13(6):417-29. doi: 10.1097/00003446-199212000-00008.
• Background Bonfils P, Avan P. Distortion-product otoacoustic emissions. Values for clinical use. Arch Otolaryngol Head Neck Surg. 1992 Oct;118(10):1069-76. doi: 10.1001/archotol.1992.01880100061014.
• Background Kemp DT, Ryan S, Bray P. A guide to the effective use of otoacoustic emissions. Ear Hear. 1990 Apr;11(2):93-105. doi: 10.1097/00003446-199004000-00004.
• Background Kimberley BP. Applications of distortion-product emissions to an otological practice. Laryngoscope. 1999 Dec;109(12):1908-18. doi: 10.1097/00005537-199912000-00003.
• Background Knight KR, Kraemer DF, Winter C, Neuwelt EA. Early changes in auditory function as a result of platinum chemotherapy: use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions. J Clin Oncol. 2007 Apr 1;25(10):1190-5. doi: 10.1200/JCO.2006.07.9723.
• Background Komune S, Asakuma S, Snow JB Jr. Pathophysiology of the ototoxicity of cis-diamminedichloroplatinum. Otolaryngol Head Neck Surg. 1981 Mar-Apr;89(2):275-82. doi: 10.1177/019459988108900226.
• Background Kushner BH, Budnick A, Kramer K, Modak S, Cheung NK. Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma. Cancer. 2006 Jul 15;107(2):417-22. doi: 10.1002/cncr.22004.
• Background Laurell G, Bagger-Sjoback D. Dose-dependent inner ear changes after i.v. administration of cisplatin. J Otolaryngol. 1991 Jun;20(3):158-67.
• Background Le Bars PL, Kastelan J. Efficacy and safety of a Ginkgo biloba extract. Public Health Nutr. 2000 Dec;3(4A):495-9. doi: 10.1017/s1368980000000574.
• Background Lonsbury-Martin BL, Whitehead ML, Martin GK. Clinical applications of otoacoustic emissions. J Speech Hear Res. 1991 Oct;34(5):964-81. doi: 10.1044/jshr.3405.964.
• Background Mahadevan S, Park Y. Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses. J Food Sci. 2008 Jan;73(1):R14-9. doi: 10.1111/j.1750-3841.2007.00597.x.
• Background Maitra I, Marcocci L, Droy-Lefaix MT, Packer L. Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761. Biochem Pharmacol. 1995 May 26;49(11):1649-55. doi: 10.1016/0006-2952(95)00089-i.
• Background Marcocci L, Packer L, Droy-Lefaix MT, Sekaki A, Gardes-Albert M. Antioxidant action of Ginkgo biloba extract EGb 761. Methods Enzymol. 1994;234:462-75. doi: 10.1016/0076-6879(94)34117-6. No abstract available.
• Background McKenna DJ, Jones K, Hughes K. Efficacy, safety, and use of ginkgo biloba in clinical and preclinical applications. Altern Ther Health Med. 2001 Sep-Oct;7(5):70-86, 88-90.
• Background Ohlms LA, Lonsbury-Martin BL, Martin GK. The clinical application of acoustic distortion products. Otolaryngol Head Neck Surg. 1990 Jul;103(1):52-9. doi: 10.1177/019459989010300108.
• Background Ozturan O, Jerger J, Lew H, Lynch GR. Monitoring of cisplatin ototoxicity by distortion-product otoacoustic emissions. Auris Nasus Larynx. 1996;23:147-51. doi: 10.1016/s0385-8146(96)80023-x.
• Background Pincemail J, Dupuis M, Nasr C, Hans P, Haag-Berrurier M, Anton R, Deby C. Superoxide anion scavenging effect and superoxide dismutase activity of Ginkgo biloba extract. Experientia. 1989 Aug 15;45(8):708-12. doi: 10.1007/BF01974564.
• Background Probst R, Hauser R. Distortion product otoacoustic emissions in normal and hearing-impaired ears. Am J Otolaryngol. 1990 Jul-Aug;11(4):236-43. doi: 10.1016/0196-0709(90)90083-8.
• Background Ravi R, Somani SM, Rybak LP. Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol. 1995 Jun;76(6):386-94. doi: 10.1111/j.1600-0773.1995.tb00167.x.
• Background Rademaker-Lakhai JM, Crul M, Zuur L, Baas P, Beijnen JH, Simis YJ, van Zandwijk N, Schellens JH. Relationship between cisplatin administration and the development of ototoxicity. J Clin Oncol. 2006 Feb 20;24(6):918-24. doi: 10.1200/JCO.2006.10.077.
• Background Ress BD, Sridhar KS, Balkany TJ, Waxman GM, Stagner BB, Lonsbury-Martin BL. Effects of cis-platinum chemotherapy on otoacoustic emissions: the development of an objective screening protocol. Third place--Resident Clinical Science Award 1998. Otolaryngol Head Neck Surg. 1999 Dec;121(6):693-701. doi: 10.1053/hn.1999.v121.a101567.
• Background Rybak LP, Kelly T. Ototoxicity: bioprotective mechanisms. Curr Opin Otolaryngol Head Neck Surg. 2003 Oct;11(5):328-33. doi: 10.1097/00020840-200310000-00004.
• Background Rybak LP. Mechanisms of cisplatin ototoxicity and progress in otoprotection. Curr Opin Otolaryngol Head Neck Surg. 2007 Oct;15(5):364-9. doi: 10.1097/MOO.0b013e3282eee452.
• Background Rybak LP, Whitworth CA, Mukherjea D, Ramkumar V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res. 2007 Apr;226(1-2):157-67. doi: 10.1016/j.heares.2006.09.015. Epub 2006 Nov 17.
• Background Rybak LP, Whitworth C, Somani S. Application of antioxidants and other agents to prevent cisplatin ototoxicity. Laryngoscope. 1999 Nov;109(11):1740-4. doi: 10.1097/00005537-199911000-00003.
• Background Rybak LP, Ramkumar V. Ototoxicity. Kidney Int. 2007 Oct;72(8):931-5. doi: 10.1038/sj.ki.5002434. Epub 2007 Jul 25.
• Background Rybak LP, Whitworth CA. Ototoxicity: therapeutic opportunities. Drug Discov Today. 2005 Oct 1;10(19):1313-21. doi: 10.1016/S1359-6446(05)03552-X.
• Background Sie KC, Norton SJ. Changes in otoacoustic emissions and auditory brain stem response after cis-platinum exposure in gerbils. Otolaryngol Head Neck Surg. 1997 Jun;116(6 Pt 1):585-92. doi: 10.1016/S0194-59989770232-8.
• Background Singh B, Kaur P, Gopichand, Singh RD, Ahuja PS. Biology and chemistry of Ginkgo biloba. Fitoterapia. 2008 Sep;79(6):401-18. doi: 10.1016/j.fitote.2008.05.007. Epub 2008 Jun 27.
• Background Stavroulaki P, Apostolopoulos N, Segas J, Tsakanikos M, Adamopoulos G. Evoked otoacoustic emissions--an approach for monitoring cisplatin induced ototoxicity in children. Int J Pediatr Otorhinolaryngol. 2001 May 31;59(1):47-57. doi: 10.1016/s0165-5876(01)00455-4.
• Background Stover L, Gorga MP, Neely ST, Montoya D. Toward optimizing the clinical utility of distortion product otoacoustic emission measurements. J Acoust Soc Am. 1996 Aug;100(2 Pt 1):956-67. doi: 10.1121/1.416207.
• Background Toral-Martinon R, Shkurovich-Bialik P, Collado-Corona MA, Mora-Magana I, Goldgrub-Listopad S, Shkurovich-Zaslavsky M. Distortion product otoacoustic emissions test is useful in children undergoing cisplatin treatment. Arch Med Res. 2003 May-Jun;34(3):205-8. doi: 10.1016/S0188-4409(03)00022-5.
• Background Vermorken JB, Kapteijn TS, Hart AA, Pinedo HM. Ototoxicity of cis-diamminedichloroplatinum (II): influence of dose, schedule and mode of administration. Eur J Cancer Clin Oncol. 1983 Jan;19(1):53-8. doi: 10.1016/0277-5379(83)90398-x.
• Background Zorowka PG, Schmitt HJ, Gutjahr P. Evoked otoacoustic emissions and pure tone threshold audiometry in patients receiving cisplatinum therapy. Int J Pediatr Otorhinolaryngol. 1993 Jan;25(1-3):73-80. doi: 10.1016/0165-5876(93)90011-q.
• Background Sockalingam R, Freeman S, Cherny TL, Sohmer H. Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals. Am J Otol. 2000 Jul;21(4):521-7.
• Results Fukaya H, Kanno H. [Experimental studies of the protective effect of ginkgo biloba extract (GBE) on cisplatin-induced toxicity in rats]. Nihon Jibiinkoka Gakkai Kaiho. 1999 Jul;102(7):907-17. doi: 10.3950/jibiinkoka.102.907. Japanese.
• Results Huang X, Whitworth CA, Rybak LP. Ginkgo biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in rats. Otol Neurotol. 2007 Sep;28(6):828-33. doi: 10.1097/mao.0b013e3180430163.

Drugs

Indications