Skip to main content
Top
Published in: European Archives of Oto-Rhino-Laryngology 10/2005

01-10-2005 | Otology

The protective effect of erdosteine against ototoxicity induced by cisplatin in rats

Authors: M. Tayyar Kalcioglu, Ahmet Kizilay, Mukaddes Gulec, Erkan Karatas, Mustafa Iraz, Omer Akyol, Mucahit Egri, Orhan Ozturan

Published in: European Archives of Oto-Rhino-Laryngology | Issue 10/2005

Login to get access

Abstract

The elimination of cisplatin ototoxicity is an ongoing concern. This experimental study was undertaken to investigate the effect of oral erdosteine in ameliorating cisplatin-induced ototoxicity. Twenty-eight adult female Wistar albino rats were randomly divided into four equal groups. Group A received an oral carrier vehicle of the drug erdosteine with 0.2 ml of 0.9% saline. Group B was administered only erdosteine (per oral 10 mg/kg twice a day) for 6 days. Group C was injected with cisplatin intraperitoneally (i.p.) on day 0 (16 mg/kg body weight), once only. Group D was given erdosteine (per oral 10 mg/kg/day) 1 day before and for 5 days consecutively after cisplatin injection (16 mg/kg, i.p.). Distortion product otoacoustic emissions (DPOAEs) were elicited in different frequency regions, ranging from 1,001 to 6,299 Hz as DPgram and input/output (I/O) functions from the control and experimental animals. All experimental animals were killed under general anesthesia on day 5, following the last otoacoustic emission measurements. Prior to death, blood samples were drawn for measurement of superoxide dismutase, xanthine oxidase (XO), malondialdehyde and nitric oxide. Initial DPgram and I/O function baseline measurements were similar in all groups prior to any drug administration ( P>0.05). On day 5, intra-subject measurement parameters of DPgrams and I/O functions in the cisplatin group showed significant deterioration ( P <0.05). The other groups revealed no differences between their pre- and post-test drug administration DPgrams and I/O functions at any test frequency ( P>0.05). Comparison of the amplitudes of DPgrams and I/O functions between the cisplatin and control groups showed significant changes ( P <0.05). Biochemical studies noted an increased XO activity following cisplatin administration ( P <0.007). The other biochemical results did not show significant differences between the study and control groups. This study demonstrates that, in rats, erdosteine is protective for cochlear function against the disruptive effects of cisplatin as measured by DPOAEs.
Literature
1.
go back to reference Biagi GL, Fregnan GB, Gazzani G, Vandoni G (1989) Erdosteine protection from cigarette smoke-induced loss of alpha 1-antitrypsin activity in rat lungs. Int J Clin Pharmacol Ther Toxicol 27:235–237 Biagi GL, Fregnan GB, Gazzani G, Vandoni G (1989) Erdosteine protection from cigarette smoke-induced loss of alpha 1-antitrypsin activity in rat lungs. Int J Clin Pharmacol Ther Toxicol 27:235–237
2.
go back to reference Blakley BW, Gupta AK, Myers SF, Schwan S (1994) Risck factor for ototoxicity due to cisplatin. Arch Otolaryngol Head Neck Surg 120:541–546 Blakley BW, Gupta AK, Myers SF, Schwan S (1994) Risck factor for ototoxicity due to cisplatin. Arch Otolaryngol Head Neck Surg 120:541–546
3.
go back to reference Braga PC, Dal Sasso M, Zuccotti T (2000) Assessment of the antioxidant activity of the SH metabolite I of erdosteine on human neutrophil oxidative bursts. Arzneimittelforschung 50:739–746 Braga PC, Dal Sasso M, Zuccotti T (2000) Assessment of the antioxidant activity of the SH metabolite I of erdosteine on human neutrophil oxidative bursts. Arzneimittelforschung 50:739–746
4.
go back to reference Campbell KC, Rybak LP, Meech RP, Hughes L (1996) D-methionine provides excellent protection from cisplatin ototoxicity in the rat. Hear Res 102:90–98 Campbell KC, Rybak LP, Meech RP, Hughes L (1996) D-methionine provides excellent protection from cisplatin ototoxicity in the rat. Hear Res 102:90–98
5.
go back to reference Campbell KC, Meech RP, Rybak LP, Hughes LF (2003) The effect of D-methionine on cochlear oxidative state with and without cisplatin administration: mechanisms of otoprotection. J Am Acad Audiol 14:144–156 Campbell KC, Meech RP, Rybak LP, Hughes LF (2003) The effect of D-methionine on cochlear oxidative state with and without cisplatin administration: mechanisms of otoprotection. J Am Acad Audiol 14:144–156
6.
go back to reference Clerici WJ, Hensley K, DiMartino DL, Butterfield DA (1996) Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res 98:116–124 Clerici WJ, Hensley K, DiMartino DL, Butterfield DA (1996) Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res 98:116–124
7.
go back to reference Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 36:1440–1443 Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 36:1440–1443
8.
go back to reference Dechant KL, Noble S (1996) Erdosteine. Drugs 52:875–881 Dechant KL, Noble S (1996) Erdosteine. Drugs 52:875–881
9.
go back to reference de Jongh FE, van Veen RN, Veltman SJ, de Wit R, van der Burg ME, van den Bent MJ, Planting AS, Graveland WJ, Stoter G, Verweij J (2003) Weekly high-dose cisplatin in a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients. Br J Cancer 88:1199–1206 de Jongh FE, van Veen RN, Veltman SJ, de Wit R, van der Burg ME, van den Bent MJ, Planting AS, Graveland WJ, Stoter G, Verweij J (2003) Weekly high-dose cisplatin in a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients. Br J Cancer 88:1199–1206
10.
go back to reference Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421CrossRefPubMed Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421CrossRefPubMed
11.
go back to reference Fadillioglu E, Erdogan H (2003) Effects of erdosteine treatment against doxorubicin-induced toxicity through erythrocyte and plasma oxidant/antioxidant status in rats. Pharmacol Res 47:317–322 Fadillioglu E, Erdogan H (2003) Effects of erdosteine treatment against doxorubicin-induced toxicity through erythrocyte and plasma oxidant/antioxidant status in rats. Pharmacol Res 47:317–322
12.
go back to reference Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, Bagby GC Jr (1993) High-frequency monitoring for early detection of cisplatin ototoxicity. Arch Otolaryngol Head Neck Surg 119:661–666 Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, Bagby GC Jr (1993) High-frequency monitoring for early detection of cisplatin ototoxicity. Arch Otolaryngol Head Neck Surg 119:661–666
13.
go back to reference Gazzani G, Fregnan GB, Vandoni G (1989) In vitro protection by erdosteine against oxidative inactivation of alpha-1-antitrypsin by cigarette smoke. Respiration 55:113–118 Gazzani G, Fregnan GB, Vandoni G (1989) In vitro protection by erdosteine against oxidative inactivation of alpha-1-antitrypsin by cigarette smoke. Respiration 55:113–118
14.
go back to reference Huang T, Cheng AG, Stupak H, Liu W, Kim A, Staecker H, Lefebvre PP, Malgrange B, Kopke R, Moonen G, Van de Water TR (2000) Oxidative stress-induced apoptosis of cochlear sensory cells: otoprotective strategies. Int J Dev Neurosci 18:259–270 Huang T, Cheng AG, Stupak H, Liu W, Kim A, Staecker H, Lefebvre PP, Malgrange B, Kopke R, Moonen G, Van de Water TR (2000) Oxidative stress-induced apoptosis of cochlear sensory cells: otoprotective strategies. Int J Dev Neurosci 18:259–270
15.
go back to reference Inglesi M, Nicola M, Fregnan GB, Bradamante S, Pagani G (1994) Synthesis and free radical scavenging properties of the enantiomers of erdosteine. Farmaco 40:703–708 Inglesi M, Nicola M, Fregnan GB, Bradamante S, Pagani G (1994) Synthesis and free radical scavenging properties of the enantiomers of erdosteine. Farmaco 40:703–708
16.
go back to reference Irmak MK, Koltuksuz U, Kutlu NO, Yagmurca M, Ozyurt H, Karaman A, Akyol O (2001) The effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in comparison with α-tocopherol in rat kidneys. Urol Res 29:190–193 Irmak MK, Koltuksuz U, Kutlu NO, Yagmurca M, Ozyurt H, Karaman A, Akyol O (2001) The effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in comparison with α-tocopherol in rat kidneys. Urol Res 29:190–193
17.
go back to reference Koltuksuz U, Irmak MK, Karaman A, Uz E, Var A, Ozyurt H, Akyol O (2000) Testicular nitric oxide levels after unilateral testicular torsion/detorsion in rats pretreated with caffeic acid phenethyl ester. Urol Res 28:360–363 Koltuksuz U, Irmak MK, Karaman A, Uz E, Var A, Ozyurt H, Akyol O (2000) Testicular nitric oxide levels after unilateral testicular torsion/detorsion in rats pretreated with caffeic acid phenethyl ester. Urol Res 28:360–363
18.
go back to reference Kopke RD, Liu W, Gabaizadeh R, Jacono A, Feghali J, Sprat D, Garcia P, Steinman H, Malgrange B, Ruben RJ, Rybak L, Van de Water TR (1997) Use of organotypic cultures of Corti’s organ to study the protective effects of antioxidant molecules on cisplatin-induced damage of auditory hair cells. Am J Otol 18:559–571 Kopke RD, Liu W, Gabaizadeh R, Jacono A, Feghali J, Sprat D, Garcia P, Steinman H, Malgrange B, Ruben RJ, Rybak L, Van de Water TR (1997) Use of organotypic cultures of Corti’s organ to study the protective effects of antioxidant molecules on cisplatin-induced damage of auditory hair cells. Am J Otol 18:559–571
19.
go back to reference Lopez-Gonzalez MA, Guerrero JM, Rojas F, Delgado F (2000) Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res 28:73–80 Lopez-Gonzalez MA, Guerrero JM, Rojas F, Delgado F (2000) Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res 28:73–80
20.
go back to reference Miyake K, Kaise T, Hosoe H, Akuta K, Manabe H, Ohmori K (1999) The effect of erdosteine and its reactive metabolite on reactive oxygen species production by inflammatory cells. Inflamm Res 48:205–209 Miyake K, Kaise T, Hosoe H, Akuta K, Manabe H, Ohmori K (1999) The effect of erdosteine and its reactive metabolite on reactive oxygen species production by inflammatory cells. Inflamm Res 48:205–209
21.
go back to reference Ozturan O, Jerger J, Lew H, Lynch GR (1996) Monitoring of cisplatin ototoxicity by distortion-product otoacoustic emissions. Auris Nasus Larynx 23:147–151 Ozturan O, Jerger J, Lew H, Lynch GR (1996) Monitoring of cisplatin ototoxicity by distortion-product otoacoustic emissions. Auris Nasus Larynx 23:147–151
22.
go back to reference Prajda N, Weber G (1975) Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas. FEBS Lett 59:245–249 Prajda N, Weber G (1975) Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas. FEBS Lett 59:245–249
23.
go back to reference Ravi R, Somani SM, Rybak LP (1995) Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol 76:386–394 Ravi R, Somani SM, Rybak LP (1995) Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol 76:386–394
24.
go back to reference Rybak LP, Kelly T (2003) Ototoxicity: bioprotective mechanisms. Curr Opin Otolaryngol Head Neck Surg 11:328–333 Rybak LP, Kelly T (2003) Ototoxicity: bioprotective mechanisms. Curr Opin Otolaryngol Head Neck Surg 11:328–333
25.
go back to reference Sakamoto M, Kaga K, Kamio T (2000) Extended high-frequency ototoxicity induced by the first administration of cisplatin. Otolaryngol Head Neck Surg 122:828–833 Sakamoto M, Kaga K, Kamio T (2000) Extended high-frequency ototoxicity induced by the first administration of cisplatin. Otolaryngol Head Neck Surg 122:828–833
26.
go back to reference Sogut S, Zoroglu SS, Ozyurt H, Yilmaz HR, Ozugurlu F, Sivasli E, Yetkin O, Yanik M, Tutkun H, Savas HA, Tarakcioglu M (2003) Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta 331:111–117 Sogut S, Zoroglu SS, Ozyurt H, Yilmaz HR, Ozugurlu F, Sivasli E, Yetkin O, Yanik M, Tutkun H, Savas HA, Tarakcioglu M (2003) Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta 331:111–117
27.
go back to reference Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500PubMed Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500PubMed
28.
go back to reference Vagliasindi M, Fregnan GB (1989) Erdosteine protection against cigarette smoking-induced functional antiprotease deficiency in human bronchiolo-alveolar structures. Int J Clin Pharmacol Ther Toxicol 27:238–241 Vagliasindi M, Fregnan GB (1989) Erdosteine protection against cigarette smoking-induced functional antiprotease deficiency in human bronchiolo-alveolar structures. Int J Clin Pharmacol Ther Toxicol 27:238–241
29.
go back to reference Weijl NI, Elsendoorn TJ, Lentjes EG, Hopman GD, Wipkink-Bakker A, Zwinderman AH, Cleton FJ, Osanto S (2004) Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. Eur J Cancer 40:1713–1723 Weijl NI, Elsendoorn TJ, Lentjes EG, Hopman GD, Wipkink-Bakker A, Zwinderman AH, Cleton FJ, Osanto S (2004) Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. Eur J Cancer 40:1713–1723
30.
go back to reference Wimmer C, Mees K, Stumpf P, Welsch U, Reichel O, Suckfull M (2004) Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity. Otol Neurotol 25:33–40 Wimmer C, Mees K, Stumpf P, Welsch U, Reichel O, Suckfull M (2004) Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity. Otol Neurotol 25:33–40
31.
go back to reference Yildirim Z, Sogut S, Odaci E, Iraz M, Ozyurt H, Kotuk M, Akyol O (2003) Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats. Pharmacol Res 47:149–156 Yildirim Z, Sogut S, Odaci E, Iraz M, Ozyurt H, Kotuk M, Akyol O (2003) Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats. Pharmacol Res 47:149–156
Metadata
Title
The protective effect of erdosteine against ototoxicity induced by cisplatin in rats
Authors
M. Tayyar Kalcioglu
Ahmet Kizilay
Mukaddes Gulec
Erkan Karatas
Mustafa Iraz
Omer Akyol
Mucahit Egri
Orhan Ozturan
Publication date
01-10-2005
Publisher
Springer-Verlag
Published in
European Archives of Oto-Rhino-Laryngology / Issue 10/2005
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-004-0909-7

Other articles of this Issue 10/2005

European Archives of Oto-Rhino-Laryngology 10/2005 Go to the issue