Skip to main content
Top
Published in: European Archives of Oto-Rhino-Laryngology 8/2013

01-08-2013 | Otology

Protective effect of thymoquinone against cisplatin-induced ototoxicity

Authors: Mustafa Sagit, Ferhat Korkmaz, Alper Akcadag, Mehmet Akıf Somdas

Published in: European Archives of Oto-Rhino-Laryngology | Issue 8/2013

Login to get access

Abstract

The aim of this study was to investigate the potential protective effect of thymoquinone against cisplatin-induced ototoxicity. This study is a prospective, controlled experimental animal study. Experiments were performed on 30 healthy female Sprague-Dawley rats. Thirty animals were divided into three groups of 10 animals each. Group 1 received an intraperitoneal (i.p.) injection of cisplatin 15 mg/kg. Group 2 received i.p. thymoquinone 40 mg/kg/day for 2 days prior to cisplatin injection and third day i.p. cisplatin 15 mg/kg was administered concomitantly. Group 2 continued to receive i.p. thymoquinone until fifth day. Group 3 received i.p. thymoquinone 40 mg/kg/day for 5 days. Pretreatment distortion product otoacoustic emissions (DPOAE) and auditory brain stem responses (ABR) testing from both ears were obtained from the animals in all groups. After the baseline measurements, drugs were injected intraperitonally. After an observation period of 3 days, DPOAE measurements and ABR testing were obtained again and compared with the pretreatment values. There was no statistically significant difference between pre and post-treatment DPOAE responses and ABR thresholds group 2 and 3. However, group 1 demonstrated significant deterioration of the ABR thresholds and DPOAE responses. Our results suggest that DPOAE responses and ABR thresholds were preserved in the cisplatin plus TQ-treated group when compared with the group receiving cisplatin alone. According to these results, cisplatin-induced ototoxicity may be prevented by thymoquinone use in rats.
Literature
1.
go back to reference Rybak LP, Mukherjea D, Jajoo S, Ramkumar V (2009) Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med 219:177–186PubMedCrossRef Rybak LP, Mukherjea D, Jajoo S, Ramkumar V (2009) Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med 219:177–186PubMedCrossRef
2.
3.
4.
go back to reference Yumusakhuylu AC, Yazici M, Sari M, Binnetoglu A, Kosemihal E, Akdas F, Sirvanci S, Yuksel M, Uneri C, Tutkun A (2012) Protective role of resveratrol against cisplatin induced ototoxicity in guinea pigs. Int J Pediatr Otorhinolaryngol 76:404–408PubMedCrossRef Yumusakhuylu AC, Yazici M, Sari M, Binnetoglu A, Kosemihal E, Akdas F, Sirvanci S, Yuksel M, Uneri C, Tutkun A (2012) Protective role of resveratrol against cisplatin induced ototoxicity in guinea pigs. Int J Pediatr Otorhinolaryngol 76:404–408PubMedCrossRef
5.
go back to reference Erdem T, Bayindir T, Filiz A, Iraz M, Selimoglu E (2011) The effect of resveratrol on the prevention of cisplatin ototoxicity. Eur Arch Otorhinolaryngol 269:2185–2188PubMedCrossRef Erdem T, Bayindir T, Filiz A, Iraz M, Selimoglu E (2011) The effect of resveratrol on the prevention of cisplatin ototoxicity. Eur Arch Otorhinolaryngol 269:2185–2188PubMedCrossRef
6.
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 28:73–80PubMedCrossRef Lopez-Gonzalez MA, Guerrero JM, Rojas F, Delgado F (2000) Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res 28:73–80PubMedCrossRef
7.
go back to reference Daldal A, Odabasi O, Serbetcioglu B (2007) The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs. Otolaryngol Head Neck Surg 137:747–752PubMedCrossRef Daldal A, Odabasi O, Serbetcioglu B (2007) The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs. Otolaryngol Head Neck Surg 137:747–752PubMedCrossRef
8.
go back to reference Kalkanis JG, Whitworth C, Rybak LP (2004) Vitamin E reduces cisplatin ototoxicity. Laryngoscope 114:538–542PubMedCrossRef Kalkanis JG, Whitworth C, Rybak LP (2004) Vitamin E reduces cisplatin ototoxicity. Laryngoscope 114:538–542PubMedCrossRef
9.
go back to reference Campbell KC, Meech RP, Rybak LP, Hughes LF (1999) d-Methionine protects against cisplatin damage to the stria vascularis. Hear Res 138:13–28PubMedCrossRef Campbell KC, Meech RP, Rybak LP, Hughes LF (1999) d-Methionine protects against cisplatin damage to the stria vascularis. Hear Res 138:13–28PubMedCrossRef
10.
go back to reference Feghali JG, Liu W, Van De Water TR (2001) L-n-acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope 111:1147–1155PubMedCrossRef Feghali JG, Liu W, Van De Water TR (2001) L-n-acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope 111:1147–1155PubMedCrossRef
11.
go back to reference Huang X, Whitworth CA, Rybak LP (2007) Ginkgo biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in rats. Otol Neurotol 28:828–833PubMedCrossRef Huang X, Whitworth CA, Rybak LP (2007) Ginkgo biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in rats. Otol Neurotol 28:828–833PubMedCrossRef
12.
go back to reference Lynch ED, Gu R, Pierce C, Kil J (2005) Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen. Hear Res 201:81–89PubMedCrossRef Lynch ED, Gu R, Pierce C, Kil J (2005) Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen. Hear Res 201:81–89PubMedCrossRef
13.
go back to reference Church MW, Blakley BW, Burgio DL, Gupta AK (2004) WR-2721 (Amifostine) ameliorates cisplatin-induced hearing loss but causes neurotoxicity in hamsters: dose-dependent effects. J Assoc Res Otolaryngol 5:227–237PubMedCrossRef Church MW, Blakley BW, Burgio DL, Gupta AK (2004) WR-2721 (Amifostine) ameliorates cisplatin-induced hearing loss but causes neurotoxicity in hamsters: dose-dependent effects. J Assoc Res Otolaryngol 5:227–237PubMedCrossRef
14.
go back to reference Hyppolito MA, de Oliveira JA, Rossato M (2006) Cisplatin ototoxicity and otoprotection with sodium salicylate. Eur Arch Otorhinolaryngol 263:798–803PubMedCrossRef Hyppolito MA, de Oliveira JA, Rossato M (2006) Cisplatin ototoxicity and otoprotection with sodium salicylate. Eur Arch Otorhinolaryngol 263:798–803PubMedCrossRef
15.
go back to reference Xu O, Liu Y, Li X, Yang Y, Zhang Z, Wang N, Zhang Y, Lu H (2011) Protective effects of Salvia miltiorrhiza against cisplatin-induced ototoxicity in guinea pigs. Am J Otolaryngol 32:228–234PubMedCrossRef Xu O, Liu Y, Li X, Yang Y, Zhang Z, Wang N, Zhang Y, Lu H (2011) Protective effects of Salvia miltiorrhiza against cisplatin-induced ototoxicity in guinea pigs. Am J Otolaryngol 32:228–234PubMedCrossRef
16.
go back to reference Yazici ZM, Meric A, Midi A, Arınc YV, Kahya V, Hafız G (2012) Reduction of cisplatin ototoxicity in rats by oral administration of pomegranate extract. Eur Arch Otorhinolaryngol 269:45–52PubMedCrossRef Yazici ZM, Meric A, Midi A, Arınc YV, Kahya V, Hafız G (2012) Reduction of cisplatin ototoxicity in rats by oral administration of pomegranate extract. Eur Arch Otorhinolaryngol 269:45–52PubMedCrossRef
17.
go back to reference Gökçe A, Oktar S, Koc A, Yonden Z (2011) Protective effects of thymoquinone against methotrexate-induced testicular injury. Hum Exp Toxicol 30:897–903PubMedCrossRef Gökçe A, Oktar S, Koc A, Yonden Z (2011) Protective effects of thymoquinone against methotrexate-induced testicular injury. Hum Exp Toxicol 30:897–903PubMedCrossRef
18.
go back to reference Basarslan F, Yilmaz N, Ates S, Ozgur T, Tutanc M, Motor VK, Arica V, Yilmaz C, Inci M, Buyukbas S (2012) Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats. Hum Exp Toxicol 16:E167–E171 Basarslan F, Yilmaz N, Ates S, Ozgur T, Tutanc M, Motor VK, Arica V, Yilmaz C, Inci M, Buyukbas S (2012) Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats. Hum Exp Toxicol 16:E167–E171
19.
go back to reference Nader MA, el-Agamy DS, Suddek GM (2010) Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharm Res 33:637–643PubMedCrossRef Nader MA, el-Agamy DS, Suddek GM (2010) Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharm Res 33:637–643PubMedCrossRef
20.
go back to reference Badary OA, Nagi MN, Al-Shabanah OA, Al-Sawaf HA, Al-Sohaibani MO, Al-Bekairi AM (1997) Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can J Physiol Pharmacol 75:1356–1361PubMedCrossRef Badary OA, Nagi MN, Al-Shabanah OA, Al-Sawaf HA, Al-Sohaibani MO, Al-Bekairi AM (1997) Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can J Physiol Pharmacol 75:1356–1361PubMedCrossRef
21.
go back to reference Nagi MN, Mansour MA (2000) Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 41:283–289PubMedCrossRef Nagi MN, Mansour MA (2000) Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 41:283–289PubMedCrossRef
22.
go back to reference Nagi MN, Alam K, Badary OA, Al-Shabanah OA, Al-Sawaf HA, Al-Bekairi AM (1999) Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int 47:153–159PubMed Nagi MN, Alam K, Badary OA, Al-Shabanah OA, Al-Sawaf HA, Al-Bekairi AM (1999) Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int 47:153–159PubMed
23.
go back to reference Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344:721–724PubMedCrossRef Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344:721–724PubMedCrossRef
24.
go back to reference Mansour MA, Nagi MN, El-Khatib AS, Al-Bekairi AM (2002) Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: a possible mechanism of action. Cell Biochem Funct 20:143–151PubMedCrossRef Mansour MA, Nagi MN, El-Khatib AS, Al-Bekairi AM (2002) Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: a possible mechanism of action. Cell Biochem Funct 20:143–151PubMedCrossRef
25.
go back to reference Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH et al (2003) Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 26:87–98PubMedCrossRef Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH et al (2003) Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 26:87–98PubMedCrossRef
26.
go back to reference Banerjee S, Padhye S, Azmi A, Wang Z, Philip PA, Kucuk O, Sarkar FH, Mohammad RM (2010) Review on molecular and therapeutic potential of thymoquinone in cancer. Nutr Cancer 62:938–946PubMedCrossRef Banerjee S, Padhye S, Azmi A, Wang Z, Philip PA, Kucuk O, Sarkar FH, Mohammad RM (2010) Review on molecular and therapeutic potential of thymoquinone in cancer. Nutr Cancer 62:938–946PubMedCrossRef
27.
go back to reference Woo CC, Kumar AP, Sethi G, Tan KH (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83:443–451PubMedCrossRef Woo CC, Kumar AP, Sethi G, Tan KH (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83:443–451PubMedCrossRef
28.
go back to reference Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, Sarkar FH, Mohammad RM (2009) Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res 69:5575–5583PubMedCrossRef Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, Sarkar FH, Mohammad RM (2009) Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res 69:5575–5583PubMedCrossRef
29.
go back to reference Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M, Dou QP, Reddy GP (2007) Androgen receptor and E2F–1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Res 67:7782–7788PubMedCrossRef Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M, Dou QP, Reddy GP (2007) Androgen receptor and E2F–1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Res 67:7782–7788PubMedCrossRef
30.
go back to reference Gali-Muhtasib H, Ocker M, Kuester D, Krueger S, El-Hajj Z, Diestel A, Evert M, El-Najjar N, Peters B, Jurjus A, Roessner A, Schneider-Stock R (2008) Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models. J Cell Mol Med 12:330–342PubMedCrossRef Gali-Muhtasib H, Ocker M, Kuester D, Krueger S, El-Hajj Z, Diestel A, Evert M, El-Najjar N, Peters B, Jurjus A, Roessner A, Schneider-Stock R (2008) Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models. J Cell Mol Med 12:330–342PubMedCrossRef
31.
go back to reference Jafri SH, Glass J, Shi R, Zhang S, Prince M, Kleiner-Hancock H (2010) Thymoquinone and cisplatin as a therapeutic combination in lung cancer: in vitro and in vivo. J Exp Clin Cancer Res 29:87PubMedCrossRef Jafri SH, Glass J, Shi R, Zhang S, Prince M, Kleiner-Hancock H (2010) Thymoquinone and cisplatin as a therapeutic combination in lung cancer: in vitro and in vivo. J Exp Clin Cancer Res 29:87PubMedCrossRef
Metadata
Title
Protective effect of thymoquinone against cisplatin-induced ototoxicity
Authors
Mustafa Sagit
Ferhat Korkmaz
Alper Akcadag
Mehmet Akıf Somdas
Publication date
01-08-2013
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Oto-Rhino-Laryngology / Issue 8/2013
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-012-2254-6

Other articles of this Issue 8/2013

European Archives of Oto-Rhino-Laryngology 8/2013 Go to the issue