Protective Effect of Minocycline Against Cisplatin-induced Ototoxicity
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Objectives. Cisplatin, a widely used chemotherapeutic agent, has serious side effects, including nephrotoxicity and ototoxicity. Minocycline is a semisynthetic second-generation tetracycline that exerts anti-inflammatory and neuroprotective effects. The purpose of this study was to elucidate the protective effect of minocycline against cisplatin-induced ototoxicity in the auditory hair cell. Methods. The House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line and guinea pigs were used for in vitro and in vivo experiments. Cells were exposed to cisplatin with or without pre-treatment with minocycline. Cell survival was analyzed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Whole-cell lysates were collected and immunoblotted with antibodies against Bcl-2, p-c-Jun, active caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), and apoptosis-inducing factor (AIF). The guinea pigs received intraperitoneal injections of cisplatin alone or following minocycline pretreatment. The auditory brainstem response was tested and the cochleae were harvested and evaluated using scanning electron microscopy. Results. Survival significantly increased in cells pretreated with minocycline compared with cells exposed to cisplatin alone. Cisplatin treatment increased the expression of active caspase 3, p-c Jun, PARP, and AIF, and pretreatment with minocycline attenuated this response. In animal study, the threshold shift by cisplatin injection in the auditory brainstem response was less pronounced in animals pretreated with minocycline. Scanning electron microscopy revealed more severe damage to the outer hair cells at the basal and middle turns than the apical turn. Conclusion. Minocycline partially protects against cisplatin-induced ototoxicity via both caspase-dependent and independent apoptosis pathways.
Abstract
Objectives. Cisplatin, a widely used chemotherapeutic agent, has serious side effects, including nephrotoxicity and ototoxicity. Minocycline is a semisynthetic second-generation tetracycline that exerts anti-inflammatory and neuroprotective effects. The purpose of this study was to elucidate the protective effect of minocycline against cisplatin-induced ototoxicity in the auditory hair cell. Methods. The House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line and guinea pigs were used for in vitro and in vivo experiments. Cells were exposed to cisplatin with or without pre-treatment with minocycline. Cell survival was analyzed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Whole-cell lysates were collected and immunoblotted with antibodies against Bcl-2, p-c-Jun, active caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), and apoptosis-inducing factor (AIF). The guinea pigs received intraperitoneal injections of cisplatin alone or following minocycline pretreatment. The auditory brainstem response was tested and the cochleae were harvested and evaluated using scanning electron microscopy. Results. Survival significantly increased in cells pretreated with minocycline compared with cells exposed to cisplatin alone. Cisplatin treatment increased the expression of active caspase 3, p-c Jun, PARP, and AIF, and pretreatment with minocycline attenuated this response. In animal study, the threshold shift by cisplatin injection in the auditory brainstem response was less pronounced in animals pretreated with minocycline. Scanning electron microscopy revealed more severe damage to the outer hair cells at the basal and middle turns than the apical turn. Conclusion. Minocycline partially protects against cisplatin-induced ototoxicity via both caspase-dependent and independent apoptosis pathways.
참고문헌 (20)
- Hamers FP, "Application of a neuroprotective ACTH(4-9) analog to affect cisplatin ototoxicity: an electrocochleographic study in guinea pigs", Eur Arch Otorhinolaryngol, 251(1), pp.23~29 (1994)
- Ravi R, "Mechanism of cisplatin ototoxicity: antioxidant system", Pharmacol Toxicol, 76(6), pp.386~394 (1995)
- Davis CA, "Manganese superoxide dismutase attenuates Cisplatin-induced renal injury: importance of superoxide", J Am Soc Nephrol, 12(12), pp.2683~2690 (2001)
- Boulikas T, "Cisplatin and platinum drugs at the molecular level: review", Oncol Rep, 10(6), pp.1663~1682 (2003)
- Domercq M, "Neuroprotection by tetracyclines", Trends Pharmacol Sci, 25(12), pp.609~612 (2004)
- Chen M, "Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease", Nat Med, 6(7), pp.797~801 (2000)
- Wang J, "Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria", J Biol Chem, 279(19), pp.19948~19954 (2004)
- Corbacella E, "Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures", Hear Res, 197(1), pp.11~18 (2004)
- Zong WX, "Alkylating DNA damage stimulates a regulated form of necrotic cell death", Genes Dev, 18(11), pp.1272~1282 (2004)
- Xu Y, "Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1", TRAF2-mediated JNK1 activation, 2006, pp.281(13), 8788~8795
- Yrjanheikki J, "Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia", Proc Natl Acad Sci U S A, 95(26), pp.15769~15774 (1998)
- Du Y, "Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease", Proc Natl Acad Sci U S A, 98(25), pp.14669~14674 (2001)
- Tikka T, "Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia", J Neurosci, 21(8), pp.2580~2588 (2001)
- Brundula V, "Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis", Brain, 125(6), pp.1297~1308 (2002)
- Zhu S, "Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice", Nature, 417(6884), pp.74~78 (2002)
- Wang X, "Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington’s disease", Proc Natl Acad Sci U S A, 100(18), pp.10483~10487 (2003)
- Alano CC, "Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations", Proc Natl Acad Sci U S A, 103(25), pp.9685~9690 (2006)
- Alano CC, "Players in the PARP-1 cell-death pathway: JNK1 joins the cast", Trends Biochem Sci, 31(6), pp.309~311 (2006)
- Cheng PW, "Correlation of increased activities of Na+, K+-ATPase and Ca2+-ATPase with the reversal of cisplatin ototoxicity induced by D-methionine in guinea pigs", Hear Res, 205(1), pp.102~109 (2005)
- Li G, "Cisplatin ototoxicity to the rat inner ear: a role for HMG1 and iNOS", Neurotoxicology, 27(1), pp.22~30 (2006)