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Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment withbucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.
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참고문헌 (26)
참고문헌 신청
Babu E / 1999 / Rehabilitating role of glutathione ester on cisplatin induced nephrotoxicity / Ren fail 21 : 209 ~ 217
Clerici WJ / 1995 / Direct effects of reactive oxygen species on cochlear outer hair cell shape in vitro / Hear Res 84 : 30 ~ 40
Fausti SA / 1993 / High-frequency monitoring for early detection of cisplatin ototoxicity / Arch Otolaryngol Head Neck Surg 119 : 661 ~ 666
Freeman BA / 1982 / Biology of disease : free radicals and tissue injury / Lab Invest 47 : 412 ~ 426
Goldstein JC / 2000 / The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant / Nat Cell Biol 2 : 156 ~ 162
Clerici WJ / 1995 / Direct effects of reactive oxygen species on cochlear outer hair cell shape in vitro / Hear Res 84 : 30 ~ 40
Fausti SA / 1993 / High-frequency monitoring for early detection of cisplatin ototoxicity / Arch Otolaryngol Head Neck Surg 119 : 661 ~ 666
Freeman BA / 1982 / Biology of disease : free radicals and tissue injury / Lab Invest 47 : 412 ~ 426
Goldstein JC / 2000 / The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant / Nat Cell Biol 2 : 156 ~ 162
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