<i>D</i>-Methionine Attenuates Inner Hair Cell Loss in Carboplatin-Treated Chinchillas

Abstract

Carboplatin, a second-generation platinum-based antineoplastic drug, preferentially destroys inner hair cells (IHCs) in the chinchilla while sparing outer hair cells (OHCs). D-Methionine (D-Met), a sulfur-containing amino acid, has been shown to protect hair cells from cisplatin damage in rats, but its ability to protect IHCs from carboplatin damage has not yet been evaluated in the chinchilla. We tested whether D-Met would protect the hair cells in the chinchilla from carboplatin. Animals were divided into two groups: a control group that only received carboplatin (100 mg/kg, i.p.) and an experimental group that received 300 mg/kg D-Met (i.p.) 30 min before carboplatin treatment. Ototoxicity was assessed by measuring the amount of IHC and OHC loss. Average IHC loss in the group treated with D-Met was 62% compared with 84% in the untreated control group. Thus, D-Met causes a statistically significant reduction in IHC loss induced by carboplatin.

Damage and threshold shift resulting from cochlear exposure to Paraquat-generated superoxide

“…Pretreatment with antioxidants has also been shown limit cochlear damage and hearing loss from cisplatin exposure 0378 (Campbell et al, 1996;Kopke et al, 1997). Similar observations have been made with carboplatin, regarding increases in ROS after administration (Husain et al, 2001) and protection with antioxidant pretreatment (Lockwood et al, 2000). Additionally, Clerici and Yang (1996) were the first to show that generators of superoxide, hydrogen peroxide, and the hydroxyl radical induced significant shifts in the compound action potential threshold when introduced into the perilymph (Clerici and Yang, 1996).…”

Prevention of noise- and drug-induced hearing loss with d-methionine

“…Specifically, D-met reduces cisplatin-induced strial edema, protects the optical density ratios between the marginal cells and intermediate cells reflecting preservation of the marginal cell cytoplasmic organelles, and prevents bulging and compression of the marginal cells' luminal edges. For systemically administered carboplatin, injected D-met protects against the carboplatin-induced selective inner hair cell loss that occurs in the chinchilla (Lockwood et al, 2000).…”

“…In pigmented guinea pigs, D-met protects against cisplatin-induced (Wimmer et al, 2004) and gentamicin-induced ototoxicity (Sha and Schacht, 2000). In the chinchilla, D-met protects against topical cisplatin-induced ototoxicity (Korver et al, 2002), systemic carboplatin-induced ototoxicity (Lockwood et al, 2000) and noise-induced hearing loss Kopke et al, 2002). For in vitro studies, D-met protects against; cisplatin-induced outer hair cell loss, and in conjunction with brain derived neurotrophic factor, protects against both cisplatin-induced spiral ganglion cell and outer hair cell loss in organ of Corti explants harvested from 3 or 4 day post-partum Wistar rats Gabaizadeh et al, 1997).…”

Ototoxic Hearing Loss and Retinoblastoma Patients

“…Another otoprotectant against carboplatin ototoxicity that has been evaluated in animal models is D-Methionine (D-Met). Lockwood et al (2000) found that carboplatin-induced cell loss was reduced in chinchillas treated with D-met compared to untreated controls.…”