Trimethyltin-induced cochlear degeneration in rat

Abstract

Trimethyltin (TMT) is an occupational and environmental health hazard behaving as a potent neurotoxin known to affect the central nervous system as well as the peripheral auditory system. However, the mechanisms underlying TMT-induced ototoxicity are poorly understood. To elucidate the effects of TMT on the cochlea, a single injection of 4 or 8 mg/kg TMT was administered intraperitoneally to adult rats. The compound action potential (CAP) threshold was used to assess the functional status of the cochlea and histological techniques were used to assess the condition of the hair cells and auditory nerve fibers. TMT at 4 mg/kg produced a temporary CAP threshold elevation of 25–60 dB that recovered by 28 d post-treatment. Although there was no hair cell loss with the 4 mg/kg dose, there was a noticeable loss of auditory nerve fibers particularly beneath the inner hair cells. TMT at 8 mg/kg produced a large permanent CAP threshold shift that was greatest at the high frequencies. The CAP threshold shift was associated with the loss of outer hair cells and inner hair cells in the basal, high-frequency region of the cochlea, considerable loss of auditory nerve fibers and a significant loss of spiral ganglion neurons in the basal turn. Spiral ganglion neurons showed evidence of soma shrinkage and nuclear condensation and fragmentation, morphological features of apoptotic cell death. TMT-induced damage was greatest in the high-frequency, basal region of the cochlea and the nerve fibers beneath the inner hair cells were the most vulnerable structures.

Use of Radical Oxygen Species Scavenger Nitrones to Treat Oxidative Stress-Mediated Hearing Loss: State of the Art and Challenges

“…Sensorineural hearing loss (SNHL) is the most common sensory deficit in adults, and is associated with normal aging. SNHL is intensified due to the exposure to pollutants such as carbon monoxide (CO) ( Marcano Acuña et al, 2019 ), hydrogen cyanide ( Fechter et al, 2002 ), trimethyltin ( Yu et al, 2016 ) and acrylonitrile, as well as by the combination of high levels of noise and these toxins ( Fechter et al, 2004 ; Pouyatos et al, 2009 ). SNHL is also caused by drugs such as aminoglycosides and cisplatin ( Kros and Steyger, 2019 ; Murillo-Cuesta et al, 2021 ).…”