Neuroscience Letters 441 (2008) 302–306 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Coffee improves auditory neuropathy in diabetic mice Bin Na Hong a , Tae Hoo Yi b , Raekil Park c , Sun Yeou Kim d , Tong Ho Kang e,∗ a Department of Audiology, Nambu University, Gwangju, South Korea b College of Life Sciences, Kyung Hee University, Gyeonggi, South Korea c Vestibulocochlear Research Center, Wonkwang University School of Medicine, Jeonbuk, South Korea d Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi, South Korea e Department of Oriental Pharmaceutical Development, Nambu University, 864-1, Wolgye-dong, Gwangsan-gu, Gwangju 506-706, South Korea article info Article history: Received 29 April 2008 Received in revised form 14 June 2008 Accepted 16 June 2008 Keywords: Coffee Trigonelline Caffeine Auditory neuropathy (AN) Diabetes Mouse abstract Coffee is a widely consumed beverage and has recently received considerable attention for its possible ben- eficial effects. Auditory neuropathy is a hearing disorder characterized by an abnormal auditory brainstem response. This study examined the auditory neuropathy induced by diabetes and investigated the action of coffee, trigonelline, and caffeine to determine whether they improved diabetic auditory neuropathy in mice. Auditory brainstem responses, auditory middle latency responses, and otoacoustic emissions were evaluated to assess auditory neuropathy. Coffee or trigonelline ameliorated the hearing threshold shift and delayed latency of the auditory evoked potential in diabetic neuropathy. These findings demonstrate that diabetes can produce a mouse model of auditory neuropathy and that coffee consumption potentially facilitates recovery from diabetes-induced auditory neuropathy. Furthermore, the active constituent in coffee may be trigonelline. © 2008 Elsevier Ireland Ltd. All rights reserved. Auditory neuropathy (AN) is a hearing disorder caused by dam- age to the eighth nerve, which is located between the inner ear (cochlea) and the brainstem. AN causes hearing impairment that is characterized by abnormal auditory nerve function in the presence of normal cochlear receptor activity and is reflected in preserved otoacoustic emissions (OAEs) [19]. The precise cause of AN is unknown, but researchers suspect that a number of factors may be contributory, including hyperbilirubinemia [8], infection [4], hypoxia [17], diabetic neuropathy [25], and genetic factors [24]. In patients with AN, sounds may be transmitted normally through the middle ear and the cochlea but are not transmitted normally from the cochlea or along the auditory nerve. AN with demyelination and axonal loss in the auditory nerve affects both the synchrony of firing and the capacity of nerve fibers to discharge at high rates [20]. When myelin degrades, the conduction of signals along the nerve can be delayed. In animal models and in patients with peripheral neuropathy, evoked potential latencies in electro- physiological tests in the nerve were found to increase [1]. In a previous report, delays in the latency of auditory evoked potentials were found in the STZ-induced diabetic mouse model [11]. ∗ Corresponding author. Tel.: +82 62 970 0163; fax: +82 303 0300 0030. E-mail address: panjae@gmail.com (T.H. Kang). Recently, investigations have revealed an improvement in hear- ing after steroid treatment in hearing-impaired subjects with AN [27] and have demonstrated effects of sodium thiosulfate, diethyldithiocarbamate, fosfomycin, and WR-2721 in ameliorating cisplatin-induced ototoxicity [7]. Coffee is one of the most commonly consumed beverages in the world. Although some people avoid drinking coffee because of the health risks it poses, several recent studies have shown that coffee consumption reduces the risks for developing Alzheimer’s disease [2], type 2 diabetes [5], and colon cancer [16]. To date, no research has examined the effects of coffee in preventing AN and in ameliorating hearing impairment. In the present study, the protective actions of coffee and one of its constituents, trigonelline, on the latencies and thresholds of auditory evoked potentials and otoacoustic emissions were evalu- ated in an AN mouse model created by streptozotocin induction. Coffee extract was prepared from Coffea arabica (Brazil), sup- plied by Dongsuh Co. Ltd. (Seoul, Korea). Roasted coffee beans (600 g) were extracted three times with distilled water for 2 h at 70 ◦ C. Following filtration, the solution was evaporated in vacuo. The dried coffee extract (88.0 g) was used as the coffee sample in the experiment. Trigonelline and caffeine in the coffee sample were analyzed by HPLC, performed as described by Casal et al. [6]. An analytical HPLC unit (Shimazu Co., Japan) and a reverse-phase Spherisorb ODS2 column (particle size, 5 m; 25.0 cm × 0.46 cm) were used. The solvent system was a gradient of 0.1M phos- 0304-3940/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2008.06.049