Protective effect of pentoxifylline on amikacin-induced ototoxicity in rats ☆,☆☆,★ Güler Berkiten, MD a , Ziya Salturk, MD b, ⁎ , İlhan Topaloğlu, MD a , Hilmi Uğraş a a Okmeydanı Training and Research Hospital Şişli, İstanbul Turkey b Suluova State Hospital, Suluova, Amasya Turkey Received 29 January 2012 Abstract Purpose: This experimental study was performed to investigate the possible protective effect of pentoxifylline (PTX) on amikacin-induced ototoxicity in rats. Materials and methods: In this study, 21 healthy female rats were randomly assigned to 1 of 3 groups: the amikacin group (n = 8), the amikacin + PTX group (n = 8), and the control group (n = 5). The amikacin group received amikacin (200 mg·kg - 1 ·day - 1 ) intramuscularly once daily for 14 days. The amikacin + PTX group received intramuscular injections of amikacin (200 mg·kg - 1 ·day - 1 ) once daily for 14 days and PTX (25 mg·kg - 1 ·day - 1 ) once daily via gastric gavage for 14 days. The control group received saline solution (1 mL·day - 1 intraperitoneal injections) once daily for 14 days. The hearing levels of the rats were evaluated using distortion product otoacoustic emissions before and after treatment. Results: The distortion product otoacoustic emissions' amplitude levels (decibel, sound pressure levels) measured before and after treatment at frequencies of 4000, 6000, and 8000 Hz revealed that values of the amikacin group dropped significantly at the end of treatment (P b .01). In contrast, the amikacin + PTX and the control groups showed no significant difference at the end of the treatment compared with the initial measurements (P N .05). Conclusion: The results showed that PTX has protective effects on hearing functions in amikacin- induced ototoxicity in rats. © 2012 Elsevier Inc. All rights reserved. 1. Introduction Aminoglycosides are effective antibiotics with a wide spectrum [1,2] that have long been used for the treatment of infections. Despite their effectiveness, aminoglycosides are associated with side effects including ototoxicity, nephro- toxicity, and vestibulotoxicity [1,3,4]. Amikacin, a semisynthetic first derivative of aminogly- cosides [4], is made from the natural drug kanamycin A by acylation. Because of its structure, it is resistant to bacterial enzymes that can inactivate natural aminoglyco- sides such as tobramycin, kanamycin, and gentamicin [1,2]. Amikacin causes the formation of free oxygen radicals leading to apoptosis. This mechanism causes ototoxicity and deafness [5]. Pentoxifylline (PTX), a methylxanthine derivative and phosphodiesterase inhibitor with hemorrheologic properties, affects arachidonic acid metabolism and inhibits proin- flammatory mediators such as tumor necrosis factor α (TNF-α). The TNF-α has a role in the activation of macrophages and increasing the proinflammatory secretion of neutrophils, resulting in the stimulation of apoptosis. These effects trigger cell death, resulting in necrosis of Available online at www.sciencedirect.com American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 689 – 692 www.elsevier.com/locate/amjoto ☆ This study was presented at the Turkish National Congress in Antalya, Turkey on October 2010. ☆☆ No financial support was provided in any stage of the study or preparation of the manuscript. ★ There is no conflict of interest between authors. ⁎ Corresponding author. Suluova State Hospital, Suluova, Amasya Turkey. E-mail address: ziyasalturk@gmail.com (Z. Salturk). 0196-0709/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjoto.2012.05.007