Histopathologic results of long-term sildenafil administration on rat inner ear.
OBJECTIVE
Sildenafil, a selective inhibitor of phosphodiesterase type 5, is widely used for the treatment of erectile dysfunction. Although cochlear effects of phosphodiesterase type 5 inhibitors remain still unclear because of inadequate data, some evidence that recently emerged indicates that these medications may be responsible for hearing impairment. In the present study, we aimed to examine the histopathologic effects of long-term sildenafil use on the cochlea in a rat model.


METHODS
The study was performed with adult male Wistar albino rats. The control group was fed on standard laboratory diet. The study group was applied orally with sildenafil therapy, 1.5 mg/kg once a day for 45 days. Rats were anesthetized and decapitated. Each temporal bone was dissected, and the cochleas were removed en bloc. The inner-ear biopsy specimens were examined histologically with hematoxylin and eosin and caspase 3 immunoreaction under light microscopy.


RESULTS
Hematoxylin and eosin staining showed no distinctive difference between the control group and the sildenafil group. With immunohistochemical examination, caspase 3 immunoreactivity was observed in the sildenafil group. In the control group, caspase 3 immunoreactivity was not observed.


CONCLUSIONS
The caspase 3 immunoreactivity in the sildenafil group was strongly associated with an increase in apoptotic events in the cochlea. Long-term use of sildenafil can cause hearing impairment through increased apoptosis.
Department of ENT and Head and Neck Surgery, Dicle University Medical College, Diyarbakir, Turkey. drsalihbakir@gmail.com
Salih
S
Bakir
Uğur
U
Firat
Ramazan
R
Gün
Yaşar
Y
Bozkurt
Ediz
E
Yorgancilar
Vefa
V
Kiniş
Necmettin
N
Penbegül
Osman
O
Gökalp
Ismail
I
Topçu
D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007758:Ear, Inner; D005500:Follow-Up Studies; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors
D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D053148:Caspase 3