Browsing by Author "Pelit, A"

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    The effect of resveratrol on the histologic characteristics of the cochlea in diabetic rats
    Erkan, SO; Tuhanioglu, B; Gürgen, SG; Özdas, T; Tastekin, B; Pelit, A; Görgülü, O
    Objectives/Hypothesis The aim of this study was to investigate changes in the cochlea and the potential dose-dependent effects of resveratrol (RSV) against diabetes mellitus (DM) ototoxicity. Study Design Animal model. Methods Twenty-four male Wistar albino rats were divided into four groups. Baseline distortion product otoacoustic emission (DPOAE) measurements were evaluated. Group I was the control group, group II was made diabetic with single-dose streptozotocin, and groups III and IV were rendered diabetic as group II and administered 10 and 20 mg RSV, respectively, intraperitoneally for 4 weeks. All animals were sacrificed after repeated DPOAE measurement. Apoptosis was investigated using caspase-3, Bax (Bcl-associated X protein), and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining. Results The DPOAE values in the diabetic group were found to be significantly lower compared with the other groups at 5,714 Hz and 8,000 Hz (P < .05). No significant difference in otoacoustic emission was detected in the comparison of the RSV doses (P > .05). The histopathologic investigation using caspase-3, Bax, and TUNEL staining showed that the mean rank of the diabetic group was significantly higher compared with the RSV10, RSV20, and control groups (DM > RSV10 > RSV20 > control) (P < .05). Conclusions These results imply that RSV administration offered statistically significant protection for the cochleas of rats against diabetes. This protective effect improved histologically with higher doses.
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    Pterostilbene protects cochlea from ototoxicity in streptozotocin-induced diabetic rats by inhibiting apoptosis
    Özdas, S; Tastekin, B; Gurgen, SG; Özdas, T; Pelit, A; Erkan, SO; Tuhanioglu, B; Gülnar, B; Görgülü, O
    Diabetes mellitus (DM) causes ototoxicity by inducing oxidative stress, microangiopathy, and apoptosis in the cochlear sensory hair cells. The natural anti-oxidant pterostilbene (PTS) (trans-3,5-dimethoxy-4-hydroxystylbene) has been reported to relieve oxidative stress and apoptosis in DM, but its role in diabetic-induced ototoxicity is unclear. This study aimed to investigate the effects of dose-dependent PTS on the cochlear cells of streptozotocin (STZ)-induced diabetic rats. The study included 30 albino male Wistar rats that were randomized into five groups: non-diabetic control (Control), diabetic control (DM), and diabetic rats treated with intraperitoneal PTS at 10, 20, or 40 mg/kg/day during the four-week experimental period (DM + PTS10, DM + PTS20, and DM + PTS40). Distortion product otoacoustic emission (DPOAE) tests were performed at the beginning and end of the study. At the end of the experimental period, apoptosis in the rat cochlea was investigated using caspase-8, cytochrome-c, and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL). Quantitative real-time polymerase chain reaction was used to assess the mRNA expression levels of the following genes:CASP-3, BCL-associated X protein (BAX), andBCL-2. Body weight, blood glucose, serum insulin, and malondialdehyde (MDA) levels in the rat groups were evaluated. The mean DPOAE amplitude in the DM group was significantly lower than the means of the other groups (0.9-8 kHz; P < 0.001 for all). A dose-dependent increase of the mean DPOAE amplitudes was observed with PTS treatment (P < 0.05 for all). The Caspase-8 and Cytochrome-c protein expressions and the number of TUNEL-positive cells in the hair cells of the Corti organs of the DM rat group were significantly higher than those of the PTS treatment and control groups (DM > DM + PTS10 > DM + PTS20 > DM + PTS40 > Control; P < 0.05 for all). PTS treatment also reduced cell apoptosis in a dose-dependent manner by increasing the mRNA expression of the anti-apoptosisBCL2gene and by decreasing the mRNA expressions of both the pro-apoptosisBAXgene and its effectorCASP-3and the ratio ofBAX/BCL-2in a dose-dependent manner (P < 0.05 compared to DM for all). PTS treatment significantly improved the metabolic parameters of the diabetic rats, such as body weight, blood glucose, serum insulin, and MDA levels, consistent with our other findings (P < 0.05 compared to DM for all). PTS decreased the cochlear damage caused by diabetes, as confirmed by DPOAE, biochemical, histopathological, immunohistochemical, and molecular findings. This study reports the first in vivo findings to suggest that PTS may be a protective therapeutic agent against diabetes-induced ototoxicity.