Pterostilbene protects cochlea from ototoxicity in streptozotocin-induced diabetic rats by inhibiting apoptosis
Autor: | Talih Özdaş, Seren Gülşen Gürgen, Birgül Gülnar, Aykut Pelit, Sanem Okşan Erkan, Birgül Tuhanioğlu, Bora Taştekin, Orhan Görgülü, Sibel Özdaş |
---|---|
Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Physiology medicine.medical_treatment Apoptosis medicine.disease_cause Biochemistry Antioxidants chemistry.chemical_compound Endocrinology Medical Conditions 0302 clinical medicine Animal Cells Stilbenes Medicine and Health Sciences Insulin bcl-2-Associated X Protein Neurons Staining Multidisciplinary Cell Death Caspase 3 Cell Staining Malondialdehyde Blood Sugar Cochlea Body Fluids Blood Cell Processes 030220 oncology & carcinogenesis Inner Ear Outer Hair Cells Medicine Anatomy Cellular Types Research Article medicine.drug medicine.medical_specialty Endocrine Disorders Science Blood sugar Research and Analysis Methods Protective Agents Streptozocin Diabetes Mellitus Experimental 03 medical and health sciences Ototoxicity Internal medicine Diabetes mellitus Diabetes Mellitus otorhinolaryngologic diseases medicine Animals Rats Wistar Diabetic Endocrinology Dose-Response Relationship Drug business.industry Body Weight Biology and Life Sciences Afferent Neurons Cell Biology Acoustics medicine.disease Streptozotocin Hormones 030104 developmental biology Gene Expression Regulation chemistry Ears Specimen Preparation and Treatment Metabolic Disorders Cellular Neuroscience business Head Oxidative stress Neuroscience |
Zdroj: | PLoS ONE, Vol 15, Iss 7, p e0228429 (2020) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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), and BCL-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-apoptosis BCL2 gene and by decreasing the mRNA expressions of both the pro-apoptosis BAX gene and its effector CASP-3 and the ratio of BAX/BCL-2 in 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. |
Databáze: | OpenAIRE |
Externí odkaz: |