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
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