title: D‑galactose‑induced mitochondrial DNA oxidative damage in the auditory cortex of rats.
abstract: Chronic administration of D‑galactose (D‑gal) is a useful method for establishing a model of natural aging in the auditory system. Previous studies have demonstrated that NADPH oxidases (NOXs) may be an important source of reactive oxygen species (ROS) in the peripheral auditory system (PAS) and cause an increase in mitochondrial DNA (mtDNA) common deletion (CD) levels in the PAS and central auditory system (CAS) of rats with D‑gal‑induced aging. However, the source of the ROS in the CAS and the mechanisms of age‑related hearing loss (ARHL) have yet to be elucidated. In the present study, male Sprague Dawley rats were administered a daily injection of D‑gal (150, 300 and 500 mg/kg, respectively) for eight weeks. All three doses of D‑gal caused a significant increase in the expression of NOX2, 8‑hydroxy‑2‑deoxyguanosine, a biomarker of DNA oxidative damage, and uncoupling protein 2, together with a decrease in the mitochondrial total antioxidant capabilities in the auditory cortex, as compared with the control rats (injected daily with the same volume of 0.9% saline for eight weeks). The levels of the mtDNA CD were also increased in the auditory cortex of the D‑gal‑induced aging rats. These findings suggest that both NOX‑ and mitochondria‑associated ROS generation may contribute to mtDNA oxidative damage in the auditory cortex of the CAS of D‑gal‑induced aging rats. This study may provide novel insight into the development of ARHL.
authors.affiliation: Department of Otorhinolaryngology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China.
authors.forename: Zhengde
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Otorhinolaryngology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: College of Pharmacy, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, P.R. China.
authors.forename: Shixiong
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Gao
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001303:Auditory Cortex / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000235:genetics; D003849:Deoxyguanosine / Q000235:genetics; D005690:Galactose / Q000494:pharmacology*; D007473:Ion Channels / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000235:genetics; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D007473:Ion Channels; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D003849:Deoxyguanosine; D005690:Galactose