Kim Hyung-Jin, Oh Gi-Su, Shen AiHua, Lee Su-Bin, Khadka Dipendra, Pandit Arpana, Shim Hyeok, Yang Sei-Hoon, Cho Eun-Young, Song Jeho, Kwak Tae Hwan, Choe Seong-Kyu, Park Raekil, So Hong-Seob
Center for Metabolic Function Regulation & Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea.
Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea.
Hear Res. 2015 Aug;326:30-9. doi: 10.1016/j.heares.2015.04.002. Epub 2015 Apr 17.
Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced ototoxicity. Although much attention has been directed at identifying ways to protect the inner ear from cisplatin-induced damage, the precise underlying mechanisms have not yet been elucidated. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as an important regulator of cellular energy metabolism and homeostasis. NAD(+) acts as a cofactor for various enzymes including sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs), and therefore, maintaining adequate NAD(+) levels has therapeutic benefits because of its effect on NAD(+)-dependent enzymes. Recent studies demonstrated that disturbance in intracellular NAD(+) levels is critically involved in cisplatin-induced cochlear damage associated with oxidative stress, DNA damage, and inflammatory responses. In this review, we describe the importance of NAD(+) in cisplatin-induced ototoxicity and discuss potential strategies for the prevention or treatment of cisplatin-induced ototoxicity with a particular focus on NAD(+)-dependent cellular pathways.
耳毒性是接受顺铂化疗患者的一个重要问题。众多研究表明，包括氧化应激、DNA损伤和炎症反应在内的多种机制与顺铂诱导的耳毒性密切相关。尽管人们已将大量注意力集中在寻找保护内耳免受顺铂诱导损伤的方法上，但确切的潜在机制尚未阐明。辅助因子烟酰胺腺嘌呤二核苷酸（NAD(+)）已成为细胞能量代谢和体内平衡的重要调节因子。NAD(+)作为包括沉默调节蛋白（SIRTs）和聚（ADP-核糖）聚合酶（PARPs）在内的多种酶的辅助因子，因此，维持足够的NAD(+)水平具有治疗益处，因为它对依赖NAD(+)的酶有影响。最近的研究表明，细胞内NAD(+)水平的紊乱与顺铂诱导的与氧化应激、DNA损伤和炎症反应相关的耳蜗损伤密切相关。在本综述中，我们描述了NAD(+)在顺铂诱导的耳毒性中的重要性，并讨论了预防或治疗顺铂诱导的耳毒性的潜在策略，特别关注依赖NAD(+)的细胞途径。
