title: New Therapeutic Concept of NAD Redox Balance for Cisplatin Nephrotoxicity.
abstract: Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects such as ototoxicity, nephrotoxicity, and peripheral neuropathy. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses are closely associated with cisplatin-induced nephrotoxicity; however, the precise mechanism remains unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as a key regulator of cellular energy metabolism and homeostasis. Recent studies have demonstrated associations between disturbance in intracellular NAD(+) levels and clinical progression of various diseases through the production of reactive oxygen species and inflammation. Furthermore, we demonstrated that reduction of the intracellular NAD(+)/NADH ratio is critically involved in cisplatin-induced kidney damage through inflammation and oxidative stress and that increase of the cellular NAD(+)/NADH ratio suppresses cisplatin-induced kidney damage by modulation of potential damage mediators such as oxidative stress and inflammatory responses. In this review, we describe the role of NAD(+) metabolism in cisplatin-induced nephrotoxicity and discuss a potential strategy for the prevention or treatment of cisplatin-induced adverse effects with a particular focus on NAD(+)-dependent cellular pathways.
authors.affiliation: Center for Metabolic Function Regulation, Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Gi-Su
authors.initials: GS
authors.lastname: Oh
authors.affiliation: Center for Metabolic Function Regulation, Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Center for Metabolic Function Regulation, Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: AiHua
authors.initials: A
authors.lastname: Shen
authors.affiliation: Center for Metabolic Function Regulation, Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Su-Bin
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Sei-Hoon
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Hyeok
authors.initials: H
authors.lastname: Shim
authors.affiliation: Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.affiliation: Department of Oriental Medical Physiology, College of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Kang-Beom
authors.initials: KB
authors.lastname: Kwon
authors.affiliation: PAEAN Biotechnology, 160 Tachno-2 Street, Yuseong-gu, Daejeon 305-500, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kwak
authors.affiliation: Center for Metabolic Function Regulation, Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051437:Renal Insufficiency / Q000139:chemically induced / Q000473:pathology*
chemical_list: D017382:Reactive Oxygen Species; D009243:NAD; D002945:Cisplatin