Pharmacological activation of NQO1 increases NAD⁺ levels and attenuates cisplatin-mediated acute kidney injury in mice.

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 neuropathy. Various mechanisms, such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses, are critically involved in cisplatin-induced adverse effects. As NAD(+) is a cofactor for various enzymes associated with cellular homeostasis, we studied the effects of increased NAD(+) levels by means of

Nad(p)h

quinone oxidoreductase 1 (NQO1) activation using a known pharmacological activator (β-lapachone) in wild-type and NQO1(-/-) mice on cisplatin-induced renal dysfunction in vivo. The intracellular NAD(+)/NADH ratio i

SUBMITTER: Oh GS 

PROVIDER: S-EPMC3944666 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature