Age Affects the Mitigating Efficacy of Riboflavin Against Cisplatin-Induced Toxicity In Vivo

Abstract

Cis-diamminedichloroplatinum (CP), a prominent anticancer drug, exerts toxic insults that are functional to various factors that compromise its antineoplastic activity. Riboflavin (RF) is an essential vitamin and photosensitizer that ameliorates CP-induced toxic insults in vivo in a dose-dependent manner. The aim of the present study is to investigate how age can influence the ameliorative effect of RF against CP-induced toxicity. Ninety male mice were divided into three age groups: young, adult, and old for the present investigation under an established treatment strategy with CP, RF, and their combinations under photoillumination for 1 mo. Their kidneys and serum samples were assessed for redox status [superoxide dismutase, catalase, reduced glutathione, malondialdehyde (MDA), carbonyl contents, and glutathione-S-transferase], biochemical analysis (renal function markers-nitric oxide), comet assay, and histopathology. The adult group showed not only the strongest resistance against the CP-induced toxicity but also the better ameliorative effect of RF followed by the young and old groups, respectively, with well-maintained redox status concomitant with the level of renal function markers, MDA, and carbonyl contents near the control values. Furthermore, comet assay and histopathological evaluation confirmed the results in a dose-dependent manner. Hence, age is an important patient-related factor that can influence the final clinical outcome under personalized chemoradiotherapy.