Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 13, 4291-4303
eCollection

The Role of the Reactive Oxygen Species Scavenger Agent, Astaxanthin, in the Protection of Cisplatin-Treated Patients Against Hearing Loss

Affiliations
Review

The Role of the Reactive Oxygen Species Scavenger Agent, Astaxanthin, in the Protection of Cisplatin-Treated Patients Against Hearing Loss

Benyu Nan et al. Drug Des Devel Ther.

Abstract

Emerging evidence of significant hearing loss occurring shortly after cisplatin administration in cancer patients has stimulated research into the causes and treatment of this side effect. Although the aetiology of cisplatin-induced hearing loss (CIHL) remains unknown, an increasing body of research suggests that it is associated with excessive generation of intracellular reactive oxygen species (ROS) in the cochlea. Astaxanthin, a xanthophyll carotenoid, has powerful anti-oxidant, anti-inflammatory, and anti-apoptotic properties based on its unique cell membrane function, diverse biological activities, and ability to permeate the blood-brain barrier. In this review, we summarize the role of ROS in CIHL and the effect of astaxanthin on inhibiting ROS production. We focus on investigating the mechanism of action of astaxanthin in suppressing excessive production of ROS.

Keywords: astaxanthin; cisplatin; hearing loss; oxidative stress.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic of the proposed mechanism of cisplatin transportation and the generation of ROS in CIHL. Cisplatin is transported into cochlear cells by membrane transporters, including copper transporter 1 (CTR1), organic cation transporter 2 (OCT2), and mechanoelectrical transduction (MET), and is excluded by copper-extruding P-type ATPases (ATP7A and ATP7B), multidrug resistance protein 2 (MRP2), and volume-regulated anion channels (VRAC). Cisplatin induces ROS production in the inner ear via NADPH oxidase (NOX), xanthine oxidase (XO), cytochrome P450 (CYP450), induced nitric oxide synthase (iNOS), and disturbances in the mitochondrial electron transport chain. Abbreviations: IL, interleukin; STAT1, signal transducer and activator of transcription 1.
Figure 2
Figure 2
Chemical structure of astaxanthin (3,3ʹ-dihydroxy-β, β- carotene-4,4R′-dione).
Figure 3
Figure 3
Proposed mechanism by which astaxanthin inhibits ROS and apoptosis. Astaxanthin inhibits apoptosis and scavenges ROS, and modulates various intracellular pathways, predominantly MAPK, PI3K/Akt and Nrf2/ARE. It can also activate the specificity protein 1 (Sp1)–NMDA receptor subunit 1 (NR1) signalling pathway, which leads to cell death. Abbreviations: AST, astaxanthin; Akt, v-akt murine thymoma viral oncogene homologue; ARE, anti-oxidant response element; CREB, CAMP-responsive element binding protein; ERK, extracellular signal–regulated kinases; JNK, c-Jun N-terminal kinase; Keap1, cytosolic inhibitor of Nrf2; Nrf2, nuclear factor-erythroid 2-related factor 2; NF-κβ, nuclear factor-kappa B subunit; NQO1, NADH Quinone Dehydrogenase1; PTEN, phosphatase and tensin homolog.

Similar articles

See all similar articles

References

    1. Knight KRG, Kraemer DF, Neuwelt EA. Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol. 2005;23(34):8588–8596. doi:10.1200/Jco.2004.00.5355 - DOI - PubMed
    1. Sheth S, Mukherjea D, Rybak LP, Ramkumar V. Mechanisms of cisplatin-induced ototoxicity and otoprotection. Front Cell Neurosci. 2017;11:338. doi:10.3389/fncel.2017.00338 - DOI - PMC - PubMed
    1. Ambati RR, Phang SM, Ravi S, Aswathanarayana RG. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications–a review. Mar Drugs. 2014;12(1):128–152. doi:10.3390/md12010128 - DOI - PMC - PubMed
    1. Kuroki T, Ikeda S, Okada T, et al. Astaxanthin ameliorates heat stress-induced impairment of blastocyst development in vitro:–astaxanthin colocalization with and action on mitochondria. J Assist Reprod Genet. 2013;30(5):623–631. doi:10.1007/s10815-013-9987-z - DOI - PMC - PubMed
    1. Breglio AM, Rusheen AE, Shide ED, et al. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun. 2017;8(1):1654. doi:10.1038/s41467-017-01837-1 - DOI - PMC - PubMed

LinkOut - more resources

Feedback