In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity

Abstract

Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in: Experimental and Toxicologic Pathology 68.4 (2016): 197-204 A B S T R A C TIntroduction: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases.Aim: To evaluate the protective effects of lutein on HEI-OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity.Materials and Methods: In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5-100 mM) and to 25 mM cisplatin for 24 h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n = 8) received intratympanic lutein (0.03 mL) (1 mg/mL) in the right ear and saline solution in the left one to determine the toxicity of lutein. Group B (n = 8) received also intraperitoneal cisplatin (10 mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n = 12) received intratympanic lutein (0.03 mL) (1 mg/mL) to quantify lutein in cochlear fluids (30 min,1 h and 5 days after treatment). Hearing function was evaluated by means of Auditory Steady-State Responses before the procedure and 5 days after (groups A and B). Morphological changes were studied by confocal laser scanning microscopy.Results: In vitro study: Lutein significantly reduced the cisplatin-induced cytotoxicity in the HEI-OC1 cells when they were pre-treated with lutein concentrations of 60 and 80 mM. In vivo study: Intratympaniclutein (1 mg/mL) application showed no ototoxic effects. However it did not achieve protective effect against cisplatin-induced ototoxicity in Wistar rats.Conclusions: Although lutein has shown beneficial effects in other pathologies, the present study only obtained protection against cisplatin ototoxicity in culture cells, but not in the in vivo model. The large molecule size, the low dose administered, and restriction to diffusion in the inner ear could account for this negative result

Ototoxicity and Platinum Uptake Following Cyclic Administration of Platinum-Based Chemotherapeutic Agents

“…A variety of antioxidants have been shown to reduce cisplatin-induced ototoxicity in animal models (Rybak et al 1999 ; Lopez-Gonzalez et al 2000 ; Choe et al 2004 ). Studies that show antioxidants protects against hair cell death in vitro (Kim et al 2014 ; Astolfi et al 2008 , Roldán-Fidalgo et al 2016 , reviewed in Sheth et al 2017 ) suggest that antioxidant-mediated protection can function downstream of cisplatin entry into the inner ear, since in vitro preparations eliminate the blood-labyrinth barrier and allow cisplatin to directly access hair cells. However, to date no studies have shown that antioxidants reduce cisplatin-induced hearing loss in humans.…”

Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use

“…The cell lines and the cochlear explants indicated low toxicity for paromomycin, similar to that of apramycin, while the in-vivo studies demonstrated that it was clearly ototoxic, and comparable to neomycin and GM. Divergent data from in-vitro and in-vivo ototoxicity models have been recorded previously 53,54 . These might be related to the presence of vulnerable cell types in-vivo that have a role in the overall response to treatment and that are not present in in-vitro models, or to differential differentiation stages and signalling pathways being activated in the in-vitro versus in-vivo models 25,55–57 .…”

The Effect of Different Routes of Injection of Bone Marrow Mesenchymal Stem Cells on Parotid Glands of Rats Receiving Cisplatin: A Comparative Study

“…Twenty rats received single intraperitoneal injection of Cisplatin drug (Hospira, UK Limited, Warwickshire) (10 mg/kg) each ( 17 ) and considered as positive control.…”