Cisplatin effects on guinea pigs: cochlear histology and genotoxicity

Cacineli Marion De Franceschi,Tania Tochetto,Aron Ferreira Da Silveira,Mara Rejane Fantinel,Thaís Doeler Algarve

doi:10.1590/s1808-86942011000600009

Cacineli Marion De Franceschi, Tania Tochetto + Show 3 more

Open Access

https://doi.org/10.1590/s1808-86942011000600009

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Abstract

AbstractTo understand how the DNA answers to external agents such as cisplatin may be relevant to the diagnosis and treatment of hearing disorders caused by the administration of such drug. ObjectivesTo investigate the cisplatin influence on the cochlea and DNA of guinea pigs. Material and MethodsExperimental study carried out with 12 guinea pigs (Cavia porcellus). The inclusion criterion was the presence of Preyer's reflex and distortion-product otoacoustic emissions. Guinea pigs were divided into two groups: Control Group (CG) - made up of six guinea pigs, to which we administrated saline solution during six consecutive days, intraperitoneally; and a Study Group (SG) - made up of six guinea pigs, to which we administrated cisplatin during six consecutive doses of 3mg/kg/day intraperitoneally. Twenty-four hours after the last administration of cisplatin the guinea pigs were slaughtered, blood samples were collected and the cochleae were removed. ResultsThe administration of cisplatin did not cause identifiable changes to the DNA. Histological analysis showed changes in the organ of Corti and spiral ganglion. ConclusionCisplatin causes changes in cochlear histology, such as the loss of the normal microcytoarchitecture of the organ of Corti, and reduction of neurons of the spiral ganglion with cell alterations, however, DNA damage was not detected.

Highlights

Cisplatin is a broadly used chemotherapy agent in adults and children, to treat solid tumors, with excellent results; it has many side effects[1,2]
As it reaches the organ of Corti, cisplatin starts its deleterious actions with the support cells, followed by the outer hair cells, especially in the middle and basal turns, later the stria vascularis and auditory nerve[4]
The guinea pigs were assigned to two groups: Control Group (CG) – made up by six lab animals, to which a 0.9% saline solution was intraperitoneally injected during 6 consecutive days; Study Group (SG) – made up by six lab animals, to which six consecutive doses of 3mg/kg/day of cisplatin was intraperitoneally injected

Summary

Introduction

Cisplatin is a broadly used chemotherapy agent in adults and children, to treat solid tumors, with excellent results; it has many side effects[1,2]. Cisplatin toxicity is found in the kidneys, central and/ or peripheral nervous systems, bowels, bone marrow and the organ or Corti[3]. As it reaches the organ of Corti, cisplatin starts its deleterious actions with the support cells, followed by the outer hair cells, especially in the middle and basal turns, later the stria vascularis and auditory nerve[4]. During the administration of cisplatin, there is a block of the outer hair cells ionic channels, preventing stimulus transduction and causing hearing loss[5]. Cisplatin causes changes to the antioxidant system of the cochlea’s outer hair cells[3]. Oxidative stress happens when there is an increased production of free radicals or when antioxidant mechanisms are impaired[7]

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