Cisplatin-induced Ototoxicity In Rats Research Articles

The role of apoptosis in cisplatin-induced ototoxicity in rats

isplatina e um agente quimioterapico frequentemente usado para o tratamento de varias linhagens de neoplasias. A ototoxicidade e um dos efeitos colaterais causadores de significativa morbidade e que limita sua utilizacao. Este estudo teve por objetivo avaliar o papel da apoptose na ototoxicidade por cisplatina.

The role of apoptosis in cisplatin-induced ototoxicity in rats

SummaryCisplatin is a chemotherapy agent frequently used to treat different types of neoplasia. Ototoxicity is one of the side-effects which cause significant morbidity and limits its use. This study aimed at assessing the role of apoptosis in cisplatin-induced ototoxicity.Designexperimental study.Materials and Methodsmale Wistar rats were treated with intraperitoneal cisplatin, in the doses of 24 and 16 mg/kg. The animals were assessed by means of distortion product evoked otoacoustic emissions (DPEOAE) or brainstem evoked auditory potentials (BEAP) in the third (D3) and fourth (D4) days after drug infusion onset. Following that, their cochleas were removed for immunohistochemical studies of apoptosis - TUNEL method.Resultsthe group treated with 24 mg/kg showed a significant reduction in DPEOAE amplitude, and such fact was not seen with the 16 mg/kg. Both doses caused an increase in BEAP electrophysiological threshold in D3 and D4. Apoptosis was the injury mechanism responsible for the cisplatin-induced ototoxicity −16 mg/kg dose, when the animals were assessed on D3.Conclusionapoptosis may be involved in the cisplatin-induced ototoxicity, depending on the dose and time of injury assessment.

Distortion-product otoacoustic emissions and auditory brainstem responses sensitivity assessment in cisplatin-induced ototoxicity in rats

Cisplatin (cis-diamminedicloroplatinum) is an antineoplastic drug used in the treatment of a variety of cancers, especially head-and-neck cancer. Its ototoxi...

Distortion-product otoacoustic emissions and auditory brainstem responses sensitivity assessment in cisplatin-induced ototoxicity in rats

SummaryCisplatin (cis-diamminedicloroplatinum) is an antineoplastic drug used in the treatment of a variety of cancers, especially head-and-neck cancer. Its ototoxicity, however, has been noted as a common side-effect which limits its use and causes significant morbidity.Aimto assess distortion-product otoacoustic emissions (DPOAE) and brainstem evoked response audiometry (BERA) sensitivity to detect secondary ototoxicity caused by different doses and means of administration of cisplatin in rats.Study DesignExperimental.Materials and MethodsMale Wistar rats were intraperitoneally (i.p.) injected with 24 mg/kg cisplatin, divided into three equal doses (8mg/kg) or a single i.p. injection of 16 mg/kg. The animals were evaluated by distortion product otoacoustic emission (DPOAE) or brainstem evoked response audiometry (BERA) on the 3rd and 4th days after the cisplatin injection.ResultsTreatment with cisplatin 24 mg/kg resulted in significant DPOAE decrease and it raised the BERA electrophysiological threshold. The 16mg/kg dose could not significantly reduce the DPOAE amplitude, but it raised the animals' hearing thresholds – detected by the BERA.ConclusionIn rats, BERA was more sensitivity than DPOAE at detecting cisplatin-induced ototoxicity in rats considering different doses and means of administration.

Light microscopy study of cisplatin-induced ototoxicity in rats

Although most studies on animal ototoxicity employ scanning electron microscopy, all cochlear structures may be identified with light microscopy. This paper describes a simple method of histological assessment of cisplatin-induced ototoxicity in rats, and relates morphological changes to functional changes in hearing detected by distortion product evoked otoacoustic emissions. Male Wistar rats were injected with 8 mg/kg/day cisplatin, or with an equivalent volume of saline solution, for three consecutive days. They underwent distortion product evoked otoacoustic emission testing at baseline and at 24 or 48 hours after the last administration. At the end of the experiment, the animals were sacrificed and their cochleae were retrieved and prepared for haematoxylin and eosin staining. A four-point scoring system was used to grade injury to the external ciliated cells, as indicated by the number of cells absent from the basal turn of the cochlear duct. A four-point scoring system was also used to grade stria vascularis injury, as indicated by the degree of shrinkage of the intermediate cells. Scores were significantly higher in groups treated with cisplatin compared with controls. Morphological changes were confirmed by decreased distortion product evoked otoacoustic emission amplitudes in animals treated with cisplatin. This method is simple to perform with routine histology equipment and is appropriate for the study of acute, cisplatin-induced ototoxicity in rats.

Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: antioxidant defense system.

This study investigated the alterations that occur in auditory brainstem-evoked responses (ABRs) concurrent with changes in cochlear concentrations of glutathione (GSH), lipid peroxidation, and antioxidant enzyme activity in cisplatin-induced ototoxicity and in dose-dependent otoprotection by an antioxidant lipoate. Male Wistar rats were divided into different groups and were treated as follows, with: (1) vehicle (saline) control; (2) cisplatin (16 mg/kg, i.p.); (3) lipoate (100 mg/kg, i.p.) plus saline; (4) cisplatin plus lipoate (25 mg/kg); (5) cisplatin plus lipoate (50 mg/kg), and (6) cisplatin plus lipoate (100 mg/kg). Post-treatment ABRs were evaluated after three days, the rats were sacrificed, and cochleae were harvested and analyzed. The cisplatin-injected rats showed ABR threshold elevations above the pre-treatment thresholds. Rats treated with lipoate plus cisplatin did not show significant elevation of hearing thresholds. Cisplatin administration resulted in a depletion of cochlear GSH concentration (69% of control), whereas, cisplatin-plus-lipoate treatment increased GSH concentration close to control value. Cisplatin-treated rats showed a decrease in cochlear superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities (57, 78, 59, and 58% of control, respectively), and an increase in malondialdehyde (MDA) concentration (196% of control). Cochlear SOD, CAT, GSH-Px, and GR activities and MDA concentrations were restored in the rats injected with cisplatin plus graded doses of lipoate than those with cisplatin alone. It is concluded that cisplatin-induced ototoxicity is related to impairment of the cochlear antioxidant defense system, and the dose-dependent otoprotection conferred by an antioxidant lipoate against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant defense system.

Protective Effect of Fosfomycin against Cisplatin-induced Ototoxicity in Rats

Protective Effect of Fosfomycin against Cisplatin-induced Ototoxicity in Rats