HSP-70 as a nonspecific early marker in cisplatin ototoxicity

Ramírez‐Camacho, Rafael; Cítores, M.J.; Trinidad, Almudena; Verdaguer, José María; García-Berrocal, José Ramón; Marero, A. Martín; Puente, Á. Izquierdo De La; González-García, José Ángel; Vargas, Juan A.

doi:10.1080/00016480600951483

Cited by 11 publications

(14 citation statements)

References 12 publications

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“…Thus, activation and redistribution of bcl-2-like protein 4 (Bax) in the cytosol promote the release of cytochrome c from damaged mitochondria. Caspases 3 and 9 are activated by cytochrome c causing DNA damage mediated by activation of DNAase with loss of outer hair cells (OHC) and spiral ganglia.7 Furthermore, some studies showed that CDDP induced apoptosis in inner hair cells (IHC) in a caspase independent way too.8,9 Utricle hair cells, with a common embryological origin with cochlea hair cells, minimizes oxidative stress by endogenous mechanisms and protective molecules such as glutathione, heat proteins (HSPs), heme oxigenase and adenosine A1 receptors that are proved to reduce CDDP-induced apoptosis in vitro.10 HSP-70 is over expressed in CDDP treated animals over 14 days, 11 showing a correlation between its concentration and a decrease in caspase activity at the cochlea.12 Nevertheless, up-regulation of these protective molecules is not enough to settle CDDP-induced oxidative stress being necessary the systemic or local administration of protective drugs6 such as caspase inhibitors (caspase-3 inhibitor z-DEVD-fmk and caspase-9 inhibitor z-LEHD-fmk13, cannabinoid receptor 2 JWH-1514), antioxidants (Bucillamine15, caffeic acid,16 metformin17 Ginkgo biloba extract18) or corticoids (dexamethasone19, 6α-methylprednisolone20). The systemic administration of drugs is related to variable penetration into the inner ear due to the presence of a blood-cochlea barrier and undesired side effects.…”

Section: Introductionmentioning

confidence: 99%

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

Martín-Saldaña¹,

Palao-Suay

Trinidad³

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in: Nanomedicine: Nanotechnology, Biology and Medicine 12.4 (2016) Abstract 6α-Methylprednisolone-loaded surfactant-free nanoparticles have been developed to palliate cisplatin ototoxicity. Nanoparticles were based on two different amphiphilic pseudo-block copolymers obtained by free radical polymerization and based on N-vinyl pyrrolidone and a methacrylic derivative of α-tocopheryl succinate or α-tocopherol. Copolymers formed spherical nanoparticles by nanoprecipitation in aqueous media that were able to encapsulate 6α-methylprednisolone in their inner core. The obtained nanovehicles were tested in vitro using HEI-OC1 cells and in vivo in a murine model. Unloaded nanoparticles were not able to significantly reduce the cisplatin ototoxicity. Loaded nanoparticles reduced cisplatin-ototoxicity in vitro being more active those based on the methacrylic derivative of vitamin E, due to their higher encapsulation efficiency. This formulation was able to protect hair cells in the base of the cochlea, having a positive effect in the highest frequencies tested in a murine model. A good correlation between the in vitro and the in vivo experiments was found.Background Cisplatin (CDDP) is a highly effective chemotherapeutic agent against a variety of solid tumors including head and neck, lungs, ovary, bladder and testicles; however, it presents severe side-effects. Marullo et al1 described a double way of CDDP-induced cytotoxicity: CDDP binding to guanine bases on nuclear DNA and the formation of inter-and intra-strand chain crosslinking trigger cell apoptosis because of replication and transcription blockage; CDDP also has a direct effect on mitochondrial DNA resulting in the impairment of electron 32 transport chain protein synthesis leading to ROS generation. Increasing doses incorporated into protocols, with the aim of increasing cure rates, are related with serious adverse effects that affect kidney function, nervous system and hearing. CDDP induces apoptosis of inner ear cell by binding to DNA, reactive oxygen species (ROS) generation, increased lipid peroxidation and Ca 2+ influx, and inflammation events.2 Hearing impairment begins in the high frequencies and progresses to midrange when patient receives doses higher than 100 mg/m 2. Patients who receive ultrahigh doses of CDDP (150-225 mg/m 42 2), show hearing loss in the high and extended high frequencies in 100% of cases. 44 3 There is substantial variability in susceptibility to the ototoxic effects of CDDP. Rapid intravenous bolus injections, high cumulative doses, pre-existing hearing loss, renal insufficiency, anemia, hypoalbuminemia, and prior cranial irradiation are some of the factors that can play a role in CCDP toxicity. The incidence and severity of hearing loss

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Section: Introductionmentioning

confidence: 99%

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

Martín-Saldaña¹,

Palao-Suay

Trinidad³

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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“…However, other single-dose studies in rats and guinea pigs suggest that hearing loss has stabilized 5-7 days after the cisplatin injection [9,27].…”

Section: Discussionmentioning

confidence: 99%

Recovery of Hearing in Cisplatin-Induced Ototoxicity in the Guinea Pig with Intratympanic Dexamethasone

Çallı¹,

Pınar²,

Öncel³

et al. 2011

Indian J Otolaryngol Head Neck Surg

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The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection as a therapeutic agent against cisplatin-induced ototoxicity. Animals were randomly divided into three groups. Group one received intraperitoneal cisplatin alone, group two, received intratympanic dexamethasone after cisplatin ototoxicity had been demonstrated. Group three, which is control group, received intratympanic dexamethasone.Then we made three measurements. First we measured the baseline distortion product otoacustic emission (DPOAEs) of all the guine pigs. Second we injected cisplatin intraperitoneal group one and two the same day. Third we measured DPOAEs after 72 h of group one and two. Moreover DPOAEs were measured at the end of the first and second week only in group two. Cochleae were harvested and processed for electron microscopy after then. Values of The DPOAEs amplitudes and signal-to-noise ratio (SNR) at 1-6 kHz frequencies for group 1 after the injections significantly decreased over those before injections (P \ 0.05). In group 3, there were no significant differences in DPOAE amplitude and SNR values When they are compare before and after their intratympanic dexamethasone injections (P [ 0.05). In group 2, the DPOAEs measurements were close to significance at the end of the second week (P = 0.056). Intratympanic dexamethasone injection did not cause any ototoxic effect. Although intratympanic dexamethasone did not reach the statistically significant results, the measurements were close to significance. Intratympanic dexamethasone might have a significant therapeutic effect after cisplatin ototoxicity with different dose and application regimens.

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“…Hsp70 has been detected in the cochlea after acoustic injury [16] , gentamicin [17] and CDDP injections [18] and has shown a protective effect against cochlea damage. Recent research shows that Hsp70 is a nonspecific early marker in CDDP ototoxicity [19] .…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Geranylgeranylacetone on Cisplatin Ototoxicity

Yin

Xiu²,

Liu³

et al. 2008

Chemotherapy

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Background: Geranylgeranylacetone (GGA) has the ability to induce heat shock proteins and to protect cells from apoptotic insults. This study aims to investigate whether GGA has a protective effect on cisplatin (CDDP) ototoxicity. Methods: The auditory threshold was assessed using the auditory brainstem response test. Hsp70 and C-reactive protein expressions were investigated by Western blot analysis. The amount of hair cells was counted under scanning electron microscopy. Results: The auditory threshold and the percentage of missing outer hair cells in the CDDP group were significantly higher than in the GGA + CDDP group. C-reactive protein expression was less in the GGA + CDDP group compared with the CDDP group. Hsp70 expression showed an adverse result. Conclusion: It was suggested that GGA had a protective effect on CDDP ototoxicity.

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HSP-70 as a nonspecific early marker in cisplatin ototoxicity

Abstract: Western blot was positive in 77.8% of the animals in the 7 days group, decreasing to a 44.4% in the 90 days group. In the control group, Western blot was positive in 5.5%.

Cited by 11 publications

References 12 publications

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

Recovery of Hearing in Cisplatin-Induced Ototoxicity in the Guinea Pig with Intratympanic Dexamethasone

Protective Effect of Geranylgeranylacetone on Cisplatin Ototoxicity

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