Otoprotective effect of recombinant erythropoietin in a model of newborn hypoxic-ischemic encephalopathy

Olgun, Yüksel; Kırkım, Günay; Kolatan, Efsun; Kıray, Müge; Bağrıyanık, Hüsnü Alper; Serbetcioglu, Bulent; Yılmaz, Osman; Gökmen, Ali Necati; Ellıdokuz, Hülya; Kumral, Abdullah; Sütay, Semih

doi:10.1016/j.ijporl.2013.01.029

Cited by 10 publications

(10 citation statements)

References 21 publications

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“…In addition to its erythropoietic effects, EPO has been found to be cytoprotective in various models of cellular injury by its antiapoptotic effects. Olgun et al [25] reported that rhEPO decreased hypoxic-ischemic encephalopathy-induced apoptotic cell death in the cochlea, spiral ganglion, and central auditory pathways of newborn rats and prevented hypoxic-ischemic encephalopathy-induced hearing loss. Rjiba-Touati et al [26] demonstrated that treatment with EPO decreased CDDP-induced apoptotic cell death and tubular injury in rat kidney.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of Recombinant Human Erythropoietin against Cisplatin-Induced Ototoxicity

Doğan¹,

Olgun²,

Kırkım³

et al. 2015

Int Adv Otol

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OBJECTIVE:To investigate the potential protective effect of recombinant human erythropoietin (rhEPO) against cisplatin-induced ototoxicity. MATERIALS and METHODS:Twenty-eight Wistar albino rats were divided randomly into four groups, and baseline distortion product otoacoustic emission (DPOAE) responses and auditory brainstem response (ABR) thresholds were obtained. Group I received intraperitoneal (i.p.) saline, Group II received a single dose of i.p. 2000 IU/kg rhEPO, and Group III and Group IV received a single dose of i.p. 16 mg/kg cisplatin injection. In Group IV, 2000 IU/kg rhEPO was also injected intraperitoneally two times: 24 hours before and 30 minutes after i.p. 16 mg/kg cisplatin injection. DPOAEs and ABR measurements were repeated 72 hours following cisplatin administration, and the animals were sacrificed. The cochleae of animals were evaluated histopathologically by light microscopy, and percentage of apoptotic cells in the spiral ganglion was then determined by immunofluorescence analysis. RESULTS:Post-treatment auditory assessment revealed significant ABR threshold elevations at click and 6 kHz and 8 kHz frequencies in Group III compared to Groups I and II (p<0.05). In Group III, 8 kHz DPOAEs were also significantly deteriorated compared to Groups I and II (p<0.05). In Group IV, the ABR thresholds and DPOAEs were protected at click and 6 kHz; there was no statistically significant difference between Group IV and Group I at those frequencies. Concomitant administration of rhEPO and cisplatin significantly reduced apoptosis and cell damage. The apoptotic cell percentage of spiral ganglions in Group IV was significantly less than in Group III (p=0.01). CONCLUSION:Our results showed that i.p. application of rhEPO inhibited apoptosis and prevented cisplatin-induced ototoxicity in rats.

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Section: Discussionmentioning

confidence: 99%

The Protective Effect of Recombinant Human Erythropoietin against Cisplatin-Induced Ototoxicity

Doğan¹,

Olgun²,

Kırkım³

et al. 2015

Int Adv Otol

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“…Many studies have demonstrated Epo's antiapoptotic effects. 50,53,[58][59][60][61][62][63][64][65][66][67][68][69] Additionally, Epo has also been shown to have anti-inflammatory, neurotrophic, and antioxidant properties, along with having a role in promoting angiogenesis, neurogenesis, and oligodendrogenesis. 47,[70][71][72][73][74][75][76][77][78][79][80] Epo may protect the brain from edema by upregulation of aquaporin channels.…”

Section: Figurementioning

confidence: 99%

The potential of erythropoietin to treat asphyxia in newborns

Pet¹,

Juul

2014

RRN

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Perinatal asphyxia is a cause of significant neonatal morbidity worldwide. Lack of oxygenation and perfusion to the neonatal brain leads to energy failure and cell death. Currently, therapeutic hypothermia is the standard of care for term infants with hypoxicischemic encephalopathy, but as it has shown only modest effects on survival and morbidity, additional neuroprotective agents are needed. Erythropoietin has been extensively studied as a neuroprotective agent for infants who suffer a hypoxic-ischemic brain injury. It has multiple mechanisms of action, in both preventing cell death and promoting tissue repair. Studies have progressed over time from in vitro to in vivo studies, first in animals and now in humans, with several Phase I/II trials completed and Phase III trials underway. As therapeutic hypothermia has become the standard of care in treating term infants with hypoxic-ischemic encephalopathy, studies must now evaluate other neuroprotective agents, including erythropoietin, used in concert with therapeutic hypothermia. Erythropoietin has shown promise as a neuroprotective agent in animal and human models, both alone and together with hypothermia.

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“…and E.K.) 20 For ultrastructural investigations, temporal bones was carefully harvested; after soft tissue was removed cochleas were opened laterally and samples were treated according to the previously discussed technique. 20…”

Section: Histopathological Proceduresmentioning

confidence: 99%