Recombinant human erythropoietin prevents ischemia-induced apoptosis and necrosis in explant cultures of the rat organ of Corti.
This study was designed to evaluate the effect of recombinant human erythropoietin (rhEPO), insulin-like growth factor-1 (rhIGF-1) and epidermal growth factor (rhEGF) on ischemia-induced hair cell loss in an organotypic cochlea culture. The apical, middle and basal parts of the organs of Corti (newborn rat, postnatal days 3-5) were exposed to ischemia (3.5 h) in glucose-free artificial perilymph (pO2 10-20 mmHg) with or without growth factors. Controls were exposed to normoxia. Twenty-four hours after the onset of ischemia, the cultures were stained using tetramethyl rhodamine isothiocyanate (TRITC) phalloidin (hair cells), propidium iodide (membrane integrity) and apoptosis detection kit (DNA-fragmentation). Ischemia (3.5 h) induced a hair cell loss of 20 and 40% in the middle and basal cochlear parts, respectively, and an increase of the numbers of PI-stained and DNA-fragmented nuclei (controls 0-1, ischemia 4-7 nuclei/100 microm). The basal part was more affected than the apical one. rhEPO and rhIGF-1 significantly attenuated the ischemia-induced hair cell loss by reducing processes involved in apoptosis and necrosis. rhEPO has been in clinical use for more than a decade and found to be well tolerated. Therefore, rhEPO could be an effective drug for the prevention of hearing loss via a hair cell protective mechanism.
Andreeva
Nadezhda
N
Brain Research Institute, Academy of Medical Sciences, Odukha 5, 105064 Moscow, Russia.
Nyamaa
Amarjargal
A
Haupt
Heidemarie
H
Gross
Johann
J
Mazurek
Birgit
B
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000235:genetics / Q000494:pharmacology*; D004921:Erythropoietin / Q000235:genetics / Q000494:pharmacology*; D006198:Hair Cells, Auditory / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology*; D007511:Ischemia / Q000150:complications / Q000473:pathology*; D009336:Necrosis / Q000473:pathology / Q000517:prevention & control; D009925:Organ of Corti / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage
D011994:Recombinant Proteins; D004921:Erythropoietin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I