Darbepoetin Alpha Ameliorates Neuronal Damage in a Rat Model of Acute Ethanol Intoxication

Seymen, Pınar; Aytaç, Erman; Esen, Fehim; Tel, Çiğdem; Demir, Fatih; Genc, Habibe; Uzun, Hafize; Öz, Büğe; Altuğ, Tuncay; Seymen, Hakki Oktay

doi:10.3109/00207454.2012.738732

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…Further studies have revealed that acute alcohol intoxication may be involved in alcoholic psychosis and alcoholic encephalopathy, suggesting that it may cause irreversible damage to central nervous system [6,7]. Recently, pathophysiology and etiology of acute alcohol intoxication through experimental practice on rodent models have gotten much attention, among which rat models have been universally adopted to discover the influence of acute alcohol intoxication on the central nervous system (CNS) [8,9]. Abundant rat models of acute alcohol intoxication have shown that acute alcohol intoxication may stimulate genetic expression of neural cells of the cerebellum, which may take significant part in the prognosis and treatment of CNS lesions [10,11].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication

Kong

Yang

et al. 2014

Mol Biol Rep

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This study aimed to identify gene expression profile in the rat brain resulting from acute alcohol intoxication (AAI). Eighteen SD rats were divided into the alcohol-treated group (n = 9) and saline control group (n = 9). Periorbital blood samples were taken to determine their blood alcohol content by gas chromatography. Tissue sections were analyzed by H and E staining and biochemical assays. Real-time reverse transcription PCR was used to validate microarray data. Statistical analysis was carried out using SPSS18.0 software (Version 18.0, SPSS Inc., Chicago, IL, USA). H and E staining demonstrated that alcohol-treated rats showed no obvious pathological changes in nerve cells compared with those in the control group. Biochemical tests revealed that alcohol-treated rats had lower superoxide dismutase activity than those in the control group (167.3 ± 10.3 U/mg vs. 189.2 ± 5.9 U/mg, P < 0.05). Furthermore, the malondialdehyde levels in alcohol-treated rats were higher than those in the control group (3.48 ± 0.24 mmol/mg vs. 2.51 ± 0.23 mmol/mg, P < 0.05). Microarray data presented 366 up-regulated genes and 300 down-regulated genes in the AAI rat brain. Gene ontology analysis identified 31 genes up-regulated and 39 down-regulated among all differentially expressed genes. Twenty-four pathways showed significant differences, including 12 pathways involved with up-regulated genes and 12 pathways involved with down-regulated genes. Selected genes showed significantly different expression in both alcohol-treated and control groups (P < 0.05). Gene expression analysis enabled clustering of alcohol intoxication-related genes by function. These genes expression may be potential targets for treatment or drug screening for acute alcohol intoxication.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication

Kong

Yang

et al. 2014

Mol Biol Rep

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“…A review reported that erythropoiesis-stimulating agents have neurodevelopmental improvement effects in preterm and term infants (22). In addition, it has been reported to be protective against ethanol intoxicationinduced neurotoxicity and CDDP nephrotoxicity (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

Protective Role of Darbepoetin in Cisplatin-Induced Ototoxicity

BAYRAK

OLGUN

ESKİCİOĞLU

et al. 2023

Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi

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Amaç: Darbepoetin-alfa (DPO) uygulamasının sisplatine bağlı ototoksik etkiyi önleyici rolü olup olmadığının in-vivo olarak değerlendirilmesi amaçlandı. Materyal metod: Çalışmada 28 adet wistar albino rat kullanılarak 4 grup oluşturuldu. Grup 1 (intraperitoneal) IP salin verilen kontrol grubu, Grup 2 sisplatin (16mg/kg IP tek doz), Grup 3 DPO (25 μg/kg IP), Grup 4 sisplatin verilmeden 24 saat önce ve verildikten yarım saat sonra 25 μg/kg tek doz IP DPO uygulanan grup. Ratlara ajan uygulamalarından önce ve deneyin 7. gününde distorsiyon ürünü otoakustik emisyon (DPOAE) ve işitsel uyarılmış beyin sapı potansiyelleri (ABR) yapıldı. İşitme ölçümleri sonrasında ratlar sakrifiye edildi. Apoptotik hücre ölümü kulak dokusunda kaspaz-3, -8, -9 ve Nrf2 ve Hem oksijenaz-1 (HO-1), NQQ1, Glutatyon (GST) gibi Nrf2 ilişkili antioksidan ve iNOS, nNOS ekspresyon düzeyleri immünohistokimyasal yöntemle çalışıldı. Serum glutatyon (GSH) ve anti-inflamatuar TNF-α ve IL-1 protein düzeyleri ELISA kitleri kullanılarak belirlendi. Bulgular: Sisplatin uygulaması ile işitme ölçümlerinde kontrole göre ototoksik etkileri gösteren tüm frekanslarda işitme kaybı saptandı. İmmunohistokimyasal doku düzeyinde gerçekleştirilen incelemelerde sisplatin uygulanan grupta iç kulakta strüktürel değişiklikler, beyin ve sinir dokularında nekroz ve nekroptoz saptandı. Darbepoetinin sisplatinin ortaya çıkardığı iç kulak ve beyin hasarlarını önleyici etkileri hem apoptotik protein ekspresyonları hem de oksidatif stres ile ilişkili belirteçler olan Nrf-2 ve ilişkili HO-1, NQO1, iNOS ve nNOS, GST ve anti-inflamatuar proteinleri üzerinden saptandı. Sonuç: Bu çalışmada sisplatinin oluşturduğu ototoksisitede DPO’in koruyucu etkileri apoptozun azaltılması, antioksidan Nrf-2 ve hedef proteinler ve glutatyon düzeylerinin artışı yanında anti-inflamatuar proteinler üzerinden geliştiği gösterilmiştir.

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“…Daberpoetin-alpha, an EPO derivative with 3 times the circulation half-life of endogenous EPO, due to having more sialic acid moieties, is not only beneficial for treating anemia, but also has a neuroprotective activity similar to that of EPO in stroke, intracerebral hemorrhage, and acute ethanol intoxication models (Seymen et al, 2013; Belayev et al, 2005; Grasso et al, 2009). On the other hand, the hematopoietic activity of EPO and its derivatives sometimes causes polycythemia and thrombosis, making them inappropriate for clinical use to treat CNS disorders.…”

Section: Cns Protection By Epo Treatmentmentioning

confidence: 99%

Enhancement of ventricular-subventricular zone-derived neurogenesis and oligodendrogenesis by erythropoietin and its derivatives

Kaneko

Kako

Sawamoto

2013

Front. Cell. Neurosci.

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In the postnatal mammalian brain, stem cells in the ventricular-subventricular zone (V-SVZ) continuously generate neuronal and glial cells throughout life. Genetic labeling of cells of specific lineages have demonstrated that the V-SVZ is an important source of the neuroblasts and/or oligodendrocyte progenitor cells (OPCs) that migrate toward injured brain areas in response to several types of insult, including ischemia and demyelinating diseases. However, this spontaneous regeneration is insufficient for complete structural and functional restoration of the injured brain, so interventions to enhance these processes are sought for clinical applications. Erythropoietin (EPO), a clinically applied erythropoietic factor, is reported to have cytoprotective effects in various kinds of insult in the central nervous system. Moreover, recent studies suggest that EPO promotes the V-SVZ-derived neurogenesis and oligodendrogenesis. EPO increases the proliferation of progenitors in the V-SVZ and/or the migration and differentiation of their progenies in and around injured areas, depending on the dosage, timing, and duration of treatment, as well as the type of animal model used. On the other hand, EPO has undesirable side effects, including thrombotic complications. We recently demonstrated that a 2-week treatment with the EPO derivative asialo-EPO promotes the differentiation of V-SVZ-derived OPCs into myelin-forming mature oligodendrocytes in the injured white matter of neonatal mice without causing erythropoiesis. Here we present an overview of the multifaceted effects of EPO and its derivatives in the V-SVZ and discuss the possible applications of these molecules in regenerative medicine.

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Darbepoetin Alpha Ameliorates Neuronal Damage in a Rat Model of Acute Ethanol Intoxication

Abstract: Our findings suggest that darbepoetin alpha has neuroprotective effect in acute ethanol intoxication, possibly through its antioxidant effect.

Cited by 5 publications

References 15 publications

RETRACTED ARTICLE: Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication

RETRACTED ARTICLE: Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication

Protective Role of Darbepoetin in Cisplatin-Induced Ototoxicity

Enhancement of ventricular-subventricular zone-derived neurogenesis and oligodendrogenesis by erythropoietin and its derivatives

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