PENTİLENTETRAZOL-İNDÜKLÜ NÖBETLERDE ERİTROPOİETİN ÖN TEDAVİSİNİN KARACİĞER, BÖBREK, KALP DOKUSU ÜZERİNE ETKİLERİ; OKSIDATİF MARKIRLAR, PROLİDAZ VE SİALİK ASİT AÇISINDAN DEĞERLENDİRME

Abstract

Amaç: Antiepileptik ajan olarak sıklıkla çalışılan eritropoietinin (EPO)’nun periferik dokular üzerindeki etkileri araştırılmamıştır. Bu çalışmada pentilentetrazol (PTZ) ile indüklenen nöbetlerde EPO ön tedavisinin kalp, böbrek ve karaciğer dokularında malondialdehit (MDA), ileri protein oksidasyon ürünleri (AOPP), superoksid dismutaz (SOD), prolidaz ve sialik asit (SA) seviyelerine etkisi araştırıldı. Gereç ve Yöntem: Otuz üç erişkin erkek sıçan üç gruba ayrıldı. Salin enjekte edilmiş kontrol grubu, nöbetleri indüklemek için 60 mg/kg PTZ enjekte edilmiş grup, nöbetlerden 24 saat önce 3000 IU/kg EPO enjekte edilmiş grup. Nöbet şiddeti ve nöbet gecikmesi puanlandıktan sonra, sıçanlar sakrifiye edildi, dokular biyokimyasal analizler için hemen çıkarıldı. Bulgular: Pentilentetrazol ile indüklenen nöbetler, böbrekte MDA (p<0,01) ve karaciğerde AOPP’yi arttırdı (p<0,05), ancak kalp dokusunda bu markırları değiştirmedi. Her üç dokuda da SOD nöbetler nedeniyle değişmedi. Kalpte SA arttı (p<0,001), böbrekte azaldı (p<0,001), karaciğerde değişmedi. Prolidaz sadece böbrekte arttı (p<0,05), diğer dokularda değişmedi. EPO ön tedavisi nöbet şiddetini azalttı ve nöbet latansını artırdı. EPO böbrekte MDA artışını engelledi (p<0,01), ancak AOPP’yi artırdı (p<0,05) ve SOD’u azalttı (p<0,01) ve prolidazı nöbetlerin arttırdığından daha fazla artırdı (p<0,01). EPO ön tedavisi, karaciğerde AOPP artışını önledi (p<0,05), ancak kalp ve böbrekte PTZ’nin neden olduğu SA değişikliklerinde etkisizdi. Sonuç: Nöbetlerde kalp dokusundaki SA artışının nöbet-ilişkili kardiak aritmiler bağlamında araştırmayı hak eden orijinal bulgu olduğunu düşünüyoruz. Ayrıca EPO ön tedavisinin nöbet engelleyici etkisine rağmen özellikle böbrek dokusunda artmış protein oksidasyonu ve prolidaz da ileri araştırmayı gerektiren diğer önemli bulgudur.

Keywords

• Eritropoietin
• PTZ-indüklü nöbetler
• oksidatif stres belirteçleri
• sialik asit
• prolidaz
• periferik dokular

EFFECTS OF ERYTHROPOIETIN PRETREATMENT ON LIVER, KIDNEY, HEART TISSUE IN PENTYLENTETRAZOL-INDUCED SEIZURES; EVALUATION IN TERMS OF OXIDATIVE MARKERS, PROLIDASE AND SIALIC ACID

Abstract

Objective: The effects of erythropoietin (EPO) which has been frequently studied as an anti-epileptic agent, on peripheral tissues have not been investigated. This study investigated the effects on malondialdehyde (MDA), advanced protein oxidation products (AOPP), superoxide dismutase (SOD), prolidase and sialic acid (SA) levels in the heart, kidney and liver tissues of EPO pretreatment in pentylenetetrazole (PTZ)-induced seizures. Material and Method: Thirty three male adult rats were divided into three groups. A saline-injected control group, a 60 mg/kg PTZ-injected group to induce seizures and a 3000 IU/kg EPO-injected group 24 hours before seizures. After seizure severity and seizure latency were scored, the rats sacrificed, the tissues were immediately removed for biochemical analyses. Results: The PTZ-induced seizures increased MDA in kidney (p<0.01) and AOPP in liver (p<0.05) but didn’t alter these markers in heart tissue. In all three tissues, SOD didn’t change due to seizures. The SA levels increased in the heart (p<0.001), decreased in the kidney (p<0.001), and were unchanged in liver. Prolidase increased (p<0.05) only in kidney, and was unchanged in other tissues. EPO-pretreatment decreased seizure severity and increased seizure latency. It prevented the increase in MDA in the kidney (p<0.01) but increased AOPP (p<0.05) and decreased SOD (p<0.01) and further increased prolidase more than the seizures increased (p<0.01). EPO-pretreatment prevented the increase in AOPP in the liver (p<0.05) but was ineffective in PTZ-induced SA changes in the heart and kidney. Conclusion: We think that the increase in the heart SA level in seizures is an original finding and deserves investigation in the context of seizure-related cardiac arrhytmias. Also, despite the EPO’s anti-seizure effect, increased protein oxidaiton and prolidase, especially in the kidney, is an other important finding that needs further research.

Keywords

• Erythropoietin
• PTZ-induced seizures
• oxidative stress markers
• sialic acid
• prolidase
• peripheral tissues

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