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Halotan İle Oluşan Karaciğer Toksisitesinin Belirlenmesinde Paraoksonazın (PON 1) Yeri

Determination of Paraoxonase Activity in Halothane Induced Hepatotoxicity

Journal Name:

  • Fırat Tıp Dergisi

Publication Year:

  • 2004

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Objective: %20 of halothane is metabolized in endoplasmic reticulum of hepatocyte by oxidation and reduction. Paraoxonase is a natural antioxidative enzyme either found in plasma and not in liver as a high level. The aim of the study is expressing of biochemical and histopathologic relation between effects of paraoxonase which synthesized and released by liver and halothane on liver. Materials and Methods: In this study, 70 rats which ranged between 180-200 gr used. 10 of them divided as control group. In the study % 1.5 halothane applied for 2 hours in first (60 rats), third (40 rats) and fifth (20 rats) day. 10 rats sacrified before and after for each application than blood and liver sampling performed. Paraoxonase, and malonil dialdehide levels measured in this blood samples. This blood samples are also examined as histopathologically. Results and Conclusions: Significant and opposite relation were found between paraoxonase levels (169.63 ± 49.07), histopathologic damage, MDA (0.583±0.059) and other enzyme levels (p<0.05) in the studay groups. While histopathologic damage increases with repetative application, paraoxonase (110.71±9.70) level decreases. In the later period paraoxonase level (192.12±70.12) will increase and degree of damage will decrease (p<0.05). Conclusions: The indicator of suppression of protein synthesis by halothane in liver is that decreasing of paraoxonase synthesis while application. In the later period histopathologic results will show opposite relation with this enhancement. In the literature there is no relationship between halothane and paraoxonase because of this new studies are needed for expression of pathologic changes. ©2004, Fırat Üniversitesi, Tıp Fakültesi
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Abstract (Original Language): 
Amaç: Halotanın %20'si oksidatif ve redüktif yolla karaciğerde endoplazmik retikulumda metabolize edilir. Hepatositlerdeki lipid peroksidasyonu sonucu oluşan reaktif metabolitler doku hasarına neden olurken, karaciğerdeki proteinlerin sentezi de halotan tarafından baskılanır. Rat karaciğeri ve plazmasında yüksek oranda bulunan paraoksonaz (PON1), doğal antioksidan bir enzimdir. Sentez ve salınımı karaciğer tarafından yapılan PONl'in aktivitesi ile halotanın tekrarlanan uygulamalarında karaciğere etkisi arasındaki ilişkinin biyokimyasal ve histopatolojik varlığı amaçlanmıştır. Gereç ve Yöntem: Çalışmada 180-200 gr ağırlığındaki 70 rat çalışmaya alındı. Ratlardan 10 tanesi kontrol grubunda yer aldı. Çalışmada 1. gün (60 rat), 3. gün (40 rat) ve 5. gün (20 rat) %1.5 oranında halotan 2 saat süreyle uygulandı. Her uygulama öncesinde 10 ve sonrasında 10 rat sakrifeye edilip, kan ve karaciğerleri alındı. Kalan 10 rat 12. günde sakrifiye edilerek kan ve karaciğerleri alındı. Alınan kan örneklerinde PON1 ve malonil dialdehit (MDA) düzeyleri ölçüldü. Karaciğer örnekleri histopatolojik olarak incelendi. Malonil dialdehit ve PON 1 enzim düzeyleri ile hasar değerlendirmeleri eş zamanlı yapılıp bulgular istatistiksel olarak değerlendirildi. Bulgular ve Sonuç: Çalışma grubunda PON1 düzeyi (169.63±49.07) ile histopatolojik hasar, MDA (0.583±0.059) arasında anlamlı ters bir ilişki bulundu (p<0.05). Tekrarlanan uygulamalarda histopatolojik hasar artarken PON1 (110.71±9.70) düşmekte (p<0.05), geç dönemde PON1(192.12±70.12) artarken hasar derecesi azalmaktadır (p<0.05). Karaciğerde halotan tarafından baskılanan protein yapımının göstergesi olarak PON1 sentezi de uygulama sırasında düşmektedir. Geç dönemde PON1 düzeyi artarken histopatolojik bulgular buna ters ilişkili uyum göstermektedir. PON1'ın karaciğer mikrozomlarında antioksidan sistemde özellikli rol oynadığı görülmektedir. Halotan ve PON1 ilişkisine literatürde rastlanılmamış olması nedeniyle patofizyolojik değişmelerin açıklığa kavuşturulması için başka çalışmalara gereksinim vardır. ©2004, Fırat Üniversitesi, Tıp Fakültesi
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  • 4
103-107
  • Turkish

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