Brodifacoum’un sıçan karaciğeri üzerine etkileri


Tezin Yürütüldüğü Kurum: Ankara Üniversitesi, Fen Bilimleri Enstitüsü, Türkiye

Tezin Onay Tarihi: 2012

Tezin Dili: Türkçe

Öğrenci: Ceren GENİŞ

Danışman: NURSEL GÜL

Özet:

Bu çalışmada Wistar sıçanların karaciğeri üzerine brodifacoum’un sitolojik etkileri ışık ve elektron mikroskobunda araştırıldı. Hayvanlar, kontrol grubu, 24 saat, 4 gün ve 7 gün brodifacoum uygulamalı dört gruba ayrıldı (n=5 her grupta). Dimetil sülfoksitle hazırlanan brodifacoum gastrik gavaj ile oral yoldan tek doz (0,2 mg/kg)olarak verildi. Karaciğer örnekleri 24 saat, 4 gün ve 7 gün sonra sıçanlardan alındı. Dokular tespit edildi, dehidre edildi, propilen oksite yerleştirildi ve Araldite CY212 gömme ortamına alındı. Dokuların ultramikrotomla yarı ince ve ince kesitleri alındı.Işık mikroskobu incelemelerinde kontrol grubu sıçan karaciğerlerinin normal hücrelere ve sinüzoid yapısına sahip olduğu gözlendi. 24 saatlik brodifacoum uygulanmış sıçanlarla kontrol grubu sıçanların karaciğerlerinin benzer özellik gösterdiği tespit edildi. Zaman artışına bağlı olarak ( 4. günden 7. güne) brodifacoum uygulanmış sıçanların karaciğerindeki hepatositlerin sitoplazmalarında materyal kaybı, lipit damlacıkları ve yoğun madde birikiminin olduğu tespit edildi.Elektron mikroskobu incelemelerinde 24 saatlik brodifacoum uygulanmış sıçanların karaciğerlerinde ışık mikroskobunun aksine bazı değişiklikler tespit edildi. Hepatositlerin sitoplazmasında vakuoller, kristaları erimiş mitokondriler ve çekirdeklerinde kromatin yığınları tespit edildi. Aynı zamanda sinüzoidlerde sitoplazmik materyali azalmış eritrositler gözlendi. Dört günlük brodifacoum uygulanan sıçanların karaciğerlerinde çekirdek invaginasyonu, nukleusta kromatin materyalinin çevreye yerleşmesi, mitokondriyal kristaların erimesi ve lizozomal yapılar gibi birçok ince yapısal değişiklikler meydana geldi. Diğer sıçan gruplarına göre yedi günlük brodifacoum uygulanmış sıçanların karaciğerinde ağır hasarlı yapısal değişiklikler tespit edildi; karaciğer hepatositlerinde çok sayıda vakuol ve lipit damlacıkları, kristaları erimiş mitokondriler, sisternaları genişlemiş granüllü endoplazmik retikulum keseleri gibi bozukluklar gözlendi. Ayrıca hepatositlerin çekirdeklerinde kromatin yığınlaşması, morfolojik invaginasyonlar gibi çekirdek anormallikleri tespit edildi. Bunun yanı sıra hemolize olmuş eritrositler, lipit damlacıkları ve madde birikimi bu grubun karaciğer sinüzoidlerinde gözlendi. Sunulan bu çalışma brodifacoum’un sıçanların karaciğerlerinde hücresel anormalliklere sebep olduğunu gösterdi.AbstractIn this study, cytological effects of brodifacoum on the liver of Wistar rats were investigated by light and transmission electron microscopy. Animals were divided into four groups (n=5 in each group): Control group, 24 hours Brodifacoum-treated group, 4 days Brodifacoum-treated group, and 7 days brodifacoum-treated group. Brodifacoum prepared in dimethyl sulphoxide was orally administered to rats as a single dose (0.2 mg/kg) by gasrtric gavage. After 24 hours, 4 days and 7 days liver tissues were obtained from sacrified rats. The tissues were fixed, dehidrated, placed into propylene oxide and embedded in araldite CY212. Semi-thin sections and thin sections of tissues were cut by ultramicrotome.In light microscopic observations, it was determined that control groups have normal cells and normal sinuzoid structure. After 24 hours the liver of brodifacoum-treated rats have similar properties with liver of control group rats. Accumulation of condensed matter and lipid droplets, loss cytoplasmic material cytoplasms of hepatocytes were determined in brodifacoum-treated rat liver depending on the increase in time (from 4 days to 7 days).In contrast light microscopic observations, there are several ultrastructural changes were determined in 24th hours brodifacoum-treated liver cells in electron microscobic observations. Hepatocytes had vacuoles, mitochondria with melting cristae in their cytoplasms and clumping chromatin material in their nuclei. Also, the sinuzoids of 24th hours brodifacoum-treated livers had contained erythrocytes with loss cytoplasmic material. Severe structural changes were observed in liver tissues 4th days brodifacoum-treated group than that of control group. There were several ultrastructural changes of hepatocytes in 4th days brodifacoum-treated rats liver such as invaginations and periferal localization of chromatin material in nuclei, mitochondrial cristae melting and lysosomal structures etc. Heavy damages ultrastructural changes were determined in 7th days brodifacoum-treated rats liver than the other groups rats. It was observed that the liver hepatocytes had dissorder organells which are rough endoplasmic reticulum with dilated cisternae, mitochondria with melting cristae, numerous lipid droplets and vacuoles. Also, nucleus abnormalities were determined such as morphological invaginations and chromatin clumping in hepatocytes nuclei. In additionally, hemolyzed erythrocytes, large number of lipid droplets and material deposition in sinuzoids in the liver this group were seen.Presented study showed that the brodifacoum causes cellular abnormalities of rat liverIn this study, cytological effects of brodifacoum on the liver of Wistar rats were investigated by light and transmission electron microscopy. Animals were divided into four groups (n=5 in each group): Control group, 24 hours Brodifacoum-treated group, 4 days Brodifacoum-treated group, and 7 days brodifacoum-treated group. Brodifacoum prepared in dimethyl sulphoxide was orally administered to rats as a single dose (0.2 mg/kg) by gasrtric gavage. After 24 hours, 4 days and 7 days liver tissues were obtained from sacrified rats. The tissues were fixed, dehidrated, placed into propylene oxide and embedded in araldite CY212. Semi-thin sections and thin sections of tissues were cut by ultramicrotome. In light microscopic observations, it was determined that control groups have normal cells and normal sinuzoid structure. After 24 hours the liver of brodifacoum-treated rats have similar properties with liver of control group rats. Accumulation of condensed matter and lipid droplets, loss cytoplasmic material cytoplasms of hepatocytes were determined in brodifacoum-treated rat liver depending on the increase in time (from 4 days to 7 days).In contrast light microscopic observations, there are several ultrastructural changes were determined in 24th hours brodifacoum-treated liver cells in electron microscobic observations. Hepatocytes had vacuoles, mitochondria with melting cristae in their cytoplasms and clumping chromatin material in their nuclei. Also, the sinuzoids of 24th hours brodifacoum-treated livers had contained erythrocytes with loss cytoplasmic material. Severe structural changes were observed in liver tissues 4th days brodifacoum-treated group than that of control group. There were several ultrastructural changes of hepatocytes in 4th days brodifacoum-treated rats liver such as invaginations and periferal localization of chromatin material in nuclei, mitochondrial cristae melting and lysosomal structures etc. Heavy damages ultrastructural changes were determined in 7th days brodifacoum-treated rats liver than the other groups rats. It was observed that the liver hepatocytes had dissorder organells which are rough endoplasmic reticulum with dilated cisternae, mitochondria with melting cristae, numerous lipid droplets and vacuoles. Also, nucleus abnormalities were determined such as morphological invaginations and chromatin clumping in hepatocytes nuclei. In additionally, hemolyzed erythrocytes, large number of lipid droplets and material deposition in sinuzoids in the liver this group were seen. Presented study showed that the brodifacoum causes cellular abnormalities of rat liver