Evaluation of morphological effects on liver tissues of metformin use in rats by light and electron microscopy

Abstract

Metformin is the most commonly prescribed oral anti-diabetic agent for type II diabetes. It is generally considered as a safe drug but it is reported that it may also have a hepatotoxic effect. Studies in the literature evaluating the morphological and ultrastructural effects of metformin on liver tissue are more likely include whether it reduces an experimentally created liver injury. However, this drug can also be used in patients without any liver disease, such as polycystic ovarian syndrome. Our aim in this study is to evaluate whether metformin use causes any change in the liver with the help of light and permeable electron microscopy (TEM) while there is no liver disease. For this purpose, Wistar Albino male rats were divided into two groups as control and metformin groups. Metformin (100mg/kg) was applied to the metformin group for three weeks and an equal volume of saline was given to the control group. Liver samples were taken from rats under ketamine/xylazine anesthesia after one week of the drug-free period and euthanasia was performed. After biopsy, liver samples were taken for routine TEM procedure for light and electron microscopic examinations. Semithin (700 nm) and ultrathin (60 nm) sections from samples were evaluated by firstly light microscope and then Hitachi HT 7800 TEM. While healthy findings including regular hepatocyte, nucleus and nucleolus were observed in the control group samples, abundant vacuol formation, nuclear irregularity and shrinkage, abundant blood vessel and hepatocyte separation were observed in metformin-treated samples. The findings of our study show that metformin may have adverse effects on hepatocytes in long-term use.

Keywords

• Metformin,lver,TEM

Sıçanlarda Metformin Kullanımının Karaciğer Dokuları Üzerine Morfolojik Etkilerinin Işık ve Elektron Mikroskopisi ile Değerlendirilmesi

Abstract

Metformin, tip II diyabet için en sık reçete edilen oral anti-diyabetik ajandır. Genellikle güvenli bir ilaç olarak kabul edilir, ancak hepatotoksik etkisi de olabileceği bildirilmektedir. Literatürde metforminin karaciğer dokusundaki morfolojik ve ultrayapısal etkilerini değerlendiren çalışmalar, daha çok deneysel olarak oluşturulan bir karaciğer hasarını azaltıp azaltmadığı yönündedir. Ancak bu ilaç polikistik over sendromu gibi, herhangi bir karaciğer rahatsızlığı olmayan hastalarda da kullanılabilmektedir. Bu çalışmadaki amacımız herhangi bir karaciğer hastalığı yok iken metformin kullanımının karaciğerde herhangi bir değişime neden olup olmadığını ışık ve geçirimli elektron mikroskopisi yardımı (TEM) ile değerlendirmektir. Bu amaçla Wistar Albino erkek sıçanlar kontrol ve metformin grubu olarak iki gruba ayrılmıştır. Metformin grubuna üç hafta boyunca metformin (100mg / kg) uygulanmış ve kontrol grubuna eşit hacimde serum fizyolojik verilmiştir. Bir haftalık ilaçsız dönemden sonra sıçanlardan ketamin/ksilazin anestezisi altında karaciğer örnekleri alınmış ve ötenazi uygulanmıştır. Biyopsi sonrası karaciğer örnekleri ışık ve elektron mikroskobik incelemeler için rutin TEM takibine alınmışlardır. Örneklerden elde edilen yarı ince (700 nm) ve TEM için alınan tam ince (60 nm) kesitler önce ışık mikroskobu ile sonra da Hitachi HT 7800 TEM ile değerlendirilmiştir. Kontrol grubu örneklerinde düzenli hepatosit, çekirdek ve çekirdekçik içeren sağlıklı bulgular izlenirken, metformin uygulanan örneklerde bol miktarda koful oluşumu, çekirdek düzensizlik ve küçülmeleri, bol kan damarı ve hepatosit ayrılmaları gözlenmiştir. Çalışmamızın bulguları metforminin uzun süreli kullanımda hepatositler üzerinde olumsuz etkileri olabileceğini göstermektedir.

Keywords

• metformin,karaciğer,TEM

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