Araştırma Makalesi
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Simvastatin’in Fare (Mus musculus C. Linnaeus) Karaciğeri Üzerine Etkilerinin Histopatolojik Yöntemler ile Araştırılması

Yıl 2017, Cilt: 10 Sayı: 2, 245 - 251, 31.12.2017

Öz

Bu
çalışmada, oral yolla Simvastatin uygulamasının fare (Mus musculus C. Linnaeus)
karaciğer dokusu üzerine etkisi histopatolojik yöntemlerle araştırıldı.
Çalışmada rastgele seçilen 20 erkek fare kullanıldı. I. gruptaki hayvanlara
(Kontrol) (n:10) deney süresince normal çeşme suyu içirildi. II. gruptaki
hayvanlara (Simvastatin) (n:10) 30 gün boyunca içme sularına 20 mg/kg
simvastatin uygulandı. Simvastatin uygulanan hayvanların Kontrol grubundaki
hayvanlara oranla daha az yem ve su tükettiği gözlendi. Operasyon sırasında
simvastatin uygulanan hayvanların genelinde (7/10) abdomenlerindeki periton
boşluğu ve bağırsak etrafında yoğun olarak yağ dokusu izlenirken az bir
kısmında (3/10) hiç gözlenemedi. Mikroskobik veriler sonucunda yapmış olduğumuz
preparatların tümü incelendiğinde kontrol grubundaki hayvanların genel olarak
karaciğer dokusunda histopatolojik bir bulgu saptanmadı, hepatositler ve
sinozoidal yapının normal görünümde olduğu gözlemlendi. Simvastatin uygulanan
gruptaki hayvanların karaciğerler dokularından elde edilen preparatlarda ise Vena centralisi oluşturan damar
duvarının tek katlı yassı epiteli normal görünümde olduğu ancak duvarında
yıkımlar tespit edildi. Ayrıca V. centralislere yakın konumdaki karaciğer
parankiması içerisinde mononükleer hücre infiltrasyonları (MHI), hepatik
hücrelerde fokal nekroz alanları, piknotikleşmiş nükleuslar ve vakuoler
dejenerasyonlar gözlemlendi. Ayrıca kupfferin fagositik hücre çekirdekleri de
izlenebiliyordu.

Kaynakça

  • Adik, A. (2006). Nonalkolik Karaciğer Yağlanmasında Statin Tedavisinin Karaciğer Enzim Profili Üzerine Olan Etkileri. T.C. Haydarpaşa Numune Hastanesi, İç Hastalıkları Kliniği.
  • Arslan, G. (2008. Yüksek dozda Simvastatin’in ratlarda oluşturduğu hepatotoksisite üzerine N-asetil sistein’in etkisi. Selçuk Üniversitesi, Sağlık Bilimleri Enstitüsü.
  • Bilheimer, D. W., Grundy, S. M., Brown, M. S., ve Goldstein, J. L. (1983). Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proceedings of the National Academy of Sciences of the United States of America, 80 (13), 4124–4128.
  • Chalasani, N. (2005). Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology (Baltimore, Md.), 41 (4), 690–695.
  • Crawford, M. ve DiMarco, J. (2003). Hiperlipidemi tedavisi. Içinde: Crawford Kardiyoloji. 1–18.
  • Dujovne, C. A. (2002). Side effects of statins: hepatitis versus “transaminitis”-myositis versus “CPKitis”. The American Journal of Cardiology, 89 (12), 1411–1413.
  • Endo, A. (1992). The discovery and development of HMG-CoA reductase inhibitors. Journal of Lipid Research, 33 (11), 1569–1582.
  • Gotto, A. M. (2006). Statins, Cardiovascular Disease, and Drug Safety. The American Journal of Cardiology, 97 (8, Supplement 1), S3–S5.
  • Hatzitolios, A. Savopoulos, C., Lazaraki, G., Sidiropoulos, I., Haritanti, P., Lefkopoulos, A., Karagiannopoulou, G., Tzioufa, V., ve Dimitrios, K., (2004). Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia. Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology, 23 (4), 131–134.
  • Hsiang, B., Zhu, Y., Wang, Z., Wu, Y., Sasseville, V., Yang, W. P., ve Kirchgessner, T. G.,(1999). A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. The Journal of Biological Chemistry, 274 (52), 37161–37168.
  • Kiortsis, D. N., Nikas, S., Hatzidimou, K., Tsianos, E., ve Elisaf, M. S. (2003). Lipid-lowering drugs and serum liver enzymes: the effects of body weight and baseline enzyme levels. Fundamental & Clinical Pharmacology, 17 (4), 491–494.
  • Kiyici, M., Gulten, M., Gurel, S., Nak, S. G., Dolar, E., Savci, G., Adim, S. B., Yerci, O., ve Memik, F. (2003). Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis. Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie, 17 (12), 713–718.
  • LaRosa, J. C., He, J., ve Vupputuri, S. (1999). Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA, 282 (24), 2340–2346.
  • Mahmoudi, M., Gorenne, I., Mercer, J., Figg, N., Littlewood, T., ve Bennett, M. (2008). Statins use a novel Nijmegen breakage syndrome-1-dependent pathway to accelerate DNA repair in vascular smooth muscle cells. Circulation Research, 103 (7), 717–725.
  • Rallidis, L. S., Drakoulis, C. K., ve Parasi, A. S. (2004). Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis, 174 (1), 193–196.
  • Topol, E. J. (2004). Intensive Statin Therapy — A Sea Change in Cardiovascular Prevention. New England Journal of Medicine, 350 (15), 1562–1564.
  • Yang, H., Choi, M.-J., Wen, H., Kwon, H. N., Jung, K. H., Hong, S.-W., Kim, J. M., Hong, S.-S., ve Park, S. (2011). An Effective Assessment of Simvastatin-Induced Toxicity with NMR-Based Metabonomics Approach. PLOS ONE, 6 (2), e16641.

Simvastatin, Mouse (Mus musculus C. Linnaeus) to Investigate Methods and Histopathological Effects on The Liver

Yıl 2017, Cilt: 10 Sayı: 2, 245 - 251, 31.12.2017

Öz

In this
study, oral administration of simvastatin application mouse (Mus musculus
Linnaeus C.) The effect of liver tissue was investigated using
histopathological methods. In the study by using randomly selected 20 male
mouse in each group located in 10 mouse a control (I. group) and one
experimental (II. group) group was created. Tap water was given to th animals
in I. group and tap water containing simvastatin (20mg/kg) was given to the
animals in II. group for 30 days. Simvastatin in the animals, feed and water
consumed in the control group were less than animals. Subjects were decapitated
and liver samples were collected from the method of cerebral dislocation.
During the operation the animals in the simvastatin (7/10) fat 
concentrated
around the abdomen, the peritoneal cavity and intestinal observed, a small
proportion (3/10) were observed at all. As a result of the microscopic data, we
have done all the preparations examined, the control group of animals in
general, a histopathologic findings were detected in liver tissue, was observed
in hepatocytes and sinusoidal structure is normal. Preparations obtained from
liver tissues of animals administered with simvastatin group forming the vena centralis is normal squamous
epithelium of the vessel wall but the wall of the destruction was detected. In
addition, mononuclear cell infiltration in the liver parenchyma close to the vena centralis (MHI), hepatic cells,
focal necrosis, pyknotic nuclei and vacuolar degeneration was observed. In
addition, the phagocytic Kupffer cells were observed in cores.

Kaynakça

  • Adik, A. (2006). Nonalkolik Karaciğer Yağlanmasında Statin Tedavisinin Karaciğer Enzim Profili Üzerine Olan Etkileri. T.C. Haydarpaşa Numune Hastanesi, İç Hastalıkları Kliniği.
  • Arslan, G. (2008. Yüksek dozda Simvastatin’in ratlarda oluşturduğu hepatotoksisite üzerine N-asetil sistein’in etkisi. Selçuk Üniversitesi, Sağlık Bilimleri Enstitüsü.
  • Bilheimer, D. W., Grundy, S. M., Brown, M. S., ve Goldstein, J. L. (1983). Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proceedings of the National Academy of Sciences of the United States of America, 80 (13), 4124–4128.
  • Chalasani, N. (2005). Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology (Baltimore, Md.), 41 (4), 690–695.
  • Crawford, M. ve DiMarco, J. (2003). Hiperlipidemi tedavisi. Içinde: Crawford Kardiyoloji. 1–18.
  • Dujovne, C. A. (2002). Side effects of statins: hepatitis versus “transaminitis”-myositis versus “CPKitis”. The American Journal of Cardiology, 89 (12), 1411–1413.
  • Endo, A. (1992). The discovery and development of HMG-CoA reductase inhibitors. Journal of Lipid Research, 33 (11), 1569–1582.
  • Gotto, A. M. (2006). Statins, Cardiovascular Disease, and Drug Safety. The American Journal of Cardiology, 97 (8, Supplement 1), S3–S5.
  • Hatzitolios, A. Savopoulos, C., Lazaraki, G., Sidiropoulos, I., Haritanti, P., Lefkopoulos, A., Karagiannopoulou, G., Tzioufa, V., ve Dimitrios, K., (2004). Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia. Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology, 23 (4), 131–134.
  • Hsiang, B., Zhu, Y., Wang, Z., Wu, Y., Sasseville, V., Yang, W. P., ve Kirchgessner, T. G.,(1999). A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. The Journal of Biological Chemistry, 274 (52), 37161–37168.
  • Kiortsis, D. N., Nikas, S., Hatzidimou, K., Tsianos, E., ve Elisaf, M. S. (2003). Lipid-lowering drugs and serum liver enzymes: the effects of body weight and baseline enzyme levels. Fundamental & Clinical Pharmacology, 17 (4), 491–494.
  • Kiyici, M., Gulten, M., Gurel, S., Nak, S. G., Dolar, E., Savci, G., Adim, S. B., Yerci, O., ve Memik, F. (2003). Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis. Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie, 17 (12), 713–718.
  • LaRosa, J. C., He, J., ve Vupputuri, S. (1999). Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA, 282 (24), 2340–2346.
  • Mahmoudi, M., Gorenne, I., Mercer, J., Figg, N., Littlewood, T., ve Bennett, M. (2008). Statins use a novel Nijmegen breakage syndrome-1-dependent pathway to accelerate DNA repair in vascular smooth muscle cells. Circulation Research, 103 (7), 717–725.
  • Rallidis, L. S., Drakoulis, C. K., ve Parasi, A. S. (2004). Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis, 174 (1), 193–196.
  • Topol, E. J. (2004). Intensive Statin Therapy — A Sea Change in Cardiovascular Prevention. New England Journal of Medicine, 350 (15), 1562–1564.
  • Yang, H., Choi, M.-J., Wen, H., Kwon, H. N., Jung, K. H., Hong, S.-W., Kim, J. M., Hong, S.-S., ve Park, S. (2011). An Effective Assessment of Simvastatin-Induced Toxicity with NMR-Based Metabonomics Approach. PLOS ONE, 6 (2), e16641.
Toplam 17 adet kaynakça vardır.

Ayrıntılar

Konular Mühendislik
Bölüm Makaleler
Yazarlar

Hasan Asker 0000-0002-5703-2164

Yusuf Ersan

Yayımlanma Tarihi 31 Aralık 2017
Gönderilme Tarihi 27 Aralık 2017
Yayımlandığı Sayı Yıl 2017 Cilt: 10 Sayı: 2

Kaynak Göster

APA Asker, H., & Ersan, Y. (2017). Simvastatin’in Fare (Mus musculus C. Linnaeus) Karaciğeri Üzerine Etkilerinin Histopatolojik Yöntemler ile Araştırılması. Kafkas Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 10(2), 245-251.