Evaluation Of The Atorvastatin-Induced Structural Changes In Skeletal Muscles Of Rats By Light Microscope

Abstract

In this study we evaluated toxic effects of atorvastatin on the development of muscle necrosis in rats at the light microscopic level .Male, adult 40 Wistar- albino rat used in this study. Rats divided into 10 equal groups as one control, 9 treatment groups. All rats were sacrified after 5th 10th and 15th days of the study.And their quadriceps femoris muscle tissues were examined in light microscopy. In control group there was no histopatologic changes determined on their muscle tissue samples. But on the other hand, in the treatment groups, some histopathologic changes were determined in different degrees. Generally our findings were degenaration, contraction, necrosis, fibrosis in the perimisial area, central nucleus on the muscle tissues. These findings were increased due to the high treatment dose and the long treatment time. Histopathologic changes were increased due to the high treatment dose and the long treatment time. Because of all these reasons, medical doctors will take care about the treatment dose and the long treatment time of the atorvastatin.

Keywords

• Atorvastatin, rat, muscle necrosis, histopathology.

Atorvastatinin Sıçan skelet Kasında Olusturdugu Yapısal Degisikliklerin Isık Mikroskobu le Degerlendirilmesi

Abstract

Çalısmamızda, bir statin türevi olan atorvastatinin sıçan iskelet kasında olusturdugu yapısal degisikliklerinısık mikroskobu düzeyinde incelenmesi ve degerlendirilmesi amaçlandı.40 adet eriskin erkek wistar albinorat; biri kontrol ve dokuzu deney grupları olmak üzere 10 esit gruba bölündü. . Deneyin baslamasındansonra 5. 10. ve 15. günlerde sakrifiye edilen ratların quadriceps femoris kasları ısık mikroskobundaincelendi. Kontrol grubundan elde edilen kasların histopatolojik incelemelerinde herhangi bir yapısaldegisiklige rastlanmazken, diger 9 deney grubundan elde edilen kas örneklerinde degisen derecelerdehistopatolojik bulgular elde edildi. Genel olarak kaslarda dejenerasyon, kontraksiyon, nekroz, bagdokuartısı, mononükleer hücre infiltrasyonu, kas lifleri arasında vakuoler yapılar ve sentral nükleus belirgin artısgöstermekteydi. Çalısmamızda bulgularımız, doz ve zaman arttıkça degisikliklerin belirgin oldugugözlendi. Atorvastatinin iskelet kaslarında göstermis oldugu toksik etki ile birlikte, klinik açıdan doz vezaman baz alınarak, hasta tedavilerine ısık tutacagı kanaatine varıldı.

Keywords

• Atorvastatin, sıçan, kas nekrozu, histopatoloji.

References

1. Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rabdomyolysis in patients treated with 2004;292:2585-90. drugs. JAMA
2. Shek A and Ferril MJ. Statin-fibrate combination therapy. Ann Pharmacother 2001;35:908-17
3. Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother 2002;36:288-95.
4. Thompson PD, Clarkson P, Karas RH. Statin- associated myopathy. JAMA. 2003;289:1681-90.
5. Bennett W E, Drake AJ 3rd and Shakir KM. Reversible myopathy after statin therapy in patients with normal creatine kinase levels. Ann Intern Med 2003;138: 436–7.
6. Phillips PS, Haas RH, Bannykh S,et al. Statin- associated myopathy with normal creatine kinase levels. Ann Intern Med 2002;137:581-5
7. Beyer RE. An analysis of the role of coenzyme Q in free radical generation and as an antioxidant. Biochem Cell Biol 1992;70.390– 403.
8. Rosenson RS, Lowe GD. Effects of lipids and lipoproteins On thrombosis and rheology. Atherosclerosis 1998;140:271–80.

9. Maron DJ, Fazio S, Linton MF. Current perspectives 2000;101:207-213. Circulation
10. Baker SK, Tarnopolsky MA. Statin myopathies: pathophysiologic and clinical perspectives. Clin Invest Med 2001;24;258-272.
11. Rousseau G, Desrosiers C, Varin F. A comparison of the effects of lovastatin and pravastatin on ubiquinone tissue levels in rats. Curr Ther Res 1998;59: 666-679.
12. Thelin A, Schedin S, Dallner G. Half-life of ubiquinone-9 in rat tissues. FEBS Lett 1992; 313:118–121.
13. von-Keutz E, Schluter G. Preclinical safety evaluation of cerivastatin, a novel HMG-CoA reductase inhibitor. Am J Cardiol 1998;82;11J- 17J.
14. Manfredi G, Spinazzola A, Checcarelli N, Naini A. Assay of mitochondrial ATP synthesis in animal cells. Methods Cell Biol 2001; 65, 139- 141.
15. Smith PF, Eydelloth RS, Grossman SJ, et al. HMG-CoA myopathy in the rat: cyclosporine A interaction and mechanism studies. J. Pharmacol Exp Ther 1991; 257;1225- 1235. inhibitor-induced
16. William H, Jeffery W, Amy F, et al. Evalution of ubiquinone Concentration and mitochondrial function relative to cerivastatin- induced skeletal myopathy in rats.Toxicol Applied Pharmacol 2004;194 10-23.
17. Andrew JW,Sıgurd L,Andrew G.Experimental lovastatin myopathy. J Neuropathol Exp Neurol 1993;542-549.