BibTex RIS Kaynak Göster

Effect of levetiracetam on hepatic fibrosis in diabetic rats

Yıl 2015, Cilt: 1 Sayı: 2, 87 - 93, 17.09.2015
https://doi.org/10.5606/fng.btd.2015.016

Öz

Objectives: In our study we investigated the possible effects of levetiracetam (LEV) on hepatic fibrosis in streptozotocin (STZ) induced diabetic rats with histopathology, real-time elastography imaging technique. We also aimed to investigate the effects of LEV on oxidative stress markers.

Materials and methods: Diabetes was induced by intraperitoneal (i.p.) single dose injection of STZ (60 mg/kg). Twenty-one rats were randomly divided into three groups; control group, STZ group treated with 1 mL/kg/day saline (STZ+SP), and STZ group treated with 600 mg/kg/day LEV was administrated by i.p. for four weeks. All rats underwent a real-time elastography (strain-elasticity %). The liver sections are examined by histopathologically (liver fibrosis score). In addition, malondialdehyde, total antioxidant capacity, and glutathione levels were measured in plasma.

Results: Treatment with LEV significantly decreased liver fibrosis score and increased strain measurement % on the real-time elastography in diabetic rats. In addition, treatment with LEV significantly increased total antioxidant capacity, glutathione and malondialdehyde levels decreased in plasma of diabetic rats.

Conclusion: Levetiracetam has potential as a treatment for diabetic liver injury and hepatic fibrosis and can be a good candidate among new treatment options. In addition, real-time elastography is reliable imaging non-invasive technique for detecting hepatic fibrosis.

Keywords: Diabetes mellitus; levetiracetam; oxidative stress; real-time elastography.

Kaynakça

  • Stone BG, Van Thiel DH. Diabetes mellitus and the liver. Semin Liver Dis 1985;5:8-28.
  • Keeffe EB, Adesman PW, Stenzel P, Palmer RM. Steatosis and cirrhosis in an obese diabetic. Resolution of fatty liver by fasting. Dig Dis Sci 1987;32:441-5.
  • Di Sario A, Candelaresi C, Omenetti A, Benedetti A. Vitamin E in chronic liver diseases and liver fibrosis. Vitam Horm 2007;76:551-73.
  • Parola M, Robino G. Oxidative stress-related molecules and liver fibrosis. J Hepatol 2001;35:297-306.
  • Svegliati-Baroni G, De Minicis S, Marzioni M. Hepatic fibrogenesis in response to chronic liver injury: novel insights on the role of cell-to-cell interaction and transition. Liver Int 2008;28:1052-64.
  • Pinzani M, Rombouts K. Liver fibrosis: from the bench to clinical targets. Dig Liver Dis 2004;36:231-42.
  • Wu YG, Xia LL, Lin H, Zhou D, Qian H, Lin ST. Prevention of early liver injury by breviscapine in streptozotocin-induced diabetic rats. Planta Med 2007;73:433-8.
  • Baydas G, Canatan H, Turkoglu A. Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus. J Pineal Res 2002;32:225-30.
  • de Cavanagh EM, Inserra F, Toblli J, Stella I, Fraga CG, Ferder L. Enalapril attenuates oxidative stress in diabetic rats. Hypertension 2001;38:1130-6.
  • Stettner M, Dehmel T, Mausberg AK, Köhne A, Rose CR, Kieseier BC. Levetiracetam exhibits protective properties on rat Schwann cells in vitro. J Peripher Nerv Syst 2011;16:250-60.
  • Ueda Y, Doi T, Takaki M, Nagatomo K, Nakajima A, Willmore LJ. Levetiracetam enhances endogenous antioxidant in the hippocampus of rats: in vivo evaluation by brain microdialysis combined with ESR spectroscopy. Brain Res 2009;1266:1-7.
  • Gibbs JE, Walker MC, Cock HR. Levetiracetam:
  • antiepileptic properties and protective effects on mitochondrial dysfunction in experimental status epilepticus. Epilepsia 2006;47:469-78.
  • Coppey LJ, Davidson EP, Dunlap JA, Lund DD, Yorek MA. Slowing of motor nerve conduction velocity in streptozotocin-induced diabetic rats is preceded by impaired vasodilation in arterioles that overlie the sciatic nerve. Int J Exp Diabetes Res 2000;1:131-43.
  • Friedrich-Rust M, Ong MF, Herrmann E, Dries V, Samaras P, Zeuzem S, et al. Real-time elastography for noninvasive assessment of liver fibrosis in chronic viral hepatitis. AJR Am J Roentgenol 2007;188:758-64.
  • Kanamoto M, Shimada M, Ikegami T, Uchiyama H, Imura S, Morine Y, et al. Real time elastography for noninvasive diagnosis of liver fibrosis. J Hepatobiliary Pancreat Surg 2009;16:463-7.
  • Demougeot C, Marie C, Beley A. Importance of iron location in iron-induced hydroxyl radical production by brain slices. Life Sci 2000;67:399-410.
  • Benzie IF, Strain JJ. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol 1999;299:15-27.
  • Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.
  • Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998;114:842-5.
  • Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202-19.
  • Clark JM, Diehl AM. Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA 2003;289:3000-4.
  • Maiese K, Morhan SD, Chong ZZ. Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr Neurovasc Res 2007;4:63-71.
  • Leclercq IA, Da Silva Morais A, Schroyen B, Van Hul N, Geerts A. Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. J Hepatol 2007;47:142-56.
  • Das KS, Balakrishnan V, Mukherjee S, Vasudevan DM. Evaluation of blood oxidative stress-related parameters in alcoholic liver disease and non-alcoholic fatty liver disease. Scand J Clin Lab Invest 2008;68:323-34.
  • Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001;344:495-500.
  • Castéra L, Nègre I, Samii K, Buffet C. Pain
  • experienced during percutaneous liver biopsy. Hepatology 1999;30:1529-30.
  • Bedossa P, Dargère D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003;38:1449-57.
  • Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 2002;97:2614-8.
  • Giuseppetti GM, Martegani A, Di Cioccio B,
  • Baldassarre S. Elastosonography in the diagnosis of the nodular breast lesions: preliminary report. Radiol Med 2005;110:69-76.
  • Lin SH, Ma JJ, Zhang H, Ding H, Yu Q, Zhu HG, et al. Real-time elastography for quantitative assessment of liver fibrosis in a rat model. Zhonghua Gan Zang Bing Za Zhi 2012;20:386-9. [Abstract]
  • Niespodziany I, Klitgaard H, Margineanu DG.
  • Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices. Neurosci Lett 2001;306:5-8.
  • Pisani A, Bonsi P, Martella G, De Persis C, Costa C, Pisani F, et al. Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Epilepsia 2004;45:719-28.
  • Madeja M, Margineanu DG, Gorji A, Siep E,
  • Boerrigter P, Klitgaard H, et al. Reduction of voltage- operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action? Neuropharmacology 2003;45:661-71.
  • Poli G, Parola M. Oxidative damage and fibrogenesis. Free Radic Biol Med 1997;22:287-305.

Diyabetik sıçanlarda karaciğer fibrozisi üzerine levetirasetam etkisi

Yıl 2015, Cilt: 1 Sayı: 2, 87 - 93, 17.09.2015
https://doi.org/10.5606/fng.btd.2015.016

Öz

Amaç: Bu çalışmada, streptozotocin (STZ) ile indüklenmiş diyabetik sıçanlardaki hepatik fibrozis üzerine levetirasetamın (LEV) pozitif etkilerinin histopatolojik ve gerçek zamanlı elastografik görüntüleme tekniği ile incelenmesi amaçlandı. Yine bu çalışmada LEV’nin oksidatif stres belirteçleri üzerine etkisi araştırıldı.Gereç ve yöntemler: Diyabetik model, tek doz intraperitoneal (i.p.) STZ (60 mg/kg) enjeksiyonu ile yapıldı. Yirmi bir sıçan rastgele olarak üç gruba ayrıldı; kontrol grubu, STZ uygulaması yapılıp 1 mL/kg/gün salin verilen grup (STZ+SP) ve STZ uygulanıp dört hafta boyunca 600 mg/kg/gün i.p LEV uygulanan grup. Tüm sıçanlar gerçek zamanlı elastografik yöntem ile incelendi (gerilme-elastikiyet yüzdesi). Karaciğerden alınan kesitler histopatolojik olarak değerlendirildi (karaciğer fibroz skoru). Bunlara ek olarak, plazmadan malondialdehit, total antioksidant kapasite ve glutatyon seviyeleri ölçüldü.Bulgular: Levetirasetam ile tedavi edilen diyabetik sıçanlarda karaciğer fibroz skorlamasında anlamlı bir azalma ve gerçek zamanlı elastografik gerilim-elastikiyet yüzdesinde artış saptandı. Bununla birlikte LEV tedavisinde diyabetik sıçanlarda total antioksidant kapasitesinin arttığı, glutatyon ve malondialdehitin plazma seviyelerinin azaldığı görüldü.Sonuç: Levetirasetam, diyabetik karaciğer hasarı ve karaciğer fibrozisi için yeni tedavi seçenekleri arasında iyi bir aday olabilir. Buna ek olarak gerçek zamanlı elastografi, hepatik fibrozisin tespitinde non-invazif ve güvenilir bir görüntüleme bir tekniğidir.

Kaynakça

  • Stone BG, Van Thiel DH. Diabetes mellitus and the liver. Semin Liver Dis 1985;5:8-28.
  • Keeffe EB, Adesman PW, Stenzel P, Palmer RM. Steatosis and cirrhosis in an obese diabetic. Resolution of fatty liver by fasting. Dig Dis Sci 1987;32:441-5.
  • Di Sario A, Candelaresi C, Omenetti A, Benedetti A. Vitamin E in chronic liver diseases and liver fibrosis. Vitam Horm 2007;76:551-73.
  • Parola M, Robino G. Oxidative stress-related molecules and liver fibrosis. J Hepatol 2001;35:297-306.
  • Svegliati-Baroni G, De Minicis S, Marzioni M. Hepatic fibrogenesis in response to chronic liver injury: novel insights on the role of cell-to-cell interaction and transition. Liver Int 2008;28:1052-64.
  • Pinzani M, Rombouts K. Liver fibrosis: from the bench to clinical targets. Dig Liver Dis 2004;36:231-42.
  • Wu YG, Xia LL, Lin H, Zhou D, Qian H, Lin ST. Prevention of early liver injury by breviscapine in streptozotocin-induced diabetic rats. Planta Med 2007;73:433-8.
  • Baydas G, Canatan H, Turkoglu A. Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus. J Pineal Res 2002;32:225-30.
  • de Cavanagh EM, Inserra F, Toblli J, Stella I, Fraga CG, Ferder L. Enalapril attenuates oxidative stress in diabetic rats. Hypertension 2001;38:1130-6.
  • Stettner M, Dehmel T, Mausberg AK, Köhne A, Rose CR, Kieseier BC. Levetiracetam exhibits protective properties on rat Schwann cells in vitro. J Peripher Nerv Syst 2011;16:250-60.
  • Ueda Y, Doi T, Takaki M, Nagatomo K, Nakajima A, Willmore LJ. Levetiracetam enhances endogenous antioxidant in the hippocampus of rats: in vivo evaluation by brain microdialysis combined with ESR spectroscopy. Brain Res 2009;1266:1-7.
  • Gibbs JE, Walker MC, Cock HR. Levetiracetam:
  • antiepileptic properties and protective effects on mitochondrial dysfunction in experimental status epilepticus. Epilepsia 2006;47:469-78.
  • Coppey LJ, Davidson EP, Dunlap JA, Lund DD, Yorek MA. Slowing of motor nerve conduction velocity in streptozotocin-induced diabetic rats is preceded by impaired vasodilation in arterioles that overlie the sciatic nerve. Int J Exp Diabetes Res 2000;1:131-43.
  • Friedrich-Rust M, Ong MF, Herrmann E, Dries V, Samaras P, Zeuzem S, et al. Real-time elastography for noninvasive assessment of liver fibrosis in chronic viral hepatitis. AJR Am J Roentgenol 2007;188:758-64.
  • Kanamoto M, Shimada M, Ikegami T, Uchiyama H, Imura S, Morine Y, et al. Real time elastography for noninvasive diagnosis of liver fibrosis. J Hepatobiliary Pancreat Surg 2009;16:463-7.
  • Demougeot C, Marie C, Beley A. Importance of iron location in iron-induced hydroxyl radical production by brain slices. Life Sci 2000;67:399-410.
  • Benzie IF, Strain JJ. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol 1999;299:15-27.
  • Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.
  • Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998;114:842-5.
  • Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202-19.
  • Clark JM, Diehl AM. Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA 2003;289:3000-4.
  • Maiese K, Morhan SD, Chong ZZ. Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr Neurovasc Res 2007;4:63-71.
  • Leclercq IA, Da Silva Morais A, Schroyen B, Van Hul N, Geerts A. Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. J Hepatol 2007;47:142-56.
  • Das KS, Balakrishnan V, Mukherjee S, Vasudevan DM. Evaluation of blood oxidative stress-related parameters in alcoholic liver disease and non-alcoholic fatty liver disease. Scand J Clin Lab Invest 2008;68:323-34.
  • Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001;344:495-500.
  • Castéra L, Nègre I, Samii K, Buffet C. Pain
  • experienced during percutaneous liver biopsy. Hepatology 1999;30:1529-30.
  • Bedossa P, Dargère D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003;38:1449-57.
  • Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 2002;97:2614-8.
  • Giuseppetti GM, Martegani A, Di Cioccio B,
  • Baldassarre S. Elastosonography in the diagnosis of the nodular breast lesions: preliminary report. Radiol Med 2005;110:69-76.
  • Lin SH, Ma JJ, Zhang H, Ding H, Yu Q, Zhu HG, et al. Real-time elastography for quantitative assessment of liver fibrosis in a rat model. Zhonghua Gan Zang Bing Za Zhi 2012;20:386-9. [Abstract]
  • Niespodziany I, Klitgaard H, Margineanu DG.
  • Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices. Neurosci Lett 2001;306:5-8.
  • Pisani A, Bonsi P, Martella G, De Persis C, Costa C, Pisani F, et al. Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Epilepsia 2004;45:719-28.
  • Madeja M, Margineanu DG, Gorji A, Siep E,
  • Boerrigter P, Klitgaard H, et al. Reduction of voltage- operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action? Neuropharmacology 2003;45:661-71.
  • Poli G, Parola M. Oxidative damage and fibrogenesis. Free Radic Biol Med 1997;22:287-305.
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Deneysel Çalışma
Yazarlar

Yiğit Uyanıkgil

Tülay Akman Bu kişi benim

İbrahim Çavuşoğlu Bu kişi benim

Erkan Kısmalı Bu kişi benim

Dilek Taşkıran Bu kişi benim

Oytun Erbaş

Yayımlanma Tarihi 17 Eylül 2015
Yayımlandığı Sayı Yıl 2015 Cilt: 1 Sayı: 2

Kaynak Göster

APA Uyanıkgil, Y., Akman, T., Çavuşoğlu, İ., Kısmalı, E., vd. (2015). Effect of levetiracetam on hepatic fibrosis in diabetic rats. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, 1(2), 87-93. https://doi.org/10.5606/fng.btd.2015.016
AMA Uyanıkgil Y, Akman T, Çavuşoğlu İ, Kısmalı E, Taşkıran D, Erbaş O. Effect of levetiracetam on hepatic fibrosis in diabetic rats. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. Eylül 2015;1(2):87-93. doi:10.5606/fng.btd.2015.016
Chicago Uyanıkgil, Yiğit, Tülay Akman, İbrahim Çavuşoğlu, Erkan Kısmalı, Dilek Taşkıran, ve Oytun Erbaş. “Effect of Levetiracetam on Hepatic Fibrosis in Diabetic Rats”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 1, sy. 2 (Eylül 2015): 87-93. https://doi.org/10.5606/fng.btd.2015.016.
EndNote Uyanıkgil Y, Akman T, Çavuşoğlu İ, Kısmalı E, Taşkıran D, Erbaş O (01 Eylül 2015) Effect of levetiracetam on hepatic fibrosis in diabetic rats. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 1 2 87–93.
IEEE Y. Uyanıkgil, T. Akman, İ. Çavuşoğlu, E. Kısmalı, D. Taşkıran, ve O. Erbaş, “Effect of levetiracetam on hepatic fibrosis in diabetic rats”, İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, c. 1, sy. 2, ss. 87–93, 2015, doi: 10.5606/fng.btd.2015.016.
ISNAD Uyanıkgil, Yiğit vd. “Effect of Levetiracetam on Hepatic Fibrosis in Diabetic Rats”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 1/2 (Eylül 2015), 87-93. https://doi.org/10.5606/fng.btd.2015.016.
JAMA Uyanıkgil Y, Akman T, Çavuşoğlu İ, Kısmalı E, Taşkıran D, Erbaş O. Effect of levetiracetam on hepatic fibrosis in diabetic rats. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. 2015;1:87–93.
MLA Uyanıkgil, Yiğit vd. “Effect of Levetiracetam on Hepatic Fibrosis in Diabetic Rats”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, c. 1, sy. 2, 2015, ss. 87-93, doi:10.5606/fng.btd.2015.016.
Vancouver Uyanıkgil Y, Akman T, Çavuşoğlu İ, Kısmalı E, Taşkıran D, Erbaş O. Effect of levetiracetam on hepatic fibrosis in diabetic rats. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. 2015;1(2):87-93.