Wistar Ratlarında Dietilnitrozamin Uygulanarak Oluşturulan Hepatoselüler Karsinom Modelinde Silimarin’in Koruyucu Etkisi; Kanser Paternleri ve Sitolojik Varyantlar
Year 2020,
Volume: 15 Issue: 1, 43 - 50, 30.04.2020
Emin Karakurt
,
Serpil Dağ
Abstract
Bu çalışmada, ratlarda deneysel olarak Dietilnitrozamin uygulanarak oluşturulan Hepatoselüler karsinom modelinde Silimarin’in koruyucu etkisi kanser paternleri ve sitolojik varyantlar açısından histopatolojik metodlarla araştırılmıştır. Bu amaçla ratlar 5 gruba ayrıldı. Kontrol grubundaki ratlara 20 hafta boyunca pelet yem ve içme suyu verildi. Sham grubundaki hayvanlara %0.9 NaCl içerisinde çözdürülmüş propilen glikol intraperitoneal yolla haftada 3 kez olmak üzere 20 hafta boyunca verildi. DEN grubundaki hayvanlara 50 mg/kg dozunda haftada 1 kez olmak üzere 20 hafta boyunca DEN uygulaması yapıldı. DEN+Silimarin grubundaki ratlara DEN uygulamasından 1 hafta önce başlayacak şekilde 100 mg/kg dozunda haftada 3 kez olmak üzere 21 hafta boyunca intraperitoneal yolla Silimarin uygulandı. Silimarin grubundaki ratlara 100 mg/kg dozunda 20 hafta boyunca intraperitoneal yolla haftada 3 kez olmak üzere Silimarin uygulandı. Çalışmanın sonunda, hayvanların sistemik nekropsisi yapıldı ve karaciğer doku örnekleri alındı. Rutin doku takip işlemlerinden sonra kesitler ışık mikroskobu altında değerlendirildi. DEN ve DEN+Silimarin gruplarında Hepatoselüler karsinom oluştuğunu gözlemledik
Supporting Institution
KAÜ Bilimsel Araştırma Projeleri Koordinatörlüğü
Project Number
2016-TS-08
References
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4. Salama YA., El-Karef A., El Gayyar AM., Abdel-Rahman N., 2019. Beyond its antioxidant properties: Quercetin targets multiple signalling pathways in hepatocellular carcinoma in rats. Life Sci, 236, 116933.
5. Subramaniam N., Kannan PKA., Thiruvengadam D., 2019. Hepatoprotective effect of boldine against diethylnitrosamine-induced hepatocarcinogenesis in wistar rats. J Biochem Mol Toxicol, 33, e22404.
6. Rawla P., Sunkara T., Muralidharan P., Raj JP., 2018. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn), 22, 141-150.
7. Fahmi A., Hassanen N., Abdur-Rahman M., Shams-Eldin E., 2019. Phytochemicals, antioxidant activity and hepatoprotective effect of ginger (Zingiber officinale) on diethylnitrosamine toxicity in rats. Biomarkers, 24, 436-447.
8. Moawed FS., El-Sonbaty SM., Mansour SZ., 2019. Gallium nanoparticles along with low-dose gamma radiation modulate TGF-β/MMP-9 expression in hepatocellular carcinogenesis in rats. Tumour Biol, 41, 1010428319834856.
9. Bosch-Barrera J., Menendez JA., 2015. Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy. Cancer Treat Rev, 41, 540-546.
10. Anwar S., Madkor HR., Ahmed N., Wagih ME., 2018. In vivo anticlastogenic effect of silymarin from milk thistle Silybum marianum L. Indian J Pharmacol, 50, 108-115.
11. Cullen JM., 2017. Tumors of the Liver and Gallbladder. In ‘’Tumors in Domestic Animals’’, Ed., DJ Meuten, 5th ed., 602-622, Wiley Blackwell, Iowa.
12. Geller SA., Petrowic LM., 2009. Primary and Metastatic Malignant Tumors of the Liver. In ‘’Biopsy Interpretation of the Liver’’, Ed., SA Geller, LM Petrowic, 2nd ed., 319-368, Lippincott Williams & Wilkins, Philadelphia.
13. Washington K., Harris E., 2010. Masses of the Liver. In ‘’Sternberg's Diagnostic Surgical Pathology’’, Ed., SE Mills, 5th ed., 1536-1594, Lippincott Williams &Wilkins, Philadelphia.
14. Ferrell L., Kakar S., 2013. Tumors of the Liver, Biliary Tree, and Gallbladder. In ‘’ Diagnostic Histopathology of Tumors: Vol 1’’, Ed., CDM Fletcher, 4th ed., 477-530, Elsevier Saunder, Philadelphia.
15. Hirohashi S., Ishak KG., Kojiro M., Wanless IR., Theise ND., Tsukuma H., Blum HE., Deugnier Y., Laurent Puig P., Fischer HP., Sakamoto M., 2000. Tumours of the liver and intrahepatic bile ducts. In ‘’ World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Digestive System‘’, Ed., SR Hamilton, LA Aaltonen, 157-202, IARC Press, Lyon.
16. Salomao M., McMillen E., Lefkowitch JH., 2012. Recent advances in the classification of hepatocellular carcinoma. Diagnostic Histopathol, 18, 37-45.
17. Schlageter M., Terracciano LM., D’Angelo S., Sorrentino P., 2014. Histopathology of hepatocellular carcinoma. World J Gastroenterol, 20, 15955-15964.
18. Goodman ZD., Terracciano LM., Wee A., 2012. Tumours and tumour-like lesions of the liver. In ‘’MacSween's Pathology of the Liver’’, Ed., AD Burt, BC Portmann, LD Ferrell, 761-851, 6th ed., Churchill Livingstone Elsevier, Edinburgh.
19. Ramakrishnan G., Raghavendran HR., Vinodhkumar R., Devaki T., 2006. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem Biol Interact, 161, 104-114.
20. El Mesallamy HO., Metwally NS., Soliman MS., Ahmed KA., Abdel Moaty MM., 2011. The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats. Cancer Cell Int, 11, 38.
21. Hussain T., Siddiqui HH., Fareed S., Vijayakumar M., Rao CV., 2012. Evaluation of chemopreventive effect of Fumaria indica against N-nitrosodiethylamine and CCl4-induced hepatocellular carcinoma in Wistar rats. Asian Pac J Trop Med, 5, 623-629.
22. Arul D., Subramanian P., 2013. Inhibitory effect of naringenin (citrus flavonone) on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Biochem Biophys Res Commun, 434, 203-209.
23. Cui LM., Zhang K., DJ Ma., Liu SP., Zhang XW., 2014. Protein expression under sustained activation of signal transducer and activator of transcription-3 in diethylnitrosamine-induced rat liver carcinogenesis. Oncol Lett, 8, 608-614.
24. Song S., Yuan P., Li P., Wu H., Lu J., Wei W., 2014. Dynamic analysis of tumor-associated immune cells in DEN-induced rat hepatocellular carcinoma. Int Immunopharmacol, 22, 392-399.
25. de Guadalupe Chavez-Lopez M., Perez-Carreon JI., Zuniga-Garcia V., Diaz-Chavez J., Herrera LA., Caro-Sanchez CH., Acuna-Macias I., Gariglio P., Hernandez-Gallegos E., Chiliquinga AJ., Camacho J., 2015. Astemizole-based anticancer therapy for hepatocellular carcinoma (HCC), and Eag1 channels as potential early-stage markers of HCC. Tumour Biol, 36, 6149-6158.
26. Liu WH., Ren LN., Wang X., Wang T., Zhang N., Gao Y., Luo H., Navarro-Alvarez N., Tang LJ., 2015. Combination of exosomes and circulating micro RNAs may serve as a promising tumor marker complementary to alpha-fetoprotein for early-stage hepatocellular carcinoma diagnosis in rats. J Cancer Res Clin Oncol, 141, 1767-1778.
27. Zuniga-Garcia V., Chavez-LopezMde G., Quintanar-Jurado V., Gabino-Lopez NB., Hernandez-Gallegos E., Soriano-Rosas J., Perez-Carreon JI., Camacho J., 2015. Differential Expression of Ion Channels and Transporters During Hepatocellular Carcinoma Development. Dig Dis Sci, 60, 2373-2383.
28. Kadasa NM., Abdallah H., Afifi M., Gowayed S., 2015. Hepatoprotective effects of curcumin against diethyl nitrosamine induced hepatotoxicity in albino rats. Asian Pac J Cancer Prev, 16, 103-108.
29. Shaarawy SM., Tohamy AA., Elgendy SM., Elmageed ZY., Bahnasy A., Mohamed MS., Kandil E., Matrougui K., 2009. Protective effects of garlic and silymarin on NDEA-induced rats hepatotoxicity. Int J Biol Sci, 5, 549-557.
30. Linza A., Wills PJ., Ansil PN., Prabha SP., Nitha A., Latha B., Sheeba KO., Latha MS., 2013. Dose-response effects of Elephantopus scaber methanolic extract on N-nitrosodiethylamine-induced hepatotoxicity in rats. Chin J Nat Med, 11, 362-370.
Protective Effect of Silymarin on Diethylnitrosamine Induced Hepatocellular Carcinoma Model in Wistar Rats; Cancer Patterns and Cytological Variants
Year 2020,
Volume: 15 Issue: 1, 43 - 50, 30.04.2020
Emin Karakurt
,
Serpil Dağ
Abstract
In this study, the protective effect of silymarin was investigated with histopathological methods in terms of cancer patterns and cytological variants in the hepatocellular carcinoma model created by applying diethylnitrosamine experimentally in rats. For this purpose, the rats were randomly divided into 5 groups. The rats in the control group were fed pellet feed and drinking water for 20 weeks. Animals in Sham group were administered with propylene glycol dissolved in 0.9% NaCl intraperitoneally 3 times a week for 20 weeks. Animals in DEN group administered DEN at a dose of 50 mg/kg once a week for 20 weeks. The rats in the DEN +Silymarin group were Silymarin intraperitoneally administered for 21 weeks 3 times a week at a dose of 100 mg/kg, starting 1 week prior to the administration of DEN. Silymarin was administered to rats in the group of Silymarin 3 times a week intraperitoneally for 20 weeks at a dose of 100 mg/kg. At the end of the study, systemic necropsy of the animals was performed and liver tissue samples were taken. After routine tissue procedures, sections were examined under the light microscope. We observed that Hepatocellular carcinoma occurred in DEN and DEN + Silymarin groups.
Project Number
2016-TS-08
References
- 1. Medhat A., Mansour S., El-Sonbaty S., Kandil E., Mahmoud M., 2017. Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats. Tumour Biol, 39,1-10.
2. Elsayed MM., Mostafa ME., Alaaeldin E., Sarhan HA., Shaykoon MS., Allam S., Ahmed AR., Elsadek BE., 2019. Design and characterisation of novel sorafenib-loaded carbon nanotubes with distinct tumour-suppressive activity in hepatocellular carcinoma. Int J Nanomedicine, 14, 8445-8467.
3. Livingstone MC., Johnson NM., Roebuck BD., Kensler TW., Groopman JD., 2019. Serum miR-182 is a predictive biomarker for dichotomization of risk of hepatocellular carcinoma in rats. Mol Carcinog, 58, 2017-2025.
4. Salama YA., El-Karef A., El Gayyar AM., Abdel-Rahman N., 2019. Beyond its antioxidant properties: Quercetin targets multiple signalling pathways in hepatocellular carcinoma in rats. Life Sci, 236, 116933.
5. Subramaniam N., Kannan PKA., Thiruvengadam D., 2019. Hepatoprotective effect of boldine against diethylnitrosamine-induced hepatocarcinogenesis in wistar rats. J Biochem Mol Toxicol, 33, e22404.
6. Rawla P., Sunkara T., Muralidharan P., Raj JP., 2018. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn), 22, 141-150.
7. Fahmi A., Hassanen N., Abdur-Rahman M., Shams-Eldin E., 2019. Phytochemicals, antioxidant activity and hepatoprotective effect of ginger (Zingiber officinale) on diethylnitrosamine toxicity in rats. Biomarkers, 24, 436-447.
8. Moawed FS., El-Sonbaty SM., Mansour SZ., 2019. Gallium nanoparticles along with low-dose gamma radiation modulate TGF-β/MMP-9 expression in hepatocellular carcinogenesis in rats. Tumour Biol, 41, 1010428319834856.
9. Bosch-Barrera J., Menendez JA., 2015. Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy. Cancer Treat Rev, 41, 540-546.
10. Anwar S., Madkor HR., Ahmed N., Wagih ME., 2018. In vivo anticlastogenic effect of silymarin from milk thistle Silybum marianum L. Indian J Pharmacol, 50, 108-115.
11. Cullen JM., 2017. Tumors of the Liver and Gallbladder. In ‘’Tumors in Domestic Animals’’, Ed., DJ Meuten, 5th ed., 602-622, Wiley Blackwell, Iowa.
12. Geller SA., Petrowic LM., 2009. Primary and Metastatic Malignant Tumors of the Liver. In ‘’Biopsy Interpretation of the Liver’’, Ed., SA Geller, LM Petrowic, 2nd ed., 319-368, Lippincott Williams & Wilkins, Philadelphia.
13. Washington K., Harris E., 2010. Masses of the Liver. In ‘’Sternberg's Diagnostic Surgical Pathology’’, Ed., SE Mills, 5th ed., 1536-1594, Lippincott Williams &Wilkins, Philadelphia.
14. Ferrell L., Kakar S., 2013. Tumors of the Liver, Biliary Tree, and Gallbladder. In ‘’ Diagnostic Histopathology of Tumors: Vol 1’’, Ed., CDM Fletcher, 4th ed., 477-530, Elsevier Saunder, Philadelphia.
15. Hirohashi S., Ishak KG., Kojiro M., Wanless IR., Theise ND., Tsukuma H., Blum HE., Deugnier Y., Laurent Puig P., Fischer HP., Sakamoto M., 2000. Tumours of the liver and intrahepatic bile ducts. In ‘’ World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Digestive System‘’, Ed., SR Hamilton, LA Aaltonen, 157-202, IARC Press, Lyon.
16. Salomao M., McMillen E., Lefkowitch JH., 2012. Recent advances in the classification of hepatocellular carcinoma. Diagnostic Histopathol, 18, 37-45.
17. Schlageter M., Terracciano LM., D’Angelo S., Sorrentino P., 2014. Histopathology of hepatocellular carcinoma. World J Gastroenterol, 20, 15955-15964.
18. Goodman ZD., Terracciano LM., Wee A., 2012. Tumours and tumour-like lesions of the liver. In ‘’MacSween's Pathology of the Liver’’, Ed., AD Burt, BC Portmann, LD Ferrell, 761-851, 6th ed., Churchill Livingstone Elsevier, Edinburgh.
19. Ramakrishnan G., Raghavendran HR., Vinodhkumar R., Devaki T., 2006. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem Biol Interact, 161, 104-114.
20. El Mesallamy HO., Metwally NS., Soliman MS., Ahmed KA., Abdel Moaty MM., 2011. The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats. Cancer Cell Int, 11, 38.
21. Hussain T., Siddiqui HH., Fareed S., Vijayakumar M., Rao CV., 2012. Evaluation of chemopreventive effect of Fumaria indica against N-nitrosodiethylamine and CCl4-induced hepatocellular carcinoma in Wistar rats. Asian Pac J Trop Med, 5, 623-629.
22. Arul D., Subramanian P., 2013. Inhibitory effect of naringenin (citrus flavonone) on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Biochem Biophys Res Commun, 434, 203-209.
23. Cui LM., Zhang K., DJ Ma., Liu SP., Zhang XW., 2014. Protein expression under sustained activation of signal transducer and activator of transcription-3 in diethylnitrosamine-induced rat liver carcinogenesis. Oncol Lett, 8, 608-614.
24. Song S., Yuan P., Li P., Wu H., Lu J., Wei W., 2014. Dynamic analysis of tumor-associated immune cells in DEN-induced rat hepatocellular carcinoma. Int Immunopharmacol, 22, 392-399.
25. de Guadalupe Chavez-Lopez M., Perez-Carreon JI., Zuniga-Garcia V., Diaz-Chavez J., Herrera LA., Caro-Sanchez CH., Acuna-Macias I., Gariglio P., Hernandez-Gallegos E., Chiliquinga AJ., Camacho J., 2015. Astemizole-based anticancer therapy for hepatocellular carcinoma (HCC), and Eag1 channels as potential early-stage markers of HCC. Tumour Biol, 36, 6149-6158.
26. Liu WH., Ren LN., Wang X., Wang T., Zhang N., Gao Y., Luo H., Navarro-Alvarez N., Tang LJ., 2015. Combination of exosomes and circulating micro RNAs may serve as a promising tumor marker complementary to alpha-fetoprotein for early-stage hepatocellular carcinoma diagnosis in rats. J Cancer Res Clin Oncol, 141, 1767-1778.
27. Zuniga-Garcia V., Chavez-LopezMde G., Quintanar-Jurado V., Gabino-Lopez NB., Hernandez-Gallegos E., Soriano-Rosas J., Perez-Carreon JI., Camacho J., 2015. Differential Expression of Ion Channels and Transporters During Hepatocellular Carcinoma Development. Dig Dis Sci, 60, 2373-2383.
28. Kadasa NM., Abdallah H., Afifi M., Gowayed S., 2015. Hepatoprotective effects of curcumin against diethyl nitrosamine induced hepatotoxicity in albino rats. Asian Pac J Cancer Prev, 16, 103-108.
29. Shaarawy SM., Tohamy AA., Elgendy SM., Elmageed ZY., Bahnasy A., Mohamed MS., Kandil E., Matrougui K., 2009. Protective effects of garlic and silymarin on NDEA-induced rats hepatotoxicity. Int J Biol Sci, 5, 549-557.
30. Linza A., Wills PJ., Ansil PN., Prabha SP., Nitha A., Latha B., Sheeba KO., Latha MS., 2013. Dose-response effects of Elephantopus scaber methanolic extract on N-nitrosodiethylamine-induced hepatotoxicity in rats. Chin J Nat Med, 11, 362-370.