The Effect of Red Reishi Mushroom (Ganoderma lucidum) Extract on Carbon Tetrachloride Induced Liver Injury and Cyclooxygenase-2 Immunoreactivity

Halime Yavuz; Gökhan Nur; H. Ahmet Deveci; İzzettin Güler

doi:10.18016/ksutarimdoga.vi.1196713

TR EN

Kırmızı Reishi Mantarı (Ganoderma lucidum) Extratının Karbon Tetraklorür ile İndüklenen Karaciğer Hasarı ve Siklooksijenaz-2 İmmunoreaktivitesi Üzerine Etkisi

Öz

Karbon tetraklorür (CCl4) toksik etkiye sahip ksenobiyotik bir bileşiktir. CCI4, gastrointestinal sistem, solunum ve deri tarafından emilir. Yapılan çalışmalarda Ganoderma lucidumun (GL, Reishi Mantarı), CCl4 gibi hepatotoksik ajanların neden olduğu karaciğer hastalıklarına karşı, birçok ülkede binlerce yılı aşkın süredir tıbbi mantar olarak kullanılmakta olduğu ve kansere varıncaya kadar birçok hastalığa karşı direnç arttırdığı ve tedavi ettiği düşünülerek kullanıldığı bildirilmiştir. Çalışmada yetişkin dönemdeki sıçanlara karbon tetraklorür ve Ganoderma lucidum uygulaması yapılarak siklooksijenaz-2 (COX-2)’nin immunohistokimyasal lokalizasyon ve ekspresyonu incelendi. Çalışmada 8-10 haftalık 32 adet yetişkin Spraque-Dawley ırkı erkek sıçan kullanıldı. Sıçanlar; kontrol, CCI4, Ganoderma lucidum (GL), CCI4+GL olmak üzere 4 gruba ayrıldı. Deneysel uygulamalar sonucunda kontrol ve GL grubunda karaciğer dokusu normal, CCI4 grubunda ise sentral ve portal alanda multifokal nekroz alanları, hepatosellüler dejenerasyon, hücre infiltrasyonu, sinuzoidal dilatasyon ve konjesyon gözlendi. CCI4 ile birlikte GL verilen grupta ise lezyon şiddet ve yoğunluğunda azalmalar tespit edildi. COX-2 immunoreaktivitesi; sentral venadan kierman aralığına kadar olan bölgede hepatosit sitoplazmasında daha yaygın olarak saptanırken, hepatosit nükleusunda sporadik olarak tespit edildi. Kan plazma örneklerinde CCI4, Total antioksidan seviyede (TAS) azalmaya yol açarken, Total oksidan seviye (TOS), Aspartat aminotransferaz (AST) ve Alanin aminotransferaz (ALT) düzeylerinde ise artışa sebep olduğu gözlenmiştir. Alternatif ve halk tıbbında önemli yere sahip olan Ganoderma lucidum'un ise oksidatif stresi hepatoprotektif etkisi ile azalttığı, karaciğerdeki enflamatuar yanıtı inhibe ettiği görülmektedir.

Anahtar Kelimeler

The Effect of Red Reishi Mushroom (Ganoderma lucidum) Extract on Carbon Tetrachloride Induced Liver Injury and Cyclooxygenase-2 Immunoreactivity

Abstract

Carbon tetrachloride (CCl4) is a xenobiotic compound with toxicological action. It is absorbed by gastrointestinal system, respiratory system, and skin. Studies have reported that many countries have used Ganoderma lucidum (GL, Reishi Mushroom) as a medicinal mushroom against liver diseases induced by hepatotoxic agents such as CCl4 for more than thousands of years and is used for many diseases, including cancer since it has been thought that it increases resistance against them and treats them. In the present study, immunohistochemical localization and expression of cyclooxygenase-2 (COX-2) by administrating carbon tetrachloride and Ganoderma lucidum in adult rats were examined. In the study, 32 adult Spraque-Dawley male rats that were 8-10 weeks old were used. Rats were divided into 4 groups as control, CCI4, Ganoderma lucidum (GL), and CCI4+GL. As a result of the experimental applications, the liver tissue was found to be normal in the control and GL groups, and multifocal necrosis areas, hepatocellular degeneration, cell infiltration, sinusoidal dilatation, and congestion were observed in the central and portal areas in CCI4 group. In the CCI4+GL group, decreases were observed in lesion severity and density. COX-2 immunoreactivity was detected as more common in hepatocyte cytoplasm in the area from the central vena to the Kiernan space, while it was observed as sporadic in the hepatocyte nucleus. While CCI4 caused a decrease in total antioxidant level (TAS) in blood plasma samples, it caused an increase in total oxidant level (TOS), Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. It is seen that Ganoderma lucidum, which has an important place in alternative and folk medicine, reduces oxidative stress with its hepatoprotective effect and inhibits the inflammatory response in the liver.

Keywords

Supporting Institution

Gaziantep Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü

Project Number

IMYO.YLT.19.01

References

Abraham, P. & Wilfred, G. (1999). Oxidative damage to the lipids and proteins pf the lungs, testis and kidney of rats during carbon tetrachloride intoxication. Clinica Chimica Acta, 289(1-2), 177-9. https://doi.org/10.1016/s0009-8981(99)00140-0
Abdel-Daim, M.M., Taha, R., Ghazy, E.W., & El-Sayed, Y.S. (2016). Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies. Canadian Journal of Physiology and Pharmacology, 94(1), 81-8. https://doi.org/10.1139/cjpp-2015-0131
Al-Attar, A.M. (2015). Effect of grape seed oil on diazinon-induced physiological and histo-pathological alterations in rats. Saudi Journal of Biological Sciences, 22(3), 284-292. https://doi.org/ 10.1016/j.sjbs.2014.12.010
Atasever, A., Sayar, E., Ekebaş, G., Şentürk, M., & Eren, M. (2020). Ratlarda Karbon Tetraklorür ile Oluşturulan Kronik Karaciğer Hasarı Üzerine Susam Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi. Journal of Cumhuriyet University Health Sciences Institute, 5(3), 144-160.
Atasever, A. & Yaman, D. (2014). The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats. Experimental and Toxicologic Pathology, 66(8), 361-5. https://doi.org/ 10.1016/j.etp.2014.04.008
Basu, S. (2003). Carbon tetrachloride-induced lipid peroxidation: Eicosanoid formation and their regulation by antioxidant nutrients. Toxicology, 189(1-2), 113-27. https://doi.org/10.1016/s0300-483x(03)00157-4
Bernet, D., Schmidt, H., Meier, W., Brkhardt-Holm, P., & Wahli, T. (1999). Histopathology in fish: Proposal for a protocol to assess aquatic pollution. Journal of Fish Diseases, 22(1), 25-34. https://doi.org/10.1046/ j.1365-2761.1999.00134.x
Bellassoued, K., Hsouna, A. B., Athmouni, K., Pelt, J. V., & Ayadi, F. M. (2018). Protective effects of Mentha piperita L. leaf essential oil against CCl4 induced hepatic oxidative damage and renal failure in rats. Lipids in Health and Disease, 17, 1-14. https://doi.org/10.1186/s12944-017-0645-9

Cör, D., Knez, Ž., & Knez Hrnčič, M. (2018). Antitumour, antimicrobial, antioxidant and antiacetylcholinesterase effect of Ganoderma lucidum terpenoids and polysaccharides: A review. Molecules, 23(649), 1-22. https://doi.org/10.3390/ molecules23030649
Çiftçi, H., Er Çalışkan, Ç., Kar, F., Özkaya, A., & Güçlü, K. (2022). Evaluation of The Effects of Pomegranate Juice on Hepato-Nephrotoxicity in Male Rats Exposed To Aluminum. KSU J. Agric Nat, 25(2), 215-222. https://doi.org/10.18016/ ksutarimdoga.vi.896611.
Dannhardt, G. & Kiefer, W. (2001). Cyclooxygenase inhibitors-current status and future prospects. European Journal of Medicinal Chemistry, 36(2), 109-126. https://doi.org/10.1016/s0223-5234(01) 01197-7
Domitrovica, R., Jakovac, H., & Blagojevi, G. (2011). Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl4-intoxicated mice. Toxicology, 280(1-2), 33-43. https://doi.org/10.1016/j.tox.2010. 11.005
El-haskoury, R., Al-Waili, N., Kamoun, Z., Makni, M., AlWaili, H., & Lyoussia, B. (2018). Antioxidant activity and protective effect of Carob honey in CCl4-induced kidney and liver injury. Archives of Medical Research, 49(5), 306-313. https://doi.org/ 10.1016/j.arcmed.2018.09.011
Elmubarak, S. & Özsoy, N. (2016). Histoprotective effect of vitamin D against carbon tetrachloride nephrotoxicity in rats. Human & Experimental Toxicology, 35(7), 713-23. https://doi.org/10.1177/ 0960327115598387
Erel, O. (2004). A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable abts radical cation. Clinical Biochemistry, 37(4), 277-285. https://doi.org/10.1016/j.clinbiochem.2003.11.015
Erel, O. (2005). A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry, 38, 1103-1111. https://doi.org/ 10.1016/j.clinbiochem.2005.08.008 Fu, J.Y., Masferrer, J., Seibert, K., Raz, A., & Needleman, P. (1990). The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. International Journal of Biological Chemistry, 265(28), 16737-40. https://doi.org/10.1016/S0021-9258(17)44821-6
Gao, Z., Yuan, F., Li, H., Feng, Y., Zhang, Y., Zhang, C., Zhang, J., Song, Z., & Jia, L. (2019). The ameliorations of Ganoderma applanatum residue polysaccharides against CCl4 induced liver injury. International Journal of Biological Macromolecules, 137, 1130-1140. https://doi.org/ 10.1016/j.ijbiomac.2019.07.044
Ganie, S.A., Haq, E., Hamid, A., Qurishi, Y., Mahmood, Z., Zargar, B.A., Masood, A., & Zargaret, M.A. (2011). Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of Podophyllum hexandrum. BMC Complementary and Alternative Medicine, 11, 17, 1-10. https://doi.org/10.1186/1472-6882-11-17
Gambaro, G. (2002). Strategies to safely interfere with prostanoid activity while avoiding adverse renal effects: could COX‐2 and COX‐LOX dual inhibition be the answer? Nephrology Dialysis Transplantation, 17(7), 1159-62. https://doi.org/ 10.1093/ndt/17.7.1159
Hawkey, C.J. (2001). COX-1 and COX-2 inhibitors. Best Practice and Research in Clinical Gastroenterology, 15(5), 801-820. https://doi.org/ 10.1053/bega.2001.0236
Hoffmann, C. (2000). COX-2 in Brain and Spinal Cord-Implications for Therapeutic Use. Current Medicinal Chemistry, 7(11), 1113-20. https://doi. org/10.2174/0929867003374282
Jiang, W., Gao, M., Sun, S., Bi, A., Xin, Y., Han, X., Wang, L., Yin, Z., & Luo, L. (2012). Protective effect ofL-theanine on carbon tetrachloride induced acute liver injuryin mice. Biochemical and Biophysical Research Communications, 422(2), 344-350. https://doi.org/10.1016/j.bbrc.2012.05.022
Kandimalla, R., Kalita, S., Saikia, B., Choudhury, B., Singh, Y.P., Kalita, K., Dash, S., & Kotoky, J. (2016). Antioxidant and hepatoprotective potentiality of Randia dumetorum lam. leaf and bark via inhibition of oxidative stress and inflammatory cytokines. Frontiers in Pharmacology, 7, 205, 1-8. https://doi.org/10.3389/ fphar.2016.00205
Karakus, E., Karadeniz, A., Simsek, N., Can, I., Kara, A., Yildirim, S., Kalkan, Y., & Kisa, F. (2011). Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCI4). Journal of Hazardous Materials, 195, 208-213. https://doi.org/ 10.1016/j.jhazmat. 2011.08.027
Kaya Çavuşoğlu, B., Sağlık, B. N., Acar Çevik, U., Osmaniye, D., Levent, S., Özkay, Y., & Kaplancıklı, Z.A. (2021). Design, synthesis, biological evaluation and docking studies of some novel chalcones as selective COX‐2 inhibitors. Archiv der Pharmazie, 354(3), 1-9. https://doi.org/10.1002/ardp.202000273
Khalifa, F.K., Khalil, F.A., Barakat, H.A., & Hassan, M.M. (2011). Protective role of wheat germ and grape seed oils in chlorpyrifos-induced oxidative stress, biochemical and histological alterations in liver of rats. Australian Journal of Basic and Applied Sciences, 5(10), 54-66.
Kim, J.W., Kim, H.I., Kim, J.H., Kwon, O.C., Son, E.S., Lee, C.S., & Park, Y.J. Effects of Ganodermanondiol, a New Melanogenesis Inhibitor from the Medicinal Mushroom Ganoderma lucidum. International Journal of Molecular Sciences, 17(11), 1798. https://doi.org/10.3390/ijms 17111798
Kim, D.H., Shim, S.B., Kim, N.J., & Jang, I.S. (1999). β-Glucuronidaseinhibitory activity and hepatoprotective effect of Ganoderma lucidum. Biological and Pharmaceutical Bulletin, 22(2), 162-4. https://doi.org/10.1248/bpb.22.162
Koçak, Y., Oto, G., Yücel, U.M., Yaşar, S., & Arıhan, O. (2019). Karbon tetraklorür ile Oluşturulan Doku Hasarında Allium schoenoprasum L. Uygulamasının Karaciğer ve Böbrek Dokusunda Total Antioksidan ve Total Oksidan Düzeylerine Etkisi. Van Sağlık Bilimleri Dergisi, 12(3), 1-10.
Kwon, S.C. & Kim, Y.B. (2011). Antifibrotic activity a fermentation filtrate of Ganoderma lucidum. Laboratory Animal Research, 27(4), 369-371. https://doi.org/10.5625/lar.2011.27.4.369 Lida, C., Fujii, K., Koga, E., Washino, Y., Kitamura, Y., Ichi, I., & Kojo S. Effect of alpha-tocopherol on carbon tetrachloride intoxication in the rat liver. Archives of Toxicology, 83(5), 477-83. https://doi.org/10.1007/s00204-008-0394-7
Li, M.H., Feng, X., Deng Ba, D.J., Chen, C., Ruan, L. Y., Xing, Y.X., Chen, L.Y., Zhong, G.J., &Wang, J. (2019). Hepatoprotection of Herpetospermum caudigerum Wall. against CCl4-induced liver fibrosis on rats. Journal of Ethnopharmacology, 229, 1-14. https://doi.org/10.1016/j.jep.2018.09.033
Lin, W.C, & Lin, W.L. (2006). Ameliorative effect of Ganoderma lucidum on carbon tetrachloride-induced liver fibrosis in rats. World Journal of Gastroenterology, 14, 12(2), 265-270. https://doi. org/10.3748/wjg.v12.i2.265
Lin, J.M., Lin, C.C., Chen, M.F., Ujiie, T., & Takada, A. (1995). Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum. Journal of Ethnopharmacology, 47(1), 33-41. https://doi.org/ 10.1016/0378-8741(95)01251-8
Luna, L.G. (1968). Manual of histologic staining methods of armed forces institute of pathology. Blakiston Division, Graw. Hill Book Comp. 3rd edition, London. Lv, P., Luo, H.S., Zhou, X.P., Paul, S.C., Xiao, Y.J., Si, X.M., & Liu, S.Q. (2006). Thalidomide prevents rat liver cirrhosis via inhibition of oxidative stress. Pathology Research and Practice, 202(11), 777-88. https://doi.org/10.1016/j.prp.2006.08.002
Nur, G., Yıldız, S. E., Nazlı, M., & Sözmen, M. (2015). Puberte döneminde capsaicin uygulanan sıçanların karaciğerinde COX-1 ve COX-2’nin immuno-histokimyasal lokalizasyonu. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 62, 45-50. https://doi.org/10.1501/Vetfak_0000002656
Nur, G., Nazlı, M., Yıldız, S. E. (2014). Immunohistochemical localization of transforming growth factor beta-2 and gene expression using real-time PCR in capsaicin-administered rat testis during puberty.Turkish Journal of Veterinary and Animal Sciences, 38(4), 377-382. https://doi.org/ 10.3906/vet-1302-16
Ozkan, G., Kamiloglu, S., Ozdal, T., Boyacioglu, D., & Capanoglu, E. (2016). Potential use Turkish medicinal plants in the treatment of various diseases. Molecules, 21(3), 257. https://doi.org/ 10.3390/molecules21030257
Pradeep, K., Victor Raj Mohan, C., Gobianand, K., & Karthikeyan, S. (2010). Protective effect of Cassia fistula Linn. On diethylnitrosamine induced hepatocellular damage and oxidative stres in ethanol pretreated rats. Biological Research, 43(1), 113-25. http://dx.doi.org/10.4067/S0716-9760 2010000100013
Said, M.M., Azab, S.S., Saeed, N.M., & El-Demerdash, E. (2018). Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation and TGF-b/ Smad Inhibition in Rats. Annals of Hepatology, 17(2), 307-317. https://doi.org/ 10.5604/01.3001.0010.8661
Satria, D., Amen, Y., Niwa, Y., Ashour, A., Allam, A.E., Shimizu, K., & Lucidumol, D. (2019). A new lanostane-type triterpene from fruiting bodies of Reishi (Ganoderma lingzhi). Natural Product Research, 33(2), 189-195. https://doi.org/ 10.1080/14786419.2018.1440229
Seidal, T., Balaton, A.J., & Battifora, H. (2001). Interpretation and quantification of immunostains. American Journal of Surgical Pathology, 2589, 1204-1207. https://doi.org/10.1097/00000478-200109000-00013
Shahjahan, M., Sabitha, K.E., Jainu, M., Shyamala Devi., C. S. (2004). Effect of Solanum trilobatum against carbon tetrachloride induced hepatic damage in albino rats. Indian Journal of Medical Research, 120, 194-8.
Shieh, Y.H., Liu, C.F., Huang, Y.K., Yang, J.Y., Wu, I.L., Lin, C.H., & Lin, S.C. (2001). Evaluation of the hepatic and renal protective effects of Ganoderma lucidum in mice. American Journal of Chinese Medicine, 29, 501-7. https://doi.org/10.1142/ S0192415X01000526
Shu, S., Ju, G., & Fan, L. (1988). The glucose oxidase-dabnickel in peroxidase histochemistry of the nervous system. Neuroscience Letters, 85, 169-171. https://doi.org/10.1016/0304-3940(88)90346-1 Sliva, D., Loganathan, J., Jiang, J., Jedinak, A., Lamb, J.G., Terry, C., Baldridge, L.A., Adamec, J., Sandusky, G.E., & Dudhgaonkar, S. (2012). Mushroom Ganoderma lucidum Prevents Colitis-Associated Carcinogenesis in Mice. PLOS ONE, 7(10), 1-13. https://doi.org/10.1371/journal.pone. 0047873
Smith, W.L., Garavito, R.M., & DeWitt, D.L. (1996). Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and-2. Journal of Biological Chemistry, 271(52), 33157-60. https://doi.org/ 10.1074/jbc.271.52.33157
Stickel, F., Brinkhaus, B., Krahmer, N., Seitz, H.K., Hahn, E.G., & Schuppan, D. (2002). Antifibrotic properties of botanicals in chronic liver disease. Hepatogastroenterology, 49(46), 1102-1108.
Tekeli, H. & Bildik, A. (2013). Karbon tetraklorür ile oluşturulan karaciğer hasarında Glutatyon (GSH) ve glutatyon s-transferaz (GST) aktivitesi üzerine N-asetil sisteinin etkisi. Balıkesir Sağlık Bilimleri Dergisi, 5(2), 83-7.
Verma, P.K., Raina, R., Sultana, M., & Singh, M. (2015). Modulatory Effects of Alstonia scholaris on biochemical and antioxidant parameters in experimentally induced hepatotoxicity in wistar rats. Research Journal of Medicinal Plants, 4, 406-16. https://doi.org/10.3923/rjmp.2015.406.416
Yıldız, S.E., Nur, G., Nazlı, M., & Sözmen, M. (2013). Immunohistochemical distribution of COX-1 and COX-2 in the renal tissue of pubere rats treated with capsaicin. Revue de Medecine Veterinaire, 164(8-9), 389-394.
Zhang, G.L., Wang, Y.H., Ni, W., Teng, H.L., & Lin, Z.B. (2002). Hepatoprotective role of Ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice. World Journal of Gastroenterology 8(4), 728-733. https://doi.org/ 10.3748/wjg.v8.i4.728
Zhao, Q., Peng, Y., Huang, K., Lei, Y., Liu, H.L., Tao, Y.Y., & Liu, C.H. (2016). Salvianolate protects hepatocytes from oxidative stress by attenuating mitochondrial injury. Evidence-Based Complementary and Alternative Medicine, 2016, 5408705, 1-10. https://doi.org/10.1155/ 2016/ 5408705
Zhao, X. (2013). Hawk tea (Litsea coreana Levl. Var. lanuginose) attenuates CCl4 induced hepatic damage in Sprague Dawley rats. Experimental and Therapeutic Medicine, 5(2), 555-560. https://doi.org/10.3892/etm.2012.840
Zhu, Q.Y. (1989). Analysis of blood vessel invasion by cells of thyroid follicular carcinoma using image processing combined with immunohistochemistry. Zhonghua Yi Xue Za Zhi, 69, 573-575.

Details

Primary Language

English

Subjects

Structural Biology

Journal Section

Research Article

Authors

Halime Yavuz
0000-0003-1676-2862
Türkiye

Gökhan Nur ^*
0000-0002-5861-8538
Türkiye

H. Ahmet Deveci
0000-0002-3862-1991
Türkiye

İzzettin Güler
0000-0001-6682-7156
Türkiye

Early Pub Date

October 13, 2023

Publication Date

February 28, 2024

Submission Date

October 30, 2022

Acceptance Date

June 15, 2023

Published in Issue

Year 1970 Volume: 27 Number: 1

DOI

https://doi.org/10.18016/ksutarimdoga.vi.1196713

IZ

https://izlik.org/JA79MH59BS

Cite

RIS / Bibtex

APA

Yavuz, H., Nur, G., Deveci, H. A., & Güler, İ. (2024). The Effect of Red Reishi Mushroom (Ganoderma lucidum) Extract on Carbon Tetrachloride Induced Liver Injury and Cyclooxygenase-2 Immunoreactivity. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 27(1), 1-13. https://doi.org/10.18016/ksutarimdoga.vi.1196713