Biochemical, hematological, peripheral smear and weight evaluation of low dose Epigallocatechin Gallate in Diethylnitrosamine administered rats
Yıl 2023,
, 365 - 370, 22.03.2023
Murat Çetin Rağbetli
,
Zübeyt Bilici
,
Okan Arıhan
,
Cennet Ragbetli
,
Hadi Geylan
Öz
Background: Currently, with the development of technology, the use of many chemicals especially Diethylnitrosamine (DEN) in agriculture and industry has increased. The polyphenolic compounds of Epigallocatechin gallate (EGCG) is the active ingredient of green tea. It has been reported that green tea has antioxidant effects. In this study, effects of low dose Epigallocatechin gallate (EGCG), against exposure of Diethylnitrosamine administered rats.
Methods: As a group, groups were divided into five groups of ten rats for the application as Control, Sham, DEN EGCG and DEN+EGCG. The parameters analyzed are hemogram, biochemical, peripheral smear and weight.
Results: DEN injection has significantly increased LDH, AST, ALT and ALP values, Which are signs of hepatocyte injuries. The number of WBCs increased in the EGCG group. In terms of HDL and TChol levels, the group in which DEN+EGCG were applied together was found to be the highest and TG and LDL levels were found to be lowest. The current study will be a comprehensive study demonstrating the effects of low-dose EGCG against DEN-administred rats.
Destekleyen Kurum
Van Yüzüncü Yil University Scientific Research Administration
Proje Numarası
Project number: 2017 TYL 6343
Teşekkür
This master thesis was supported Van Yüzüncü Yil University Scientific Research Administration
Kaynakça
- 1-Owumi SE, Dim UJ, Najophe ES. Diethylnitrosamine aggravates cadmium-induced hepatorenal oxidative damage in prepubertal rats. Toxicol Ind Health. 2019;35:537-547.
- 2-Gayathri R, Priya DKD, Gunassekaran, GR, Sakthisekaran D. Ursolic acid attenuates oxidative stress-mediated hepatocellular carcinoma Induction by diethylnitrosamine in male wistar rats. Asian Pacific J Cancer Prev. 2009;10:933-8.
- 3-Horng C, Huang C, Yang M, Chen, T, Chang Y. Nelumbo nucifera leaf extract treatment attenuated preneoplastic lesions and oxidative stress in the livers of diethylnitrosamine-treated rats. Environ Toxicol. 2017;32:2327-2340.
- 4-Jagdale SG, Arulmozhi S, Jamadagni S, Mahadik KR. Pharmacological effect of Diosgenin on Diethylnitrosamine induced hepatotoxicıiy in Wistar Rats. International Journal of Pharmaceutıial Sciences and Research. 2019;11:3797-05.
- 5-Thirynavukkarasu C, Sakthisekaran D. Stabilization of membrane bound enzyme profiles by sodium selenite in N-nitrosodiethylamine induced and phenobarbital promoted hepatocarcinogenesis in rats. Biomedicine Pharm acotherapy. 2003;57:117-23.
- 6-Ma XD, Ma X, Sui Y, Wan WL, Wang C. Signal transduction of gap junctional genes, connexin 32, connexin 43 in human hepatocarcinogenesis. World J Gastroenterol. 2003;9:946-50.
- 7-Kang JS, Wanibuchi H, Morimura K. Role of CYP2E1 in Diethylnitrosamine-Induced hepatocarcinogenesis in vivo. Cancer Res. 2007;67:11141-6.
- 8-Henning M, Fajardo-Lir C, Lee HW, Youssefian AA, Go VLW, Heber D. Catechin content of 18 teas and a green tea extract supplement correlates with antioxidant capasity. Nutrition and Cancer. 2009;45:226- 35.
- 9-Cooper R, Morré DJ, Morré DM. Medical benefits of green tea: part I. review of non-cancer health benefits. The Journal of Alternative and Complementary Medicine. 2005;11:521-8.
- 10-Weisburger JH, Chung FL. Mechanism by chronic disease caused by nutritional factors and tobacco products and their prevention by tea polyphenols. Food and Chemical Toxicology. 2002;40:145-54.
11-Liu Z, Wild C, Ding Y, Ye N, Chen H, Wold EA, Zhou J. BH4 domain of Bcl-2 as a novel target for cancer therapy. Drug Discov Today. 2016;21:989–996.
- 12-Akay C. Biyomarkerlerin toksikolojide kullanımı, Gülhane Tıp Derg. 2004;46:73-83.
- 13- Kısacam MA, Kocamuftuoglu GO, Tektemur NK, Ozan ST. The evaluation of the therapeutic potential of hesperetin on diethylnitrosamine and phenobarbital induced liver injury in rats. Ankara Univ Vet Fak Derg. 2022;69:149-156.
- 14-Tran PL, Kim SA, Choi HS, Yoon JH, Ahn SG. Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo. BMC Cancer 2010;10:276-83.
- 15-Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001 Jun;85(6):958-65.
- 16-Amin HAM, Altındağ F, Colcimen N, Rağbetli MC. The effects thymoquinone on in diethylnitrosamine induced hepatic injury in rats: A sterelogical study. International Journal of Current Research. 2017;12:62986-62989.
- 17-Wang Q, Zhang J, Li Y, Shi H, Wang H, Chen B, Wang F, Wang Z, Yang Z, Wang L. Green tea polyphenol epigallocatechin-3-gallate increases atherosclerotic plaque stability in apolipoprotein E-deficient mice fed a high-fat diet. Kardiol Pol. 2018;76:1263-70.
- 18-Nauseef WM, Borregaard N. Neutrophils at work. Nat Immunol. 2014;15:02–611.
- 19-Arslan O, Erzengın M, Sınan S, Özensoy O. Purification of Mulberry (Morus alba l.) Polyphenol Oxidase by Affinity Chromatography and Investigation of Its Kinetic and Electrophoretic Properties. Food Chemistry. 2004;88:479–484.
- 20-Suliburska J, Bogdanski P, Szulinska M, Stepien M, Upek-Musialik D, Jablecka A. Effects of green tea supplementation on elements, total antioxidants, lipids, and glucose values in the serum of obese patients. Biol Trace Elem Res. 2012;149:315–22.
- 21-Gubur S. Basit karbonhidrat içeriği yüksek diyetle beslenen sıçanlarda yeşil çayın antioksidan etkisinin incelenmesi Doktora tezi. Ankara: Başkent Üniversitesi Sağlık Bilimleri Enstitüsü Beslenme ve Diyetetik Anabilim Dalı. 2015;412617.
- 22-Vinson JA, Teufel K, Wu N. Green and Black Teas Inhibit Atheroscleros is by Lipid, Antioxidant and Fibrinolytic Mechanisms. Journal of Agricultural and Food Chemistry. 2004;52:3661-3665.
- 23-Yang CS, Wang X, Lu G, Picinich SC. Nat Rev Cancer. 2009;9:429–439.
- 24-Jahan MS, Vani G, Shyamaladevi CS. Effect of Solanum trilobatum on hepatic drug metabolising enzymes during diethylnitrosamine-induced hepatocarcinogenesis promoted by Phenobarbital in rat. Hepatol Res. 2007;37:35-49.
- 25-Rezaie A, Fazlara A, Karamolah MH, Eidizadeh H, Pashmforosh M. Effects of Echinacea purpurea on hepatic and renal toxicity induced by diethylnitrosamine in rats. Jundishapur J Nat Pharm Prod. 2013;8:60-64.
- 26-Merhan O, Özcan A, Atakişi E, Öğün MÖ, Kükürt A. The Effect of β-carotene on Acute Phase Response in Diethylnitrosamine Given Rabbits. Kafkas Univ Vet Fak Derg. 2016;22:533-537.
- 27-Boege Y, Malehmir M, Healy M.E, Bettermann K, Lorentzen A et al. A dual role of caspase-8 in triggering and sensing proliferation-associated DNA damage, a key determinant of liver cancer development. Cancer Cell. 2017;32:342–359.
- 28-Tang Y, Cao J, Cai Z, An H, Li Y, Peng Y, Chen N, Luo A, Tao H, Li K. Epigallocatechin gallate induces chemopreventive effects on rats with diethylnitrosamine‑induced liver cancer via inhibition of cell division cycle 25A. Mol Med Rep. 2020;22:3873-3885.
- 29-Almatroodi SA, Alsahli MA, Alharbi HM, Khan AA, Rahmani AH. Epigallocatechin-3-Gallate (EGCG), An Active Constituent of Green Tea: Implications in the Prevention of Liver Injury Induced by Diethylnitrosamine (DEN) in Rats. Appl Sci. 2019;4821:1-16.
- 30-Ge RL, Witkowski S, Zhang Y, Alfrey C, Sivieri M, Karlsen T, Resaland GK, Harber M, Stray-Gundersen J, Levine BD. Determinants of erythropoietin release in response to short-term hypobaric hypoxia. J Appl Physiol. 2002;92(6):2361-7.
- 31-Mostafa-Hedeab M, Hassan ME, Halawa TF, ِWani FA. Epigallocatechin gallate ameliorates tetrahydrochloride-induced liver toxicity in rats via inhibition of TGFβ / p-ERK/p-Smad1/2 signaling, antioxidant, anti-inflammatory activity. Saudi Pharmaceutical Journal. 2022; 27 June 2022.
- 32-Nikoo M, Regenstein JM, Gavlighi HA. Antioxidant and antimicrobial activities of (-)-epigallocatechin-3-gallate (EGCG) and its potential to preserve the quality and safety of food. Comp Reviews Food Sci Food Safety. 2018;17:732-753.
- 33-Zhu J, Jiang Y, Yang X, Wang S, Xie C, Li X, Li Y, Chen Y, Wang X, Meng Y, Zhu M, Wu R, Huang C, Ma X, Geng S, Wu J, Zhong C. Wnt/β-Catenin pathway mediates (-)-epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells. Biochem Biophys Res Commun. 2017;482:15-21.
Dietilnitrozamin uygulanan sıçanlarda düşük doz Epigallocatechin Gallate'nin biyokimyasal, hematolojik, periferik yayma ve ağırlık değerlendirilmesi
Yıl 2023,
, 365 - 370, 22.03.2023
Murat Çetin Rağbetli
,
Zübeyt Bilici
,
Okan Arıhan
,
Cennet Ragbetli
,
Hadi Geylan
Öz
Arka plan: Günümüzde teknolojinin gelişmesiyle birlikte başta Dietilnitrozamin (DEN) olmak üzere birçok kimyasalın tarım ve sanayide kullanımı artmıştır. Epigallocatechin gallate'nin (EGCG) polifenolik bileşikleri, yeşil çayın aktif bileşenidir. Yeşil çayın antioksidan etkileri olduğu bildirilmiştir. Bu çalışmada, düşük doz Epigallocatechin gallate (EGCG)'nin Dietilnitrozamin uygulanan sıçanlara maruz kalmaya karşı etkileri incelenmiştir.
Yöntemler: Gruplar uygulama için Kontrol, Sham, DEN EGCG ve DEN+EGCG olmak üzere on rattan oluşan beş gruba ayrıldı. Analiz edilen parametreler hemogram, biyokimyasal, periferik yayma ve ağırlıktır.
Bulgular: DEN enjeksiyonu, hepatosit yaralanmalarının belirtileri olan LDH, AST, ALT ve ALP değerlerini önemli ölçüde artırdı. EGCG grubunda WBC sayısı arttı. HDL ve TChol düzeyleri açısından DEN+EGCG'nin birlikte uygulandığı grup en yüksek, TG ve LDL düzeyleri ise en düşük bulundu. Mevcut çalışma, düşük doz EGCG'nin DEN uygulanan sıçanlara karşı etkilerini gösteren kapsamlı bir çalışma olacaktır.
Proje Numarası
Project number: 2017 TYL 6343
Kaynakça
- 1-Owumi SE, Dim UJ, Najophe ES. Diethylnitrosamine aggravates cadmium-induced hepatorenal oxidative damage in prepubertal rats. Toxicol Ind Health. 2019;35:537-547.
- 2-Gayathri R, Priya DKD, Gunassekaran, GR, Sakthisekaran D. Ursolic acid attenuates oxidative stress-mediated hepatocellular carcinoma Induction by diethylnitrosamine in male wistar rats. Asian Pacific J Cancer Prev. 2009;10:933-8.
- 3-Horng C, Huang C, Yang M, Chen, T, Chang Y. Nelumbo nucifera leaf extract treatment attenuated preneoplastic lesions and oxidative stress in the livers of diethylnitrosamine-treated rats. Environ Toxicol. 2017;32:2327-2340.
- 4-Jagdale SG, Arulmozhi S, Jamadagni S, Mahadik KR. Pharmacological effect of Diosgenin on Diethylnitrosamine induced hepatotoxicıiy in Wistar Rats. International Journal of Pharmaceutıial Sciences and Research. 2019;11:3797-05.
- 5-Thirynavukkarasu C, Sakthisekaran D. Stabilization of membrane bound enzyme profiles by sodium selenite in N-nitrosodiethylamine induced and phenobarbital promoted hepatocarcinogenesis in rats. Biomedicine Pharm acotherapy. 2003;57:117-23.
- 6-Ma XD, Ma X, Sui Y, Wan WL, Wang C. Signal transduction of gap junctional genes, connexin 32, connexin 43 in human hepatocarcinogenesis. World J Gastroenterol. 2003;9:946-50.
- 7-Kang JS, Wanibuchi H, Morimura K. Role of CYP2E1 in Diethylnitrosamine-Induced hepatocarcinogenesis in vivo. Cancer Res. 2007;67:11141-6.
- 8-Henning M, Fajardo-Lir C, Lee HW, Youssefian AA, Go VLW, Heber D. Catechin content of 18 teas and a green tea extract supplement correlates with antioxidant capasity. Nutrition and Cancer. 2009;45:226- 35.
- 9-Cooper R, Morré DJ, Morré DM. Medical benefits of green tea: part I. review of non-cancer health benefits. The Journal of Alternative and Complementary Medicine. 2005;11:521-8.
- 10-Weisburger JH, Chung FL. Mechanism by chronic disease caused by nutritional factors and tobacco products and their prevention by tea polyphenols. Food and Chemical Toxicology. 2002;40:145-54.
11-Liu Z, Wild C, Ding Y, Ye N, Chen H, Wold EA, Zhou J. BH4 domain of Bcl-2 as a novel target for cancer therapy. Drug Discov Today. 2016;21:989–996.
- 12-Akay C. Biyomarkerlerin toksikolojide kullanımı, Gülhane Tıp Derg. 2004;46:73-83.
- 13- Kısacam MA, Kocamuftuoglu GO, Tektemur NK, Ozan ST. The evaluation of the therapeutic potential of hesperetin on diethylnitrosamine and phenobarbital induced liver injury in rats. Ankara Univ Vet Fak Derg. 2022;69:149-156.
- 14-Tran PL, Kim SA, Choi HS, Yoon JH, Ahn SG. Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo. BMC Cancer 2010;10:276-83.
- 15-Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001 Jun;85(6):958-65.
- 16-Amin HAM, Altındağ F, Colcimen N, Rağbetli MC. The effects thymoquinone on in diethylnitrosamine induced hepatic injury in rats: A sterelogical study. International Journal of Current Research. 2017;12:62986-62989.
- 17-Wang Q, Zhang J, Li Y, Shi H, Wang H, Chen B, Wang F, Wang Z, Yang Z, Wang L. Green tea polyphenol epigallocatechin-3-gallate increases atherosclerotic plaque stability in apolipoprotein E-deficient mice fed a high-fat diet. Kardiol Pol. 2018;76:1263-70.
- 18-Nauseef WM, Borregaard N. Neutrophils at work. Nat Immunol. 2014;15:02–611.
- 19-Arslan O, Erzengın M, Sınan S, Özensoy O. Purification of Mulberry (Morus alba l.) Polyphenol Oxidase by Affinity Chromatography and Investigation of Its Kinetic and Electrophoretic Properties. Food Chemistry. 2004;88:479–484.
- 20-Suliburska J, Bogdanski P, Szulinska M, Stepien M, Upek-Musialik D, Jablecka A. Effects of green tea supplementation on elements, total antioxidants, lipids, and glucose values in the serum of obese patients. Biol Trace Elem Res. 2012;149:315–22.
- 21-Gubur S. Basit karbonhidrat içeriği yüksek diyetle beslenen sıçanlarda yeşil çayın antioksidan etkisinin incelenmesi Doktora tezi. Ankara: Başkent Üniversitesi Sağlık Bilimleri Enstitüsü Beslenme ve Diyetetik Anabilim Dalı. 2015;412617.
- 22-Vinson JA, Teufel K, Wu N. Green and Black Teas Inhibit Atheroscleros is by Lipid, Antioxidant and Fibrinolytic Mechanisms. Journal of Agricultural and Food Chemistry. 2004;52:3661-3665.
- 23-Yang CS, Wang X, Lu G, Picinich SC. Nat Rev Cancer. 2009;9:429–439.
- 24-Jahan MS, Vani G, Shyamaladevi CS. Effect of Solanum trilobatum on hepatic drug metabolising enzymes during diethylnitrosamine-induced hepatocarcinogenesis promoted by Phenobarbital in rat. Hepatol Res. 2007;37:35-49.
- 25-Rezaie A, Fazlara A, Karamolah MH, Eidizadeh H, Pashmforosh M. Effects of Echinacea purpurea on hepatic and renal toxicity induced by diethylnitrosamine in rats. Jundishapur J Nat Pharm Prod. 2013;8:60-64.
- 26-Merhan O, Özcan A, Atakişi E, Öğün MÖ, Kükürt A. The Effect of β-carotene on Acute Phase Response in Diethylnitrosamine Given Rabbits. Kafkas Univ Vet Fak Derg. 2016;22:533-537.
- 27-Boege Y, Malehmir M, Healy M.E, Bettermann K, Lorentzen A et al. A dual role of caspase-8 in triggering and sensing proliferation-associated DNA damage, a key determinant of liver cancer development. Cancer Cell. 2017;32:342–359.
- 28-Tang Y, Cao J, Cai Z, An H, Li Y, Peng Y, Chen N, Luo A, Tao H, Li K. Epigallocatechin gallate induces chemopreventive effects on rats with diethylnitrosamine‑induced liver cancer via inhibition of cell division cycle 25A. Mol Med Rep. 2020;22:3873-3885.
- 29-Almatroodi SA, Alsahli MA, Alharbi HM, Khan AA, Rahmani AH. Epigallocatechin-3-Gallate (EGCG), An Active Constituent of Green Tea: Implications in the Prevention of Liver Injury Induced by Diethylnitrosamine (DEN) in Rats. Appl Sci. 2019;4821:1-16.
- 30-Ge RL, Witkowski S, Zhang Y, Alfrey C, Sivieri M, Karlsen T, Resaland GK, Harber M, Stray-Gundersen J, Levine BD. Determinants of erythropoietin release in response to short-term hypobaric hypoxia. J Appl Physiol. 2002;92(6):2361-7.
- 31-Mostafa-Hedeab M, Hassan ME, Halawa TF, ِWani FA. Epigallocatechin gallate ameliorates tetrahydrochloride-induced liver toxicity in rats via inhibition of TGFβ / p-ERK/p-Smad1/2 signaling, antioxidant, anti-inflammatory activity. Saudi Pharmaceutical Journal. 2022; 27 June 2022.
- 32-Nikoo M, Regenstein JM, Gavlighi HA. Antioxidant and antimicrobial activities of (-)-epigallocatechin-3-gallate (EGCG) and its potential to preserve the quality and safety of food. Comp Reviews Food Sci Food Safety. 2018;17:732-753.
- 33-Zhu J, Jiang Y, Yang X, Wang S, Xie C, Li X, Li Y, Chen Y, Wang X, Meng Y, Zhu M, Wu R, Huang C, Ma X, Geng S, Wu J, Zhong C. Wnt/β-Catenin pathway mediates (-)-epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells. Biochem Biophys Res Commun. 2017;482:15-21.