Mustafa Bahadır KAYMAZ, FATİH MEHMET KANDEMİR, ESRA PAMUKÇU, YESARİ ERÖKSÜZ, NECMİ ÖZDEMİR

Effects of Aqueous Artichoke (Cynara scolymus) Leaf Extract on Hepatic Damage Generated by Alpha-Amanitine

Dünyada mantar zehirlenmelerine bağlı ölümlerin yaklaşık 90%'ına Amanita phalloides türü mantarlar neden olmaktadır. Alfa-amanitin, bisiklik oktapeptid yapıda bu zehirlenmelerden sorumlu ana yapıdır. Bu çalışmada, enginar sulu yaprak ekstresinin oluşturulan toksisite üzerine etkilerinin araştırılması amaçlanmıştır. Çalışmada, Sprague-Dawley cinsi 28 erkek rat rastgele 4 gruba ayrıldı. Gruplar, kontrol grubu (serum fizyolojik 0.1 mL ip), alfa-amanitin (3 mg/kg tek doz ip), enginar yaprak ekstresi (oral 1.5 g/kg, 14 gün) ve tedavi uygulanan (alfaamanitin 3 mg/kg tek doz ip+ enginar yaprak ekstresi oral 1.5 g/kg, 14 gün) olmak üzere belirlendi. Alfa-amanitinin karaciğer malondialdehit (MDA) düzeyini arttırdığı, süperoksit dismutaz (SOD), glutatyon peroksidaz (GSH-Px), katalaz (CAT) aktiviteleri ile glutatyon (GSH) düzeyini düşürdüğü tespit edilmiştir. Enginar sulu yaprak ekstresi takviyesinin MDA seviyesini düşürürken antioksidan parametrelerde ve histopatolojik bulgularda iyileşmeye neden olduğu saptanmıştır. Çalışma sonucunda, alfa-amanitin kaynaklı karaciğer hasarına karşı enginarın sulu ekstresinin kullanımının, tedaviye destek olarak kullanılabileceği düşünülmektedir.

Alfa-Amanitin İle Oluşturulmuş Karaciğer Hasari Üzerine Enginar (Cynara scolymus) Sulu Yaprak Ekstresinin Etkileri

Approximately 90% of mushroom poisoning deaths in the world is caused by types of Amanita phalloides. Alpha-amanitine has a bicyclic octapeptide structure, which is the main structure responsible for these poisoning cases. In the present study, it was aimed to investigate effects of leaf extracts with artichoke extract on this toxicity. In the study, 28 male rats of Sprague-Dawley species were randomized to 4 groups. The groups were designed as control; receiving serum physiological solution of 0.1 mL intraperitoneally (ip), alpha-amanitine; receiving 3 mg/kg single dose ip, artichoke leaf extract; receiving 1.5 g/kg orally for 14 d, and treatment group¸ receiving alpha-amanitine 3 mg/kg single dose ip+artichoke leaf extract 1.5 g/kg orally for 14 d. It was determined that alpha-amanitine increased hepatic malondialdehyde (MDA) levels, and decrease superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities with decreasing glutathione (GSH) levels. The supplementation with extract with artichoke, decreased MDA levels, it improved antioxidant parameters, and histopathological findings, so it was decided that extract with artichoke juice might be beneficial in alpha-amanitine related hepatic damage.

PDF

___

1. Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, Nelson LS: Mushrooms. In, Goldfrank LR (Ed): Goldfrank's ToxicologicEmergencies. 8th edn., 1564-1569, Mc Graw-Hill Company, New York, 2006.
2. Vural N: Doğal Kaynaklı Zehirler. In, Vural N (Ed): Toksikoloji. 73th edn.,610-623, Ankara Üniv Ecz Fak Yayınları, Ankara, 1996.
3. Klein AS, Hart J, Brems JJ, Goldstein L, Lewin K, Busuttil RW: Amanita poisoning treatment and the role of liver transplantation. Am J Med, 86, 187-193, 1989. DOI: 10.1016/0002-9343(89)90267-2
4. Himmelmann A, Mang G, Schnorf-Huber S: Lethal ingestion of stored Amanita phalloides mushrooms. Swiss Med Wkly, 131, 616-617, 2001.
5. Nguyen VT, Giannoni F, Dubois MF, Seo SJ, Vigneron M, Kédinger C, Bensaude O: In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin. Nucleic Acids Res, 24, 2924-2929, 1996. DOI: 10.1093/nar/24.15.2924
6. Goldfrank LR, Flamenbaum NE, Lewin NA, Weisman RS, Hawland MA, Hoffman RS: Mushrooms: Toxic and hallusinogenic. In, Goldfrank LR (Ed): Goldfrank's Toxicologic Emergencies. 6th edn., 1207-1220, Mc GrawHill Company, New York, 1998.
7. Garcia J, Costa VM, Carvalho A, Baptista P, Pinho PG, Bastos ML, Carvalho F: Amanita phalloides poisoning: Mechanisms of toxicity and treatment. Food Chem Toxicol, 86, 41-55, 2015. DOI: 10.1016/j. fct.2015.09.008
8. Llorach R, Espin JC, Tomas-Barberan FA, Ferreres F: Artichoke (Cynara scolymus L.) byproducts as a potential source of healthpromoting antioxidant phenolics. J Agr Food Chem, 50, 3458-3464, 2002. DOI: 10.1021/jf0200570
9. Aktay G, Deliorman D, Ergun E, Ergun F, Yesilada E, Cevik C: Hepatoprotective effects of Turkish folk remedies on experimental liver injury. J Ethnopharmacol, 73, 121-129, 2000. DOI: 10.1016/S0378-8741(00)00286-5
10. Speroni E, Cervellati R, Govoni P, Guizzardi S, Renzulli C, Guerra MC: Efficiency of different Cynara scolymus preparations liver complaints. J Ethnopharmacol, 86, 203- 211, 2003. DOI: 10.1016/S0378-8741(03)00076-X
11. Tanker M, Tanker N: Flavonozitler. In, Tanker M, Tanker N (Eds): Farmakognozi. 218-219, Ankara Üniversitesi Basımevi, Ankara, 1991.
12. Bergö M, Wu G, Ruge T, Olivecrona T: Down-regulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on. J Biol Chem, 277, 11927-11932, 2002.DOI: 10.1074/jbc.M200325200
13. Wieland T, Faulstich H: Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous Amanita mushrooms. CRC Crit Rev Biochem, 5, 185-260, 1978. DOI: 10.3109/ 10409237809149870
14. Mehmetcik G, Ozdemirler G, Toker NK, Cevikbas U, Uysal M: Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress. Ex Toxicol Pathol, 60, 475-480, 2008. DOI:10.1016/j.etp.2008.04.014
15. Placer ZA, Cushman L, Johnson BC: Estimation of products of lipid peroxidation (malonyl dialdeyhde) in biological fluids. Anal Biochem, 16, 359-364, 1966. DOI: 10.1016/0003-2697(66)90167-9
16. Sun Y, Oberley WL, Li Y: A simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497-500, 1988.
17. Aebi H: Catalase in vitro. Methods Enzymol, 105, 121-126, 1984. DOI:10.1016/S0076-6879(84)05016-3
18. Matkovics B, Szabo L, Varga LS: Determination on enzyme activities in lipid peroxidation and glutathione pathways. Laboral Diagn, 15, 248- 249, 1988.
19. Sedlak J, Lindsay RH: Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem, 25, 192-205, 1968. DOI: 10.1016/0003-2697(68)90092-4
20. Ferguson GA, Takane Y: Repeated Measurements and Other Designs. In, Ferguson GA, Takane Y (Eds): Statistical Analysis in Psychology and Education. 6th edn., 347-390, McGraw-Hill Ryerson Ltd, Montreal, 2005.
21. Enjalbert F, Rapior S, Soulé JN, Guillon S, Amouroux N, Cabot C: Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicon, 40, 715-757, 2002. DOI: 10.1081/CLT-120014646
22. Edwards SE, Heinrich M, Rocha I, Williamson ME: Artichoke. In, Edwards SE (Ed): Phytopharmacy: An evidence-based Guide to Herbal Products. 29-31, John Wiley&Sons Ltd, Oxford, 2015.
23. Ben-Hod G, Basnizki Y, Zohary D, Mayer AM: Cynarin and chlorogenic acid content in germinanting seeds of globe artichoke (Cynara scolymus L.). J Genet Breed, 46, 63-67, 1992.
24. Gezer C, Yücecan S, Rattanc SIS: Artichoke compound cynarin differentially affects the survival, growth, and stressresponse of normal, immortalized, and cancerous human cells. Turk J Biol, 39, 299-305, 2015. DOI: 10.3906/biy-1407-67
25. Adzet T, Camarasa J, Carlos Laguna J: Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes. J Nat Prod, 50, 612-617, 1987. DOI: 10.1021/ np50052a004
26. Majeed MF, Numan IT, Noori M: Study the anti-inflammatory activity of artichoke (cynara scolymus) different extracts in experimentel models of acute inflammation in rats. Pharmacie Globale (IJCP), 6, 4-5, 2015.
27. Colak E, Ustuner MC, Tekin N, Colak E, Burukoglu D, Degirmenci I, Gunes HV: The hepatocurative effects of Cynara scolymus L. leaf extract on carbon tetrachloride-induced oxidative stress and hepatic injury in rats. Springerplus, 5, 216, 2016. DOI: 10.1186/s40064-016-1894-1
28. Escrig AJ, Dragsted LO, Daneshvar B, Pulido R, Saura-Calixto F: In vitro antioxidant activities of edible artichoke (Cynara scolymus L.) and effect on biomarkers of antioxidants in rats. J Agric Food Chem, 51, 5540-5545, 2003. DOI: 10.1021/jf030047e
29. Küçükgergin C, Aydın AF, Özdemirler-Erata G, Mehmetcik G, Toker NK, Uysal M: Effect of artichoke leaf extract on hepatic and cardiac oxidative stress in rats. Fed on high cholesterol diet. Biol Trace Elem Res, 135,264-274, 2010. DOI: 10.1007/s12011-009-8484-9