RATLARDA KARBON TETRAKLORUR İLE OLUŞTURULAN KRONİK KARACİĞER HASARI ÜZERİNE ZERDEÇAL(CURCUMA LONGA) VE MERYEMANA DİKENİNİN (SILYBUM MARIANUM) ETKİSİ

Year 2017, Volume: 26 Issue: 3, 240 - 248, 01.12.2017

Ayhan Atasever Oktay Baran Görkem Ekebaş

Abstract

Çalışmada karbon tetraklorür (CCl4) ile ratlarda oluşturulan karaciğer hasarına karşı zerdeçal ve meryemana dikeninin lipid
peroksidasyonu ve bazı biyokimyasal parametreler üzerine koruyucu etkinliği amaçlandı.
Çalışmada Wistar albino 4 aylık, 60 adet ortalama 250 gr’lık rat
kullanıldı. Kontrol grubuna tedavi uygulaması üç grup altında yapıldı. Birinci gruba haftada iki kere mısır yağı, V. gruba 100 mg/kg
meryemana dikeni, VI. gruba 80 mg/kg zerdeçal 12 hafta her gün
gavajla verildi. Deney grubuna haftada 2 kez 0,5 ml/kg CCl4
intraperitoneal enjekte edildi. Tedavi gruplarında, tedavi 12 hafta,
iki grup altında yapıldı. CCl4+meryemana dikeni ve CCl4+zerdeçal
grublarında sırasıyla CCl4 enjeksiyonuyla eş zamanlı 100 mg/kg
meryemana dikeni ve 80 mg/kg zerdeçal gavaj ile verildi. Deney
sonunda karaciğerlerin histopatolojisi ve serum biyokimyasal
parametreleri incelendi. Kontrol gruplarında karaciğerler normal
doku yapısında gözlenirken, CCl4 verilen Grup II’de hepatositlerde
dejenerasyon ve yağlanma, remark kordonlarında bozulma, portal
bölgede çoğunluğunu lenfosit mononüklear hücre infiltrasyonları,
özellikle portal bölgede belirgin, parankime yayılmış bağ dokusu
artışıyla ilgili pseudolobulasyon gözlendi. CCl4+meryemana dikeni
ve CCl4+zerdeçal gruplarında Grup II’de kine benzer karaciğer
lezyonlarına rastlanıldı. Kontrol, meryemana dikeni ve zerdeçal
gruplarına göre, CCl4 uygulanan Grup II, III ve IV serum alanin
aminotransferaz (ALT), Aspartat aminotransferaz (AST), düşük
dansiteli lipoprotein (LDL), karaciğer malondialdehit (MDA) ve
nitrik oksit (NO) değerlerinde artış; yüksek dansiteli lipoprotein
(HDL) ve albümin değerlerinde düşüş görüldü. CCl4 verilen Grup
II’ye göre CCl4+meryemana dikeni ve CCl4+zerdeçal verilen grupların serum ve karaciğer MDA ve NO düzeylerinde anlamlı bir değişim gözlenmedi. Kontrol, meryemana dikeni ve zerdeçal verilen
grupların değerleri karşılaştırıldığında serum biyokimya değerlerinde anlamlı bir değişme gözlenmedi.
Oluşan karaciğer hasarının geri döndürülmesi amacıyla çalışmamızda kullanılan, zerdeçal ve meryemana dikeni uygulaması aynı
maddelerin değişik dozlarda verilerek yapılacak yeni araştırmalar
ve etkilerinin belirlenmesine ihtiyaç olduğu sonucunu çıkarmıştır

Keywords

Karaciğer hasarı, karbon tetraklorür, meryemana dikeni, rat, zerdeçal.

The Effects of Curcuma Longa and Silybum Marianum on Carbon Tetrachloride Induced Chronic Hepatic Damage in Rats

Abstract

This study aims to evaluate the protective efficacy of Curcuma
longa and Silybum marianum on lipid peroxidation and some serum biochemical parameters in liver damage induced with carbon
tetrachloride (CCl4) in rats.
In the study, 60 4 month old Wistar albino rats weighing 250gr on
average were used. Application of the treatment in the control
groups were performed with three groups. The group I was administered corn oil twice for one week, group V was administered 100
mg/kg silymarin and group VI was administrated 80 mg/kg turmeric for 12 weeks by oral gavage. In the experimental group, 0,5
ml/kg CCl4 was injected intraperitoneally twice a week (Group II).
The application of the treatment was performed in two groups for
12 weeks in the treatment groups. While the 100 mg/kg silymarin
was given in the CCl4+silymarin group by gavage (Group III), the 80
mg/kg turmeric was given in the CCl4+turmeric group following of
the injection of 0,5 ml/kg CCl4 (Group IV). At the end of the study,
all liver tissues were examined with both histopathological and
serum biochemical parameters. While the normal tissue structure
was observed in the control group in the histopathological examination of the experimental and control groups, it was shown that
there were fatty degeneration in the hepatocytes, deterioration in
the structure of remark cords, hepatocyte degeneration, mononuclear cell infiltration areas composed of majority lymphocytes in
the portal area and parenchyma, especially at portal area increasing connective tissue spread to parenchyma due to formation of
lobulation. The liver lesions were found in the CCl4+silymarin and
CCl4+turmeric groups as in Group II. While serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), low density lipoprotein (LDL) levels, liver malondialdehyde (MDA) and
nitric oxide (NO) were increased in the CCl4-treated groups; the
levels of high-density lipoprotein (HDL) and albumin values were
decreased compared to the control group. When compared with the
CCl4-treated group, it was observed that there was no statistically
significant difference in the serum levels of CCl4+silymarin and
CCl4+turmeric groups. It was observed that the serum biochemistry
parameters were not significant change in the silymarin and turmeric groups compared with control group.
In this study it has been concluded that there is a need for future
studies in which different doses of silymarin and turmeric are used
to reverse the liver damage and determine their efficacy.

Keywords

Carbon tetrachloride, curcuma longa, hepatotoxicity, rat, silybum marianum

References

• 1. Dündar Y. Fitokimyasallar ve sağlıklı yaşam. Kocatepe Tıp Dergisi 2001; 2:131-138.
• 2. Burroughs AK, Westaby D. Liver, biliary tract and pancreatic disease. In: Kumar P, Clark M (eds), Clinical Medicine. 6 th ed. Elsevier Saunders, 2005; pp 347-417.
• 3. Moeller RB. Hepatobiliary system. In: Plumlee KH. (ed), Clinical Veterinary Toxicology. United States 2004: pp 61-62.
• 4. Sherlock S. Chronic hepatitis and cirrhosis. Hepatology 1984; 4:5-28.
• 5. Natarajan SK, Thomas S, Ramamoorthy P, et al. Oxidative stress in the development of two different experimental models. J Gastroen Hepatol 2006; 21:947-957.
• 6. McCord JM. The evolution of free radicals and oxidative stress. Am J Meb 2000; 108:652. 7. Betteridge DJ. What is oxidative stress? Metabolism 2000; 49:3-8.
• 8. Aruoma OI. Nutrition and health aspects of free radicals and antioxidants. Food Chem, 1994; 32:671-683.
• 9. Halliwell B. How to characterize a biological antioxidant. Free Radical Res Commun 1990; 9:1-32.
• 10. Southorn PA, Powis G. Free radicals in medicine. Chemical 1988; 29:1516-1523.
• 11. Sies H. Oxidative stress: Oxidants and antioxidants. Exp Physiol 1997; 82:291-295.
• 12. Palmieri B, Sblendorio V. Oxidative stress detection: What for? Eur Rev Med Pharmacol Sci 2006; 10:291-317.
• 13. Moure A, Cruz JM, Franco D, et al. Natural antioxidants from residual sources. Food Chemistry 2001; 72:145-171.
• 14. Naczk M, Shahidi F. Extraction and analysis of phenolics in food. Journal of Chromatography 2004; 1054:95-111.
• 15. Muriel P, Espinoza YR. Beneficial drugs for liver disease: A review. J Appl Toxicol 2008; 28:93-103.
• 16. Anthony KP, Saleh MA. Free radical scavenging and antioxidant activities of silymarin components. Antioxidants 2013; 2:398-407.
• 17. Muriel P, Mourelle M. Prevention by silymarin of membrane alterations in acute carbon tetrachloride liver damage. J Appl Toxicol 1990; 10:275-279.
• 18. Wang DH, Ishii K, Zhen LX, Taketa K. Enhanced liver injury in acatalasemic mice following exposure to carbon tetrachloride. Arch Toxicol 1996; 70:189-194.
• 19. Eminzade S, Uras F, Izzettin FV. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr Metab 2008; 5:18.
• 20. Das KC, Das CK. Curcumin (diferuloylmethane), a singlet oxygen (1O2) quencher. Biochemical and Biophysical Research Communications 2002; 295,62–66.
• 21. Naik SR, Thakare VN, Paitl SR. Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: Evidence of its antioxidant property. Exp Toxicol Pathol 2011; 63:419-431.
• 22. Maheswari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: A short review. Life Sci 2006; 78:2081-2087.
• 23. Ammon HP, Walh MA. Pharmacology of Curcuma longa. Planta Med 1991; 57:1-7.
• 24. Luper S. A review of plants used in the treatment liver disease. Altern Med Rev 1998; 3:410-421.
• 25. Sung-Hwa K, Ho JC, Nari Y, Oh ST, Shin E, Shim KS, Lee SM. Protective effect of a mixture of Aloe vera and Silybum marianum against carbon tetrachloride induced acute hepatotoxicity and liver fibrosis. J Pharmacol Sci 2009; 109:119-127.
• 26. Kamalakkannan N, Rukkumani R, Varma PS, Viswanathan P, Rajasekharan KN, Menon VP: Comparative effects of curcumin and an analogue of curcumin in carbon tetrachloride induced hepatotoxicity in rats. Basic Clin Pharmacol 2005; 97:15- 21.
• 27. Lowry OH, Rosebrough NJ, Farr AL Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193:265-75.
• 28. Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 1993; 84:407.
• 29. Yoshioka T, Kawada K, Shimada T. Lipid peroxidation in material and cord blood and protective mechanism against activatedoxygen toxicity in the blood. Am J Obstet Gynecol 1979; 135:372-376.
• 30. Tracey WR, Tse J, Carter G. Lipopolysaccharideinduced changes in plasma nitrite and nitrate concentrations in rats and mice: Pharmacological evaluation of nitric oxide synthase inhibitors. J Pharmacol Exp Ther 1995; 272:1011-1015.
• 31. Shimiziu I. Antifibrogenic therapies in chronic HCV infection. Curr Drug Targets Infect Disord 2001; 1:227-240.
• 32. Hagerman AE, Riedl KM, Jones GA, Sovik KN, Ritchard NT, Hartzfeld PW, Riechel TL. High molecular weight plant polyphenolics (tannins) as biological antioxidants. J Agric Food Chem 1998; 46:1887-1892.
• 33. Fu Y, Zheng S, Lin J, Ryerse J, Chen A. Curcumin protects the rat liver from CCl4 caused injury and fibrogenesis by attenuating oxidative stres and suppressing inflammation. Mol Pharmacol 2008; 73:399-409.
• 34. Kevin PA, Mahmoud AS. Free radical scavenging and antioxidant activities of silymarin components. Antioxidants 2013; 2:398-407.
• 35. Tamayo RP. Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis? Hepatology 1983; 3:112-120.
• 36. Recknagel RO, Glende EA, Dolak JA, Waller RL. Mechanism of carbon tetrachloride toxicity. Pharmacol Ther 1989; 43:139-154.
• 37. Sarhan NAZ, El-Denshary ES, Hassan NS, AbuSalem FM, Abdel-Wahhab MA. Isoflavones enriched soy protein prevents CCl4-induced hepatotoxicity in rats. ISRN Pharmacol 2012; 8.
• 38. Eidi A, Mortazavi P, Behzadi K, Rohani AH, Safi S. Hepatoprotective effect of manganese chloride against CCl4-induced liver injury in rats. Biol Trace Elem Res 2013; 155:267-275.
• 39. Lee TY, Wang GJ, Chiu JH, Lin HC. Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride induced hepatic fibrosis in rats. J Pharm Pharmacol 2003; 55:1561-1568.
• 40. Kus I, Ogeturk M, Oner H, Sahin S, Yekeler H, Sarsilmaz M. Protective effects of melatonin against carbontetrachloride induced hepatotoxicity in rats: A light microscopic and biochemical study. Cell Biochem Funct 2005; 23:169-174.
• 41. Chamulitrat W, Jordan SJ, Mason RP. Nitric oxide production during endotoxic shock in carbon tetrachloride treated rats. Mol Pharm 1994; 46:391- 397.
• 42. Srinivasan M, Rukkumani A. Sudheer R, Menon VP. Ferulic acid, a natural protector against carbon tetrachloride induced toxicity. Fundam Clin Pharmacol 2005; 19:491-496.
• 43. Yılmaz S, Bahçecioğlu İH. Karbon tetraklorür ile siroz oluşturulmuş ratlarda lipid peroksidasyonu, antioksidan enzim ve pirüvat kinaz aktiviteleri. Turk J Vet Anim Sci 2000; 24:25-28.
• 44. Wu SJ, Lin YH, Chu CC, Tsai YH, Chao JCJ. Curcuminor saikosaponin a improves hepatic antioxidant capacity and protects against CCl4-induced liver injury in rats. J Med Food 2008; 11:224-229.
• 45. Rajesh MG, Latha MS. Preliminary evaluation of the antihepatotoxic activity of Kamilari, a polyherbal formulation. J Ethanopharmacol 2004; 91:99-104.
• 46. Muriel P, Moreno MG, Hernandez MC, Chávez E, Alcantar LK. Resolution of liver fibrosis in CCl4 administration in the rat after discontinuation of treatment: Effect of silymarin, silibinin, colchicine and trimethyl colchicinic acid. Basic Clin Pharmacol Toxicol 2005; 96:375-380.
• 47. Tsai JH, Liu JY, Wu TT, et al. Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats. J Viral Hepatitis 2008; 15:508- -514.
• 48. Park EJ, Jeon CH, Ko G, Kim J, Sohn DH. Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. J Pharm Pharmacol 2000; 52:437-440.