Araştırma Makalesi
Ratlarda Karbon Tetraklorür (CCl4) ile Oluşturulan Kronik Karaciğer Hasarı Üzerine Susam Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi
Öz
Ratlarda deneysel olarak oluşturulan karbon tetraklorür (CCl4) toksikasyonunda susam yağının (SY) olası koruyucu etkisi, hücresel apoptozda kaspaz 3 aktivasyonu, serum alanin amino transferaz (ALT) aktivitesi, trigliserid, total protein, albümin, total kolesterol düzeyleri ve karaciğer malondialdehit ile total antioksidan kapasitesi değerlendirildi. Çalışmada 48 adet rat, 12 hayvandan oluşan 4 gruba ayrıldı. Grup I kontrol grubudur. Grup II CCl4 grubu olup, intraperitoneal 0,2 ml/kg CCl4, haftada iki kere 8 hafta uygulandı. Grup III SY grubudur ve 8 ml/kg susam yağı, 12 hafta gavaj şeklinde uygulandı. Grup IV CCl4+SY grubu olup, 8 ml/kg susam yağı, 12 hafta gavaj yoluyla uygulanırken son 8 hafta, haftada 2 defa intraperitoneal yolla 0,2 ml/kg CCl4 uygulandı. Histopatolojik olarak Grup I ve Grup III’de karaciğer normal görünümde olup; Grup II’de hepatositlerde yoğun makro-mikroveziküler yağlanma, parankimde mononüklear hücre infiltrasyonları, bağ doku artışına bağlı tam olmayan pseudolobulasyon gözlendi. Grup IV’de ki histopatoloji Grup II ile benzerdi. İmmunohistokimyasal incelemede, kontrol gruplarına göre çalışma grubunda kaspaz 3 aktivitesinin arttığı gözlendi. Grup II’de artan serum ALT aktivitesi, Grup IV’de değişmedi. Grup II’de serum total protein ve albümin düzeylerindeki azalma istatistiksel olarak anlamlı olup (P<0,001), Grup IV’de sayısal olarak azaldı. Grup IV’de önemli düzeyde artış gösteren serum total kolestrol düzeyleri, SY’den etkilenmedi. Grup II’de serum trigliserit düzeylerinin istatistiki önemde artış (P<0,001), Grup IV’de sayısal olarak düşürdü. Grup IV’de SY ilavesi malondialdehit ve total antioksidan kapasitesi düzeyleri yönünden etki göstermedi. Grup IV’de susam yağının antioksidan özelliklerinin biyokimyasal veriler, histopatolojik lezyonlar üzerine iyileştirici yönden anlamlı bir etkisi gözlenmedi.
Anahtar Kelimeler
Destekleyen Kurum
Erciyes Üniversitesi Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiş ve yüksek lisans tezinden üretilmiştir.
Proje Numarası
TYL-2018-8449
Kaynakça
- Referans1 Abdel-Daim MM, Taha R, Ghazy EW, El-Sayed YS. (2015). Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies. Can J Physiol Pharm; 94(1): 81-8.
- Referans2 Abdou HM, Hussien HM, Yousef MI. (2012). Deleterious effects of cypermethrin on rat liver and kidney: protective role of sesame oil. J Environ Sci Heal B; 47(4): 306-14.
- Referans3 Ahmed SK, Mohammed SA, Khalaf G, Fikry H. (2014). Role of bone marrow mesenchymal stem cells in the treatment of CCl4 induced liver fibrosis in albino rats: a histological and immunohistochemical study. Int J Stem Cells; 7(2): 87-97.
- Referans4 Akimoto K, Kitagawa Y, Akamatsu T, Hirose N, Sugano M, Shimizu S, Yamada H. (1993). Protective effects of sesamin against liver damage caused by alcohol or carbon tetrachloride in rodents. Ann Nutr Metab; 37(4): 218-24.
- Referans5 Aranda M, Albendea CD, Lostalé F, López‐Pingarrón L, Fuentes‐Broto L, Martínez‐Ballarín E, Garcia JJ. (2010). In vivo hepatic oxidative stress because of carbon tetrachloride toxicity: protection by melatonin and pinoline. J Pineal Res; 49(1): 78-85.
- Referans6 Atasever A, Yaman D. (2014). The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats. Exp Toxicol Pathol; 66(8): 361-5.
- Referans7 Azab EA. (2014). Hepatoprotective effect of sesame oil against lead induced liver damage in albino mice: Histological and biochemical studies. Amer J BioSci; 2(6-2): 1-11.
- Referans8 Balderas Renteria I, Camacho Corona M, Carranzo Rozales P. (2007). Hepatoprotective effect of Leucophyllum frutescens on Wistar albino rats intoxicated with carbon tetrachloride. Ann Hepatol; 6(4): 251-4.
- Referans9 Basu S. (2003). Carbon tetrachloride-induced lipid peroxidation: Eicosanoid formation and their regulation by antioxidant nutrients. Toxicology; 189 (1-2): 113-27.
- Referans10 Cengiz N, Kavak S, Güzel A, Özbek H, Bektaş H, Him A, Balahoroğlu R. (2013). Investigation of the hepatoprotective effects of Sesame (Sesamum indicum L.) in carbon tetrachloride-induced liver toxicity. J Membrane Biol; 246(1):1-6.
- Referans11 Chandrasekaran VRM, Wan CH, Liu LL, Hsu DZ, Liu MY. (2008). Effect of sesame oil against acetaminophen-induced acute oxidative hepatic damage in rats. Shock; 30(2): 217-21.
- Referans12 Crawford JM. (2003). Karaciğer ve safra yolları. In: Robbins Temel Patoloji (7. Baskı). Robbins SL, Cotran RS, Kumar V, editör(ler). Nobel Tıp Kitabevi, İstanbul, pp 591-630.
- Referans13 Domitrović R, Škoda M, Marchesi VV, Cvijanović O, Pugel EP, Štefan MB. (2013). Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. Food Chem Toxicol; 51: 370-78.
- Referans14 Eckle VS, Buchmann A, Bursch W, Schulte-Hermann R, Schwarz M. (2004). Immunohistochemical detection of activated caspases in apoptotic hepatocytes in rat liver. Toxicol Pathol; 32(1): 9-15.
- Referans15 Evans GO. (2009). Animal Clinical Biochemistry. 2nd ed. USA: Taylor & Francis Group.
- Referans16 Feroz Khan Z, Asdaq SMB, Prasanna Kumar SR. (2009). Effects of few Indian medicinal herbs on carbon tetrachloride induced hepatic injury in animals. Int J Pharm Tech Res; 1(3): 579-87.
- Referans17 Gnanaprakash K, Madhusudhana Chetty C, Ramkanth S, Alagusundaram M, Tiruvengadarajan Vs, Angala Parameswari S, Mohamed Saleem Ts. (2010). Aqueous extract of Flacourtia indica prevents carbon tetrachloride induced hepatotoxicity in rat. Int J Biol Sci; 4(1): 51-5.
- Referans18 Gutiérrez R, Alvarado JL, Presno M, Pérez Veyna O, Serrano CJ, Yahuaca P. (2010). Oxidative stress modulation by Rosmarinus officinalis in CCl4-induced liver cirrhosis. Phytother Res; 24(4): 595-601.
- Referans19 Hirose N, Doi F, Ueki T, Akazawa K, Chijiiwa K, Sugano M, Yamada H. (1992). Suppressive effect of sesamin against 7, 12-dimethylbenz [a]-anthracene induced rat mammary carcinogenesis. Anticancer Res; 12(4): 1259-65 Referans20 Hsu DZ, Chen KT, Chien SP, Li YH, Huang BM, Chuang YC, Liu MY. (2006). Sesame oil attenuates acute iron-induced lipid peroxidation-associated hepatic damage in mice. Shock; 26(6): 625-30.
- Referans21 Hsu DZ, Liu MY. (2004). Sesame oil protects against lipopolysaccharide-stimulated oxidative stress in rats. Crit Care Med; 32(1): 227-31.
- Referans22 İlhan N, Seçkin D. (2005) Protective effect of Nigella sativa seeds on CCl4-induced hepatotoxicity. FÜ Sağ Bil Tıp Derg; 19(3): 175-9.
- Referans23 Kalaycıoğlu L, Serpek B, Nizamlıoğlu M, Başpınar N, Tiftik AM. (2000). Biyokimya. Nobel Yayın Dağıtım Ltd. Şti, Ankara.
- Referans24 Kamal Eldin A, Frank J, Razdan A, Tengblad S, Basu S, Vessby B. (2000). Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats. Lipids; 35(4): 427-35.
- Referans25 Khattab AH, El Tinay AH, Khalifa HA, Mirghani S. (1974). Stability of peroxidised oils and fat to high temperature heating. J Sci Food Agric; 25(6): 689-96.
- Referans26 Khorshid HR, Azonov JA, Novitsky YA, Farzamfar B, Shahhosseiny MH. (2008). Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats. Indian J Gastroenterol; 27(3): 110-2.
- Referans27 Kumar M. (2011). Hepatoprotective activity of Sesamum Indicum Linn. against CCl4-induced hepatic damage in rats. Int J Pharm Biol Arch; 2(2): 710-5.
- Referans28 Lida C, Fujii K, Koga E, Washino Y, Kitamura Y, Ichi I, Kojo S. (2009). Effect of alpha-tocopherol on carbon tetrachloride intoxication in the rat liver. Arch Toxicol; 83(5): 477-83.
- Referans29 Lv D, Zhu CQ, Liu L. (2015). Sesamin ameliorates oxidative liver injury induced by carbon tetrachloride in rat. Int J Clin Exp Patho; 8(5): 5733-8.
- Referans30 Lv P, Luo HS, Zhou XP, Paul SC, Xiao YJ, Si XM, Liu SQ. (2006). Thalidomide prevents rat liver cirrhosis via inhibition of oxidative stress. Pathol Res Pract; 202(11): 777-88.
- Referans31 Manibusan MK, Odin M, Eastmond DA. (2007). Postulated carbon tetrachloride mode of action: A review. J Environ Sci Heal C; 25(3): 185-209.
- Referans32 Munish K, Sisodia SS, Anjoo K, Vaibhav R. (2011). Evaluation of hepatoprotective effect of Sesamum indicum Linn. seed extract against paracetamol induced hepatotoxicity in rats. Int J Pharm Clin Res; 3(3): 66-9.
- Referans33 Muriel P, Escobar Y. (2003). Kupffer cells are responsible for liver cirrhosis induced by carbon tetrachloride. J Appl Toxicol; 23(2): 103-8.
- Referans34 Muriel P, Mourelle M. (1990). Prevention by silymarin of membrane alterations in acute CCl4 liver damage. J Appl Toxicol; 10(4): 275-9.
- Referans35 Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J. (2000). Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature; 403(6765): 98-103.
- Referans36 Niki E, Yoshida Y, Saito Y, Noguchi N. (2005). Lipid peroxidation: Mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun; 338(1): 668-76.
- Referans37 Parajuli DR, Park EJ, Che XH, Jiang WY, Kim YC, Sohn D, Lee SH. (2013). PF2401-SF, standardized fraction of Salvia miltiorrhiza, induces apoptosis of activated hepatic stellate cells in vitro and in vivo. Molecules; 18(2): 2122-34.
- Referans38 Periasam S, Liu CT, Chien SP, Chen YC, Liu MY. (2016). Daily sesame oil supplementation mitigates ketoconazole-induced oxidative stress-mediated apoptosis and hepatic injury. J Nutr Biochem; 37: 67-75.
- Referans39 Recknagel RO, Glende EA Jr, Dolak JA, Waller RL. (1989). Mechanisms of carbon tetrachloride toxicity. Pharmacol Therapeut; 43(1): 139-54.
- Referans40 Soliman MM, Attia HF, El-Ella GAA. (2015). Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: protection by sesame oil. Int J Immunopath Pharmacol; 28(4): 508-20.
- Referans41 Tao LL, Cheng YY, Ding D, Mei S, Xu JW, Yu J, Xu ZD. (2012). C/EBP-α ameliorates CCl4-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo. Apoptosis; 17(5): 492-502.
- Referans42 Tasci I, Mas N, Mas MR, Tuncer M, Comert B. (2008). Ultrastructural changes in hepatocytes after taurine treatment in CCl4 induced liver injury. World J Gastroenterol; 14(31): 4897-902.
- Referans43 Venukumar MR, Latha MS. (2002). Hepatoprotective effect of the methanolic extract Curculigo orchioides in CCl4 treated male rats. Indian J Pharmacol; 34(2): 269-75.
- Referans44 Xie J, Liu J, Chen TM. (2015). Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. World J Gastroenterol; 21(18): 5473-81.
- Referans45 Yehia HM, Al Olayan EM, Elkhadragy MF. (2013). Hepatoprotective role of the pomegranate (Punica granatum) juice on carbon tetrachloride induced oxidative stress in rats. Life Sci J; 10(4): 1534-44.
- Referans46 Zuinen R, Yamaji K, Aoki M, Chikuma T, Hojo H. (2007). Early induced, high-level interleukin-6 expression in the rat peritoneal cavity into which a hepatotoxicant carbon tetrachloride was administered. Toxicol Lett; 170(1): 42-8.
Toplam 45 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Veteriner Cerrahi |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Proje Numarası | TYL-2018-8449 |
| Yayımlanma Tarihi | 30 Aralık 2020 |
| Yayımlandığı Sayı | Yıl 2020Cilt: 5 Sayı: 3 |
