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Ratlarda karbon tetraklorür ile oluşturulan kronik karaciğer hasarı üzerine biberiye ekstraktının (Rosmarinus officinalis) etkisi ve hepatik apoptozisin belirlenmesi

Yıl 2019, Cilt: 28 Sayı: 3, 110 - 117, 30.12.2019
https://doi.org/10.34108/eujhs.558310

Öz

Amaç: Çalışmada,
karbon tetraklorür (CCl4) ile kronik karaciğer hasarı oluşturulan
ratlarda Biberiye (BE)  ekstraktının
koruyucu etkisi, hücresel apoptozun kaspaz 3, 8 ve 9 antikorları ile
değerlendirilmesi ve serum ALT (alanin amino transferaz) aktivitesi,
Trigliserit, Total protein, Albümin, total Kolesterol,  karaciğer MDA (malondialdehit) düzeyleri ile
Total antioksidan kapasitesi (TAK) belirlendi.

Gereç
ve Yöntem:
Çalışmada, 40 adet (200-250 gr) Wistar albino erkek
rat, 10’arlı 4 gruba ayrıldı. İlk grup kontrol olup % 0,9 NaCl (0,2 mL/kg/canlı
ağırlık) uygulandı. İkinci gruba 12 hafta her gün sırası ile 200 mg/kg/canlı
ağırlık dozunda biberiye ekstraktı gavajla verildi. Üçüncü gruba 8 hafta
boyunca haftada 2 kez 1:1 oranında mısır yağı ile dilüe edilen CCl4
(İP) 0,2 mL/kg/canlı ağırlık dozun da enjekte edildi. Dördüncü gruba 12 hafta
her gün 200 mg/kg/canlı ağırlık dozunda biberiye ekstraktı gavajla verilirken
aynı gruba beşinci hafta dahil 8 hafta intraperitoneal (İP) 0,2 mL/kg/canlı
ağırlık olarak haftada iki doz CCl4 uygulandı.

Bulgular:
Grup
I ve II’de karaciğer dokusu normal yapıda; Grup III’de hepatositlerde yoğun
makro-mikroveziküler yağlanma, parankimde çoğunluğu lenfositlerden oluşan mononüklear
hücre infiltrasyonları, nekroz, portal hafif fibrozis ile parankimde pseudolobulasyon
görüldü. Grup IV’de  bulgular da kısmi
azalmaya rağmen Grup III’e benzer histoloji dikkati çekti. Grup I ve II’de  kaspaz 3, 9 pozitif  8 negatifti. Grup III ve VI’de kaspaz 3, 8 ve
9 pozitifti.  Grup IV’de kaspaz-3 gibi
kaspaz-9’unda ve kısmen azalmış olması, biberiye ekstraktının sınırlı da olsa
karaciğer dokusunu koruyabileceğini düşündürmüştür. Grup III’de artmış serum
ALT aktivitesi Grup IV’de normal değerlere yaklaştı. Grup III’de ki serum
trigliserit düzeylerindeki artışlar (P=0,001), Grup IV’de sayısal olarak
azaldı. Grup III’de MDA seviyesi yüksek (P<0,05), TAK seviyesi düşükken,  Grup IV’de MDA seviyesi önemli düzeyde düşüş
(P<0,001).







Sonuç: Grup
IV’de biyokimyasal veriler karaciğer hasarının iyileştiği gösterirken,
histopatolojik lezyonlar üzerine olumlu bir etki gözlenmemiştir.
Bu nedenle
biberiye ekstresinin farklı sürelerde ve yan etki oluşturmaksızın en iyi sonucu
verecek yüksek dozlarda kullanılarak, etkisinin belirlenmesine yönelik yeni
araştırmalara ihtiyaç olduğu kanaatine varıldı.

Kaynakça

  • Referans1 Crawford JM. Karaciğer ve safra yolları. Robbins SL, Cotran RS, Kumar V. eds. In: Robbins Temel Patoloji. 7. Baskı, İstanbul: Nobel Tıp Kitabevi, 2003; pp. 591-630.
  • Referans2 Recknagel RO, Glende EA Jr, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol Therapeut 1989; 43: 139-54.
  • Referans3 Muriel P, Mourelle M. Prevention by silymarin of membrane alterations in acute CCl4 liver damage. J Appl Toxicol 1990; 10: 275-9.
  • Referans4 Basu S. Carbon tetrachloride-induced lipid peroxidation: Eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 2003; 189: 113-27.
  • Referans5 Manibusan MK, Odin M, Eastmond DA. Postulated carbon tetrachloride mode of action: A review. J Environ Sci Heal C 2007; 25: 185-209.
  • Referans6 Singh RP, Chidambara Murthy KN, Jayaprakasha GK. Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J Agric Food Chem 2002; 50: 81-6.
  • Referans7 Breikaa RM, Algandaby MM, El Demerdash E, Abdel Naim AB. Biochanin a protects against acute carbon tetrachloride-induced hepatotoxicity in rats. Biosci Biotechnol Biochem 2013; 77: 909-16.
  • Referans8 Dündar Y. Fitokimyasallar ve sağlıklı yaşam. Kocatepe Tıp Derg 2001; 2: 131-8.
  • Referans9 Abdel Wahhab El Deen KG, El Shamy KA, El Zizz El Beih NA, Morcy FA, Mannaa FAE. Protective effect of a natural herb (Rosmarinus officinalis) against hepatotoxicity in male albino rats. Commun Sci 2011; 2: 9-17.
  • Referans10 Yehia HM, Al Olayan EM, Elkhadragy MF. Hepatoprotective role of the pomegranate (Punica granatum) juice on carbon tetrachloride induced oxidative stress in rats. Life Sci J 2013; 10: 1534-44.
  • Referans11 Kaur G, Jabbar Z, Athar M, Alam MS. PuniFca granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food Chem Toxicol 2006; 44: 984-93.
  • Referans12 Chidambara MKN, Jayaprakasha GK, Singh RP. Studies on antioxidant activity of pomegranate (Punica granatum) peel extract using in vivo models. J Agric Food Chem 2002; 50: 4791-5.
  • Referans13 Gutiérrez R, Alvarado JL, Presno M et al. Oxidative stress modulation by Rosmarinus officinalis in CCl4 -induced liver cirrhosis. Phytother Res 2010; 24: 595-601.
  • Referans14 Green Cj, Kneight J, Precious S, Simpkin S. Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience. Lab Anim, 1981; 15: 163-170.
  • Referans15 Luna LG, eds. Manual of Histologic Staining Methods; of the Armed Forces Institute of Pathology. New York Blakiston Division, McGraw-Hill, 1968; pp. 34-75.
  • Referans16 Çiçek B, Oğuz D, Erden E, Şahin T. Nonalkolik steatohepatitte histolojik hasarı öngörüde klinik ve laboratuvarın yeri. Akad Gastroenterol Derg 2002; 1: 1-7.
  • Referans17 Schwimmer JB, Behling C, Newbury R et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005; 42: 641-9.
  • Referans18 Feroz Khan Z, Asdaq SMB, Prasanna Kumar SR. Effects of few Indian medicinal herbs on carbon tetrachloride induced hepatic injury in animals. International J Pharm Tech Res, 2009; 1: 579-587.
  • Referans19 Venukumar MR, Latha MS. Hepatoprotective effect of the methanolic extract Curculigo orchioides in CCl4 treated male rats. Indian J Pharmacol, 2002; 34: 269-275.
  • Referans20 Lv P, Luo HS, Zhou XP et al. Thalidomide prevents rat liver cirrhosis via inhibition of oxidative stress. Pathol Res Pract 2006; 202: 777-788.
  • Referans21 Tasci I, Mas N, Mas MR, Tuncer M, Comert B. Ultrastructural changes in hepatocytes after taurine treatment in CCl4 induced liver injury. World J Gastroenterol 2008; 14: 4897-4902.
  • Referans22 Brattin WJ, Glende EA, Recknagel RO. Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radical Bio Med 1985; 1: 27-38.
  • Referans23 Yaman D, Atasever A. Karbon Tetraklorür ile Oluşturulan Akut ve Kronik Karaciğer Hasarı Üzerine Biberiye Ekstraktının (Rosmarinus officinalis) Etkisi. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, 2016; 13(2): 83-100.
  • Referans24 Gnanaprakash K, Madhusudhana CC, Ramkanth S. Aqueous extract of Flacourtia indica prevents carbon tetrachloride induced hepatotoxicity in rat. Int J Biol Sci, 2010; 6: 51-55.
  • Referans25 Aranda M, Albendea CD, Lostalé F et al. In vivo hepatic oxidative stress because of carbon tetrachloride toxicity: protection by melatonin and pinoline. J Pineal Res 2010; 49: 78-85.
  • Referans26 Santra A, Chowdhury A, Ghatak S, Biswas A, Dhali GK. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine. Toxicol Appl Pharmacol, 2007; 220: 146-155.
  • Referans27 Löliger J. Natural antioxidants. In: Allen JC, Hamilton RJ (eds), Rancidity in foods. Applied Science Publishers, London, 1983: 89-107.
  • Referans28 Rižnar K, Čelan Š, Knez Ž et al. Antioxidant and antimicrobial activity of rosemary extract in chicken frankfurters. J Food Sci 2006; 71: 425-429.
  • Referans29 Abdel Wahhab El Deen KG, El Shamy KA, El Zizz El Beih NA, Morcy FA, Mannaa FAE. Protective effect of a natural herb (Rosmarinus officinalis) against hepatotoxicity in male albino rats. Commun Sci 2011; 2: 9-17.
  • Referans30 Fahim FA, Esmat AY, Fadel HM, Hassan KF. Allied studies on the effect of Rosmarinus officinalis L. on experimental hepatotoxicity and mutagenesis. Int J Food Sci Nutr 1999; 50: 413-427.
  • Referans31 Amin A, Hamza AA. Hepatoprotective effects of hibiscus, rosmarinus and salvia on azathioprine-induced toxicity in rat. Life Sci 2005; 77: 266-278.
  • Referans32 Botsoglou NA, Taitzoglou IA, Botsoglou E et al. Effect of long-term dietary administration of oregano and rosemary on the antioxidant status of rat serum, liver, kidney and heart after carbon tetrachloride-induced oxidative stress. J Sci Food Agric 2009; 89: 1397-1406.
  • Referans33 Sakr SA, El-Abd SF, Mohamed Osman M, Kandil AK, Helmey MS. Effect of rosemary on carbontetrachloride-induced hepatotoxicity in albino rats: Histological and Biochemical Studies. Egypt. J. Exp. Biol 2010; 6(1): 135-140.
  • Referans34 Sotelo-Felix JI, Martinez-Fong D, Muriel P, De La Torre P. Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat. J Ethnopharm 2002; 81: 145- 154.
  • Referans35 Higuchi H, Gores GJ. Mechanisms of liver injury: an overview. Curr Mol Med. 2003; 3: 483-490.
  • Referans36 Wright MC, Issa R, Smart DE, Trim N, Murray GI, Primrose JN, Arthur MJ, Iredale JP, Mann DA. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology 2001;121:685-698.
  • Referans37 Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatology 2004; 39: 273-278.
  • Referans38 Bilodeau M. Liver cell death: update on apoptosis. Can J Gastroenterol 2003; 17: 501-506.
  • Referans39 Leach AP. Apoptosis molecular mechanism for physiological cell death in health and disease. Clin Lab Sci 1998; 11: 346-349.
  • Referans40 Shi J, Aisaki K, Ikawa Y, Wake K. Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am J Pathol 1998; 153: 515–525.
  • Referans41 Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 2000; 403(6765), 98.
  • Referans42 Tao LL, Cheng YY, Ding D, et al. 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 2012; 17(5), 492-502.
  • Referans43 Domitrović R, Škoda M, Marchesi VV, et al. Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. Food and chemical toxicology 2013; 51, 370-378.
  • Referans44 Karakus E, Karadeniz A, Simsek N ve ark. Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4). Journal of hazardous materials 2011; 195: 208-213.
  • Referans45 Liu H, Wang Z, Nowicki MJ. Caspase-12 mediates carbon tetrachloride-induced hepatocyte apoptosis in mice. World Journal of Gastroenterology: WJG 2014; 20(48), 18189.
  • Referans46 Aram G, Potter JJ, Liu X, Torbenson MS, Mezey E. Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration. Hepatology 2008; 47(6), 2051-2058.
  • Referans47 Chan CC, Lee KC, Huang YH, et al. Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury. Journal of gastroenterology and hepatology 2014; 29(3), 603-613.
  • Referans48 Leu JI, Crissey MAS, Taub R. Massive hepatic apoptosis associated with TGF-β1 activation after Fas ligand treatment of IGF binding protein-1–deficient mice. The Journal of clinical investigation 2003; 111(1), 129-139.
  • Referans49 Lu B, Xu Y, Xu L, et al. Mechanism investigation of dioscin against CCl4-induced acute liver damage in mice. Environmental toxicology and pharmacology 2012; 34(2), 127-135.
  • Referans50 Xie J, Liu J, Chen TM, et al. Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. World Journal of Gastroenterology: WJG 2015; 21(18), 5473.
  • Referans51 Parajuli DR, Park EJ, Che XH, et al. PF2401-SF, standardized fraction of Salvia miltiorrhiza, induces apoptosis of activated hepatic stellate cells in vitro and in vivo. Molecules 2013; 18(2), 2122-2134.

Effect of rosemary extract on chronic liver damage induced by carbon tetrachloride in rats and determination of hepatic apoptosis

Yıl 2019, Cilt: 28 Sayı: 3, 110 - 117, 30.12.2019
https://doi.org/10.34108/eujhs.558310

Öz

Purpose: The present study determined the possible protective effects of
rosemary extract on lesions and cellular apoptosis detection by
immunohistochemical method (with caspase 3, 8 and 9 antibodies) in liver tissue
and some biochemical parameters; serum ALT (alanin aminotransferase) activity,
triglyceride, total protein, albumin and cholesterol activity,  and liver MDA (malondialdehyde) levels along
with total antioxidant capacity on chronic liver injury induced by carbon
tetrachloride (CCl4) in rats.

Materials and Methods: Fourty Wistar albino rats (200-250 g) were divided
into four groups (n:10/group). In the first group of control rats (control
group), the rats were administered with %0,9 NaCl (0.2 mL/kg). The second group
was administered daily with 200 mg/kg rosemary extract for twelve weeks through
gastric gavage, respectively. Third group was also given CCl4
(which was diluted with corn oil, 1:1) i.p. (0,2 mL/kg) twice for 8 weeks. The
rats in the fourth group rats also received 200 mg/kg rosemary extract daily
for twelve weeks through gastric gavage and also given CCl4 (which was
diluted with corn oil, 1:1) i.p. (0,2 mL/kg) twice for 8 weeks, starting from
the 5th week.

Results: The
livers of the rats in group I and II had normal architecture, while an
intensive macro and microvesicular steatosis, mononuclear inflammatory cell
infiltrations mostly lymphocytes in portal area and paranchyma with necrotic
alterations, mild to severe fibrosis with lobulation formation were observed in
the group III. In Group IV, histological findings similar to Group III were
noted despite partial reduction. In the group I and II, while caspase-3 and
caspase-9 were positive, caspase-8 was negative. Caspase 3, caspase 8 and
caspase 9 were positive in the group III and IV. There was a limited reduction
in caspase 3 activity in group IV. Similar to caspase 3, partial reduction
observed in caspase 9 activity suggest that rosemary extract administrations
may have a partial protective effect on the liver tissue. Increased serum ALT
activity level due to group IIIadministration was close to normal
in group IV. Increased serum triglyceride levels in Group III were decreased
numerically in Group IV.
In Group III, the MDA levels were high and TAC levels were
low. Compared to controls, serum triglyceride levels in CCl4 groups
were determined to be higher (P=0.001). Upon the administration of rosemary
extract, this value came down to lower numbers. 
MDA levels in in CCl4 group were higher than those of the other
groups (P<0.05). The. administration of rosemary extract to CCl4 group
reduced MDA levels significantly (P<0.001). There was no effect of rosemary
extract  administration on total
antioxidant capacity.
In Group IV, MDA level decreased significantly.







Conclusion: Biochemical data have shown that liver damage
improved in Group IV and no positive effect on histopathological lesions was
observed. Since biochemical parameter values were close to normal values in
groups which received rosemary extract compounds may have healing effects and therefore,
new research strategies and approaches where both compounds may be tried with
different periods in high doses without side effects are needed to evaluate
their effects.

Kaynakça

  • Referans1 Crawford JM. Karaciğer ve safra yolları. Robbins SL, Cotran RS, Kumar V. eds. In: Robbins Temel Patoloji. 7. Baskı, İstanbul: Nobel Tıp Kitabevi, 2003; pp. 591-630.
  • Referans2 Recknagel RO, Glende EA Jr, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol Therapeut 1989; 43: 139-54.
  • Referans3 Muriel P, Mourelle M. Prevention by silymarin of membrane alterations in acute CCl4 liver damage. J Appl Toxicol 1990; 10: 275-9.
  • Referans4 Basu S. Carbon tetrachloride-induced lipid peroxidation: Eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 2003; 189: 113-27.
  • Referans5 Manibusan MK, Odin M, Eastmond DA. Postulated carbon tetrachloride mode of action: A review. J Environ Sci Heal C 2007; 25: 185-209.
  • Referans6 Singh RP, Chidambara Murthy KN, Jayaprakasha GK. Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J Agric Food Chem 2002; 50: 81-6.
  • Referans7 Breikaa RM, Algandaby MM, El Demerdash E, Abdel Naim AB. Biochanin a protects against acute carbon tetrachloride-induced hepatotoxicity in rats. Biosci Biotechnol Biochem 2013; 77: 909-16.
  • Referans8 Dündar Y. Fitokimyasallar ve sağlıklı yaşam. Kocatepe Tıp Derg 2001; 2: 131-8.
  • Referans9 Abdel Wahhab El Deen KG, El Shamy KA, El Zizz El Beih NA, Morcy FA, Mannaa FAE. Protective effect of a natural herb (Rosmarinus officinalis) against hepatotoxicity in male albino rats. Commun Sci 2011; 2: 9-17.
  • Referans10 Yehia HM, Al Olayan EM, Elkhadragy MF. Hepatoprotective role of the pomegranate (Punica granatum) juice on carbon tetrachloride induced oxidative stress in rats. Life Sci J 2013; 10: 1534-44.
  • Referans11 Kaur G, Jabbar Z, Athar M, Alam MS. PuniFca granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food Chem Toxicol 2006; 44: 984-93.
  • Referans12 Chidambara MKN, Jayaprakasha GK, Singh RP. Studies on antioxidant activity of pomegranate (Punica granatum) peel extract using in vivo models. J Agric Food Chem 2002; 50: 4791-5.
  • Referans13 Gutiérrez R, Alvarado JL, Presno M et al. Oxidative stress modulation by Rosmarinus officinalis in CCl4 -induced liver cirrhosis. Phytother Res 2010; 24: 595-601.
  • Referans14 Green Cj, Kneight J, Precious S, Simpkin S. Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience. Lab Anim, 1981; 15: 163-170.
  • Referans15 Luna LG, eds. Manual of Histologic Staining Methods; of the Armed Forces Institute of Pathology. New York Blakiston Division, McGraw-Hill, 1968; pp. 34-75.
  • Referans16 Çiçek B, Oğuz D, Erden E, Şahin T. Nonalkolik steatohepatitte histolojik hasarı öngörüde klinik ve laboratuvarın yeri. Akad Gastroenterol Derg 2002; 1: 1-7.
  • Referans17 Schwimmer JB, Behling C, Newbury R et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005; 42: 641-9.
  • Referans18 Feroz Khan Z, Asdaq SMB, Prasanna Kumar SR. Effects of few Indian medicinal herbs on carbon tetrachloride induced hepatic injury in animals. International J Pharm Tech Res, 2009; 1: 579-587.
  • Referans19 Venukumar MR, Latha MS. Hepatoprotective effect of the methanolic extract Curculigo orchioides in CCl4 treated male rats. Indian J Pharmacol, 2002; 34: 269-275.
  • Referans20 Lv P, Luo HS, Zhou XP et al. Thalidomide prevents rat liver cirrhosis via inhibition of oxidative stress. Pathol Res Pract 2006; 202: 777-788.
  • Referans21 Tasci I, Mas N, Mas MR, Tuncer M, Comert B. Ultrastructural changes in hepatocytes after taurine treatment in CCl4 induced liver injury. World J Gastroenterol 2008; 14: 4897-4902.
  • Referans22 Brattin WJ, Glende EA, Recknagel RO. Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radical Bio Med 1985; 1: 27-38.
  • Referans23 Yaman D, Atasever A. Karbon Tetraklorür ile Oluşturulan Akut ve Kronik Karaciğer Hasarı Üzerine Biberiye Ekstraktının (Rosmarinus officinalis) Etkisi. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, 2016; 13(2): 83-100.
  • Referans24 Gnanaprakash K, Madhusudhana CC, Ramkanth S. Aqueous extract of Flacourtia indica prevents carbon tetrachloride induced hepatotoxicity in rat. Int J Biol Sci, 2010; 6: 51-55.
  • Referans25 Aranda M, Albendea CD, Lostalé F et al. In vivo hepatic oxidative stress because of carbon tetrachloride toxicity: protection by melatonin and pinoline. J Pineal Res 2010; 49: 78-85.
  • Referans26 Santra A, Chowdhury A, Ghatak S, Biswas A, Dhali GK. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine. Toxicol Appl Pharmacol, 2007; 220: 146-155.
  • Referans27 Löliger J. Natural antioxidants. In: Allen JC, Hamilton RJ (eds), Rancidity in foods. Applied Science Publishers, London, 1983: 89-107.
  • Referans28 Rižnar K, Čelan Š, Knez Ž et al. Antioxidant and antimicrobial activity of rosemary extract in chicken frankfurters. J Food Sci 2006; 71: 425-429.
  • Referans29 Abdel Wahhab El Deen KG, El Shamy KA, El Zizz El Beih NA, Morcy FA, Mannaa FAE. Protective effect of a natural herb (Rosmarinus officinalis) against hepatotoxicity in male albino rats. Commun Sci 2011; 2: 9-17.
  • Referans30 Fahim FA, Esmat AY, Fadel HM, Hassan KF. Allied studies on the effect of Rosmarinus officinalis L. on experimental hepatotoxicity and mutagenesis. Int J Food Sci Nutr 1999; 50: 413-427.
  • Referans31 Amin A, Hamza AA. Hepatoprotective effects of hibiscus, rosmarinus and salvia on azathioprine-induced toxicity in rat. Life Sci 2005; 77: 266-278.
  • Referans32 Botsoglou NA, Taitzoglou IA, Botsoglou E et al. Effect of long-term dietary administration of oregano and rosemary on the antioxidant status of rat serum, liver, kidney and heart after carbon tetrachloride-induced oxidative stress. J Sci Food Agric 2009; 89: 1397-1406.
  • Referans33 Sakr SA, El-Abd SF, Mohamed Osman M, Kandil AK, Helmey MS. Effect of rosemary on carbontetrachloride-induced hepatotoxicity in albino rats: Histological and Biochemical Studies. Egypt. J. Exp. Biol 2010; 6(1): 135-140.
  • Referans34 Sotelo-Felix JI, Martinez-Fong D, Muriel P, De La Torre P. Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat. J Ethnopharm 2002; 81: 145- 154.
  • Referans35 Higuchi H, Gores GJ. Mechanisms of liver injury: an overview. Curr Mol Med. 2003; 3: 483-490.
  • Referans36 Wright MC, Issa R, Smart DE, Trim N, Murray GI, Primrose JN, Arthur MJ, Iredale JP, Mann DA. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology 2001;121:685-698.
  • Referans37 Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatology 2004; 39: 273-278.
  • Referans38 Bilodeau M. Liver cell death: update on apoptosis. Can J Gastroenterol 2003; 17: 501-506.
  • Referans39 Leach AP. Apoptosis molecular mechanism for physiological cell death in health and disease. Clin Lab Sci 1998; 11: 346-349.
  • Referans40 Shi J, Aisaki K, Ikawa Y, Wake K. Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am J Pathol 1998; 153: 515–525.
  • Referans41 Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 2000; 403(6765), 98.
  • Referans42 Tao LL, Cheng YY, Ding D, et al. 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 2012; 17(5), 492-502.
  • Referans43 Domitrović R, Škoda M, Marchesi VV, et al. Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. Food and chemical toxicology 2013; 51, 370-378.
  • Referans44 Karakus E, Karadeniz A, Simsek N ve ark. Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4). Journal of hazardous materials 2011; 195: 208-213.
  • Referans45 Liu H, Wang Z, Nowicki MJ. Caspase-12 mediates carbon tetrachloride-induced hepatocyte apoptosis in mice. World Journal of Gastroenterology: WJG 2014; 20(48), 18189.
  • Referans46 Aram G, Potter JJ, Liu X, Torbenson MS, Mezey E. Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration. Hepatology 2008; 47(6), 2051-2058.
  • Referans47 Chan CC, Lee KC, Huang YH, et al. Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury. Journal of gastroenterology and hepatology 2014; 29(3), 603-613.
  • Referans48 Leu JI, Crissey MAS, Taub R. Massive hepatic apoptosis associated with TGF-β1 activation after Fas ligand treatment of IGF binding protein-1–deficient mice. The Journal of clinical investigation 2003; 111(1), 129-139.
  • Referans49 Lu B, Xu Y, Xu L, et al. Mechanism investigation of dioscin against CCl4-induced acute liver damage in mice. Environmental toxicology and pharmacology 2012; 34(2), 127-135.
  • Referans50 Xie J, Liu J, Chen TM, et al. Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. World Journal of Gastroenterology: WJG 2015; 21(18), 5473.
  • Referans51 Parajuli DR, Park EJ, Che XH, et al. PF2401-SF, standardized fraction of Salvia miltiorrhiza, induces apoptosis of activated hepatic stellate cells in vitro and in vivo. Molecules 2013; 18(2), 2122-2134.
Toplam 51 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Veteriner Cerrahi
Bölüm Araştırma Makalesi
Yazarlar

Görkem Ekebaş

Ayhan Atasever

Ahmet Alpay Bu kişi benim

Duygu Yaman Gram Bu kişi benim

Yayımlanma Tarihi 30 Aralık 2019
Gönderilme Tarihi 26 Nisan 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 28 Sayı: 3

Kaynak Göster

APA Ekebaş, G., Atasever, A., Alpay, A., Yaman Gram, D. (2019). Ratlarda karbon tetraklorür ile oluşturulan kronik karaciğer hasarı üzerine biberiye ekstraktının (Rosmarinus officinalis) etkisi ve hepatik apoptozisin belirlenmesi. Sağlık Bilimleri Dergisi, 28(3), 110-117. https://doi.org/10.34108/eujhs.558310
AMA Ekebaş G, Atasever A, Alpay A, Yaman Gram D. Ratlarda karbon tetraklorür ile oluşturulan kronik karaciğer hasarı üzerine biberiye ekstraktının (Rosmarinus officinalis) etkisi ve hepatik apoptozisin belirlenmesi. JHS. Aralık 2019;28(3):110-117. doi:10.34108/eujhs.558310
Chicago Ekebaş, Görkem, Ayhan Atasever, Ahmet Alpay, ve Duygu Yaman Gram. “Ratlarda Karbon tetraklorür Ile oluşturulan Kronik karaciğer Hasarı üzerine Biberiye ekstraktının (Rosmarinus Officinalis) Etkisi Ve Hepatik Apoptozisin Belirlenmesi”. Sağlık Bilimleri Dergisi 28, sy. 3 (Aralık 2019): 110-17. https://doi.org/10.34108/eujhs.558310.
EndNote Ekebaş G, Atasever A, Alpay A, Yaman Gram D (01 Aralık 2019) Ratlarda karbon tetraklorür ile oluşturulan kronik karaciğer hasarı üzerine biberiye ekstraktının (Rosmarinus officinalis) etkisi ve hepatik apoptozisin belirlenmesi. Sağlık Bilimleri Dergisi 28 3 110–117.
IEEE G. Ekebaş, A. Atasever, A. Alpay, ve D. Yaman Gram, “Ratlarda karbon tetraklorür ile oluşturulan kronik karaciğer hasarı üzerine biberiye ekstraktının (Rosmarinus officinalis) etkisi ve hepatik apoptozisin belirlenmesi”, JHS, c. 28, sy. 3, ss. 110–117, 2019, doi: 10.34108/eujhs.558310.
ISNAD Ekebaş, Görkem vd. “Ratlarda Karbon tetraklorür Ile oluşturulan Kronik karaciğer Hasarı üzerine Biberiye ekstraktının (Rosmarinus Officinalis) Etkisi Ve Hepatik Apoptozisin Belirlenmesi”. Sağlık Bilimleri Dergisi 28/3 (Aralık 2019), 110-117. https://doi.org/10.34108/eujhs.558310.
JAMA Ekebaş G, Atasever A, Alpay A, Yaman Gram D. Ratlarda karbon tetraklorür ile oluşturulan kronik karaciğer hasarı üzerine biberiye ekstraktının (Rosmarinus officinalis) etkisi ve hepatik apoptozisin belirlenmesi. JHS. 2019;28:110–117.
MLA Ekebaş, Görkem vd. “Ratlarda Karbon tetraklorür Ile oluşturulan Kronik karaciğer Hasarı üzerine Biberiye ekstraktının (Rosmarinus Officinalis) Etkisi Ve Hepatik Apoptozisin Belirlenmesi”. Sağlık Bilimleri Dergisi, c. 28, sy. 3, 2019, ss. 110-7, doi:10.34108/eujhs.558310.
Vancouver Ekebaş G, Atasever A, Alpay A, Yaman Gram D. Ratlarda karbon tetraklorür ile oluşturulan kronik karaciğer hasarı üzerine biberiye ekstraktının (Rosmarinus officinalis) etkisi ve hepatik apoptozisin belirlenmesi. JHS. 2019;28(3):110-7.