Parasetamol İndüklü Hepatotoksisite Modelinde Kafeik Asit Fenil Ester’ in İnflamasyon ve Oksidatif Stres Üzerine Etkisinin Araştırılması

Yıl 2019, Cilt: 14 Sayı: 3, 290 - 298, 25.12.2019

Nuket Kamiş Funda Karabağ

https://doi.org/10.17094/ataunivbd.552207

Cited By: 1

Öz

Parasetamol ucuz olması, kolay bulunabilmesi bakımından sık kullanılan ağrı kesici, ateş düşürücü etkisi olan bir ilaçtır. Parasetamol, karaciğerde metabolize olmaktadır. Yüksek dozda parasetamol karaciğer hasarına (hepatotoksisite) neden olmaktadır. Kafeik Asit Fenil Ester (CAPE); antimikrobik, antiinflamatuvar ve antioksidan özelliklere sahip bir bileşendir. Uzun aromatik ve alifatik yapıdaki karbonları olmasından dolayı hücre duvarından kolayca geçer ve etki edeceği bölgeye daha rahat ulaşır. Bu çalışmanın amacı ratlara parasetamol ile hepatotoksisite oluşturulup meydana gelebilecek oksidatif stres ve enflamasyon üzerine CAPE’nin koruyucu etkisini araştırmak için tasarlanmıştır. Sunulan çalışmada, 36 wistar erkek rat kullanıldı. Rastgele olacak şekilde altı gruba ayrıldı; kontrol grubu; sadece yem verildi, parasetamol grubu; 2 g/kg parasetamol, parasetamol+CAPE grubu; 2 g/kg parasetamol+ 10 μg/kg CAPE, parasetamol+NAC grubu; parasetamol 2 g/kg + NAC (140 mg/kg) ve 140 mg/kg N-Asetilsistein 1 saat sonrasında da 2g/kg dozunda, 2 ml parasetamol, CAPE grubu; 10 mikrogram/kg CAPE ve etanol grubu; CAPE’nin çözdürüldüğü oranda seyreltik etenol. Veriler istatistiksel olarak SPSS-18 ANOVA ile standart sapma olarak değerlendirilmiştir. P<0.05 anlamlı olarak kabul edilmiştir. Çalışmanın sonucunda, parasetamol indüklü hepatotoksisite modelinde kontrol grubuna göre parasetamol grubunda oksidatif stres parametrelerinin ve sitokin seviyelerinin istatistiksel olarak arttığı (P<0.05), CAPE verilen grupla parasetamol grubu karşılaştırıldığında, CAPE’nin meydana gelen enflamasyon ve oksidatif strese karşı koruyucu bir etki gösterdiği gözlemlenmiştir.

Anahtar Kelimeler

CAPE, Hepatotoksisite, Oksidatif stres, Parasetamol, Rat

Investigation of Caffeic Acid Phenethly Ester Effect on Inflammation and Oxidative Stress in Paracetamol Induced Hepatotoxicity

Öz

Paracetamol is a cheap, pain-relieving, fever-reducing medicine that can be easily found. Paracetamol is metabolized in the liver. At high doses, paracetamol causes liver damage hich is called hepatotoxicity. Caffeic Acid Phenyl Ester (CAPE) has antimicrobial, anti-inflammatory and antioxidant properties. Due to its long aromatic and aliphatic carbon structure, it passes easily through the cell wall and reaches the region where it will act more easily. The aim of this study is to understand the CAPE protective effect to hepatoxisitiy oxidative stress and inflamation during the application of paracetamol. In tis study 36 wistar rat was used and they were divided into six groups randomly. Control: given only forage. Paracetamol; 2 g/kg döşe of paracetamol. Paracetamol +CAPE; 2 g/kg döşe of paracetamol + 10 ug/kg CAPE. Paracematol + NAC; Paracetamol 2 g/kg + NAC (140 mg/kg); 140 mg/kg N-asetil Sistein applied after one hour 2 g/kg dose of 2 ml paracetamol. CAPE:10 microgram/kg CAPE and ethanol group. The data is analyzed statistically SpSS-18 ANOVA standard variaton. P<0.05 is accepted meaningful. According to the results obtained, it is seen that hepatoxisity induced paracetamol model has more oxidative stress statistically than the control group (P<0.05). The groups which were given CAPE and paracetamol group when compared, CAPE has protective effect to the occuring inflamation.

Anahtar Kelimeler

CAPE, Hepatotoxicity, Oxidative stres, Paracetamol, Rat

Kaynakça

• 1. Emet M., 2016. Asetaminofen (Parasetamol) Zehirlenmesi. Türkiye Klin J Emerg Med Top, 2, 51-57. 2. Jack A., Hinson Dean W., Roberts Laura P., 2010. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol, 196, 369-405. 3. Mohammed A., Almansori Hassan I., Alhammadi Fahad A., 2015. Paracetamol overdose: Analysis of a sample from a tertiary hospital in Eastern Saudi Arabia. Saudi J Med Sci, 3, 209-212. 4. Licata A., 2016. Adverse drug reactions and organ damage: The liver. Eur J Intern Med, 28, 9-16. 5. Hepşen F., Tdlgen F., Er H., 1996. Propolis: Tıbbi özellikleri ve oftalmolojik kullanımı. Turgut Özal Tıp Merkezi Dergisi, 3, 386-391. 6. Azza H., Sobhy E., Asmaa E., Ahmed A., 2016. Effect of bee venom or proplis on molecular and parasitological aspects of Schistosoma mansoni infected mice. J Parasit Dis, 40, 390-400. 7. Ümit G., Cihan T., Izzet S., Bugra C., Mustafa O., Tayfun G., Engin D., 2017. Protective effect of caffeic acid phenethyl ester (CAPE) on ischemia–reperfusion injury in rat ovary. Int J Morphol, 35, 141-147. 8. Laura C., Marco B., Jianbo X., Bruno B., 2017. Therapeutic properties of bioactive compounds from different honeybee products. Front Pharmacol, 8, 412-419. 9. Uzkeser M., Karakus E., Albayrak A., Kiki İ., Bayir Y., Cadirci E., Unal D., Halici Z., Karadeniz A., 2012. Protective effect of panax ginseng against N-acetyl-pamino¬phenol-induced hepatotoxicity in rats. Afr J Pharm, 6, 2634-2642. 10. Sushıl JK., 1986. Membran lipid peroxidation in erythrocytes of the newborn. Cli Chi Acta, 161, 301-306. 11. Mun Chiang C., James P., 2016. Pharmacological targeting of the HIF hydroxylases – a new field in medicine development. Mol Aspects Med, 47, 54-75. 12. Halliwell B., 2007. Biochemistry of oxidative stress. Biochem Soc Trans, 35, 1147-1150. 13. Douıdar SM., Boor PJ., Ahmed AE., 1985. Potentiation of the hepatotoxic effect of acetaminophen by prior administration of salicylate. J Pharmaco Exp Ther, 233, 242-248. 14. Mohammed M., Gulrana K., Mohammad F., Sohail H., Mohammad AS, 2016. Cadmium-induced nephrotoxicity via oxidative stress in male Wistar rats and capsaicin protects its toxicity. Bull Env Pharmacol Life Sci, 5, 05-11. 15. Hoi-Shan W., Pratiksha A., Vojtech M., Pierre-Axel M., Martin D., 2017. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem, 292, 16804-16809. 16. Parmar SR., Vashrambhai PH., Kalia K., 2010. Hepatoprotective activity of some plants extract against paracetamol induced hepatotoxicity in rats. J Herb Med, 4, 101-106. 17. Naguib YM., Azmy RM., Samaka RM., Salem MF., 2014. Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress in acetaminophen-induced hepato-renal injury. BMC Complement Altern Med, 14, 494. 18. Domitrovic R., Jakovac H., Rahelic D., Romic Z., Tadic Z., 2010. Antifibrotic activity of taraxacum officinale root in carbon tetrachloride-induced liver damage in mice. J Ethnopharmacol, 130, 569-577. 19. Malhi H., Gores GJ., Lemasters JJ., 2006. Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology, 43, 31-44. 20. Yuan Mohamed A., Richard D., Salminen L., Mendrick Y., 2017. Proteomic analysis of acetaminophen‐induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury. Proteomics Clin Appl, 11, 1600123. 21. Chularojmontri L, Wattanapitayakul SK., Herunsalee A., Charuchongkolwongse S., Niumsakul S., Srichairat S., 2005. Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on doxorubicin-induced cardiotoxicity. Biol Pharm Bull, 28, 1165-1171. 22. Luster MI., Simeonova PP., Gallucci RM., Bruccoleri A., Blazka ME., Yucesoy B., Matheson JM., 2009. The role of tumor necrosis factor alpha in chemical-induced hepatotoxicity. Ann N Y Acad Sci, 919, 214-20. 23. Teng CY., Lai YL., Huang HI., Hsu WH., Yang CC., Kuo WH., 2012. Tournefortia sarmentosa extract attenuates acetaminophen-induced hepatotoxicity. Pharm Biol, 50, 291-396. 24. Wu YL., Jiang YZ., Jin XJ., Lian LH., Piao JY., Wan Y, Jin HR., Joon Lee J., Nan JX., 2010. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice. Phytomedicine, 17, 475-479. 25. Yan SL, Wu ST, Yin MC, Chen HT, Chen HC. 2009. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. Journal of food science, 74, 259-260. 26. Wu YL., Jiang YZ., Jin XJ., Lian LH., Piao JY., Wan Y., Jin HR., Joon LJ., Nan JX., 2010. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminopheninduced hepatic toxicity in mice. Phytomedicine, 17, 475-479.