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Farelerde Parasetamol ile İndüklenen Akut Karaciğer Hasarı Üzerine Narın (Punica granatum L.) Etkileri

Year 2016, Volume: 9 Issue: 4, 273 - 280, 01.12.2016

Abstract

Parasetamol toksisitesinin akut karaciğer hasarının en önemli nedeni olduğu rapor edilmiştir. Asetaminofen toksikasyonunda antidot olarak kullanılabilen müstahzarlar bulunmakla birlikte, bazı olgularda bu ilaçlar etkisiz kalabilmektedir. Bu çalışmanın amacı, akut karaciğer hasarı modelinde tam meyve liyofilize Punica granatum L. ekstresinin koruyucu etkinliğini ve yan etkilerini ortaya koymaktır. Çalışmada 80 Swiss Albino fare kullanıldı. Araştırma iki ana grup üzerinde yürütüldü. Yan etki grubundaki farelere 100, 200 ve 400 mg/kg dozunda nar ekstresi verildi. Deneme grubuna ise tek doz parasetamol ile birlikte, eş zamanlı olarak, bahsedilen dozlarda nar ekstresi uygulandı. Biyokimya analiz sonuçları parasetamol ile birlikte verilen liyofilize ekstrenin serum AST, ALT, TP ve TG düzeylerinde önemli oranda bir azalmaya neden olduğunu ortaya koydu. Deneme grubunda verilen nar ekstresi ise RBC, HB, HCT ve LENF konsantrasyonlarında bir düşüşe yol açtı. Histopatoloji analiz sonuçları tek başına verilen ekstrenin hafif-orta derecede karaciğer hasarına yol açabileceğini ortaya koydu. Parasetamol ile birlikte eş zamanlı verilen nar ekstresinin, biyokimya sonuçlarına göre, 200 mg/kg ve histopatoloji sonuçlarına göre ise 400 mg/kg dozlarında karaciğer üzerinde koruyucu etkinliği olabileceği belirlendi. Ölçülen AoA düzeyleri, deneme grubu için, verilen ekstrenin antioksidan aktivitesine vurgu yapmaktadır. Yan etki grubundan elde edilen sonuçlar ise farelerde kullanılan tam meyve liyofilize nar suyu ekstresinin antioksidan aktivite etkisini azaltma eğiliminde olabileceğini gösterdi.

References

  • Alfio B, Anna F, Alessandra O. Paracetamol: New vistas of an old drug. CNS Drug Rev 2006; 12: 250-75.
  • Ashoush IS, El-Batawy OI, El-Shourbagy GA. Antioxidant activity and hepatoprotective effect of pomagranate peel and whey powdersin rats. Ann Agric Sci 2013; 58(1): 27-32.
  • Avlin B, Imaeda AW, Muhammad A, Sohail SM, Mehdi M, Feyyaz S, Sutterwala RA, Flavell WZ. Acetominophen-induced hepatotoxicity in mice is dependent on TIr9 and the Nalp3 inflammasome. J Clin Invest 2009; 119:305-14.
  • Bern M, Sand KMK, Nilsen J, Sandlie I, Andersen JT. The role of albumin receptors in regulation of albumin homeostasis: Implications for drug delivery. J Control Release 2015; 211: 144-62.
  • Bernal W, Juha W, Mohammed R. Use and outcome of liver transplantation in acetaminophen-induced acute liver failure. Hepatology 1998; 27: 1050-55.
  • Black M. Acetaminophen hepatotoxicity. Gastroenterology 1980; 78(2): 382-92.
  • Calignano A, Whittle BJR, Di Rosa M, Moncada S. Involvement of endogenous nitric oxide in the regulation of rat intestinal motility in vivo. Eur J Pharmacol 1992; 229: 273-76.
  • Douidar SM, Boor PJ, Ahmed AE. Potentiation of the hepatotoxic effect of acetaminophen by prior administration of salicylate. J Pharmacol Exp Ther 1985; 233: 242-48.
  • Doyon S, Schwartz WK. Hepatotoxicity despite early administration of intravenous N- acetylcystine for acute acetaminophen overdose. Acad Emerg Med 2009; 16: 34-39.
  • Hajimehdipoor H, Sadeghi Z, Elmi S, Elmi A, Ghazi-Khansari M, Amanzadeh Y. Protective effects of Swertia longifolia Boiss. and its active compound, swerchirin, on paracetamol-induced hepatotoxicity in mice. J Pharm Pharmacol 2006; 58: 277-80.
  • Hinson JA, Reid AB, McCullough SS, James LP. Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab Rev 2004; 36: 805-22.
  • Jain NK, Singhai AK. Protective effects of phyllanthus acidus (L.) skeels leaf extracts on acetaminophen and thioacetamide induced hepatic injuries in wistar rats. Asian Pac J Trop Med 2011; 4: 470.
  • Kanbur M, Eraslan G, Neyaz L, Silici S, Liman BC, Altınordu S, Atasever A. The effects of royal jelly on liver damage induced by paracetamol in mice. Exp Toxc Path 2009; 61: 123-32.
  • Khalil EAM. A hepatoprotective effect of an aqueous extract of pomagranate (Punica granatum L.) rind against acetaminop hen treated rats. EJHM 2004; 16: 112-18.
  • Kittisupamangkol W. Liver injury from diclofenac or acetaminophen? Am J Gastroenterol 2009; 104: 1862.
  • Kupeli E, Orhan DD, Yesilada E. Effect of cistus laurifolius L. leaf extracts and flavanoids on acetaminophen-induced hepatotoxicity in mice. J Ethnopharmacol 2006; 103: 455-60.
  • Larson A. Acetaminophen hepatotoxicity. Clin Liver Dis 2007; 11: 525-48.
  • Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, Du LJ. Evidence of anti-obesty effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond) 2007; 31(6): 1023-29.
  • Lerman LO, De Nigris F, Williams-Ignarro S. Beneficial effects of pomagranate juice on oxidation-sensitive gensand endothelial nitricoxide synthase activity at sites of perturbedshearsstress. Proc Natl Acad Sci 2005; 102: 4896-901.
  • Matthaiou CM, Goutzourelas N, Stagos D, Sarafoglu E, Jamurtas A, Koulocheri SD, Haroutounian SA, Tsatsakis AM, Kouretas D. Pomegranate juice consumption increases GSH levels and reduces lipid and protein oxidation in human blood. Food Chem Toxicol 2014; 73: 1-6.
  • Mazzaccara C, Labruna G, Cito G, Scarfo M, De Felice M, Pastore L, Sacchetti L. Age-Related reference intervals of the main biochemical and hematological parameters in C57BL/6J, 129SV/EV and C3H/HeJ Mouse strains. Plos One 2008; 3(11): 3772.
  • Miguel MG, Neves MA, Antunes MD. Pomagranate (Punica granatum L.) a medicinal plant with myriad biological properties – a short review. J Med Plants Res 2010; 4: 2836-47.
  • Mitchelli JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis, IV. Protective role of glutathione. J Pharmacol Exp Ther 1973; 187: 211-17.
  • Murali A, Ashok P, Madhavan V. Effect of Smilax zeylanica roots and rhizomes in paracetamol induced hepatotoxicity. J Complement Integr Med 2012; 9(1): 1515-53.
  • Nithianantham K, Shyamala M, Chen Y, Latha LY, Jothy SL, Sasidharan S. Hepatoprotective potential of clitoria ternatea leaf extract against paracetamol induced damage in mice. Molecules 2011; 16: 10134-45.
  • Nwanna EE, Oboh G. Antioxidant and hepatoprotective properties of polyphenol exracts from telfairia occidentalis (fluted pumpkin) leaves on acetaminophen induced liver damage. Pak J Biol Sci 2007; 10: 2682-87.
  • Oshida K, Iwanaga E, Miyamato-Kuramitsu K, Miyamato Y. An in vivo comet assay of multiple organs (liver, kidney and bone marrow) in mice treated with methyl methanesulfonate and acetaminophen accompanied by hematology and/or blood chemistry. J Toxicol Sci 2008; 33(5): 515-24.
  • Osman M, Ahmed M, Mahfouz S, Elaby S. Biochemical studies on the hepatoprotective effects of pomegranate and guava ethanol extracts. NY Sci J 2011; 4(3): 27-41.
  • Patel C, Dadhaniya P, Hingorani L, Soni MG. Safety assessment of pomegranate fruit extract: Acute and subchronic toxicity studies. Food Chem Toxicol 2008; 46: 2728-35.
  • Ranganathan SS, Sathiadas MG, Sumanasena S, Fernandopulle M, Lamabadusuriya SP, Fernandopulle BM. Fulminant hepatic failure and paracetamol overuse with therapeutic intent in febrile children. Indian J Pediatr 2006; 73(10): 871-75.

Effects of Pomegranate (Punica granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice

Year 2016, Volume: 9 Issue: 4, 273 - 280, 01.12.2016

Abstract

The most common cause of acute liver failure has been reported as paracetamol toxicity. There are some drugs that can be used as an antidote for acetaminophen toxicity, but in some cases these drugs are ineffective. The purpose of this study is to identify protective and side effects of lyophilized extract’s from Punica granatum L. in acute liver injury model. In our study, 80 Swiss Albino mice were used. The research was conducted on two main groups. The mice in the side effect group were given pomegranate extracts at 100, 200 and 400 mg/kg doses. The trial group were administered mentioned doses of extracts and a single dose of paracetamol simultaneously. The results gained from biochemistry analysis demonstrated that lyophilized extract given along with paracetamol caused a significant decrease in serum AST, ALT, TP and TG levels. The pomegranate extract given to the experiment group led to a decrease in RBC, HB, HCT and LYMP levels. Histopathological evaluation demonstrated that the extract alone may cause liver injury ranging from mild to moderate. Yet the extract given simultaneously with paracetamol particularly may have a protective effect on liver in a certain dose of 200 mg/kg according to biochemistry results and in a certain dose of 400 mg/kg according to histopathological analysis. Measured AoA levels emphasize the antioxidant activity of the extract for trial group. The results obtained from the side effect group have emphasized possible reducing effect of antioxidant activity of lyophilized extract in mice.

References

  • Alfio B, Anna F, Alessandra O. Paracetamol: New vistas of an old drug. CNS Drug Rev 2006; 12: 250-75.
  • Ashoush IS, El-Batawy OI, El-Shourbagy GA. Antioxidant activity and hepatoprotective effect of pomagranate peel and whey powdersin rats. Ann Agric Sci 2013; 58(1): 27-32.
  • Avlin B, Imaeda AW, Muhammad A, Sohail SM, Mehdi M, Feyyaz S, Sutterwala RA, Flavell WZ. Acetominophen-induced hepatotoxicity in mice is dependent on TIr9 and the Nalp3 inflammasome. J Clin Invest 2009; 119:305-14.
  • Bern M, Sand KMK, Nilsen J, Sandlie I, Andersen JT. The role of albumin receptors in regulation of albumin homeostasis: Implications for drug delivery. J Control Release 2015; 211: 144-62.
  • Bernal W, Juha W, Mohammed R. Use and outcome of liver transplantation in acetaminophen-induced acute liver failure. Hepatology 1998; 27: 1050-55.
  • Black M. Acetaminophen hepatotoxicity. Gastroenterology 1980; 78(2): 382-92.
  • Calignano A, Whittle BJR, Di Rosa M, Moncada S. Involvement of endogenous nitric oxide in the regulation of rat intestinal motility in vivo. Eur J Pharmacol 1992; 229: 273-76.
  • Douidar SM, Boor PJ, Ahmed AE. Potentiation of the hepatotoxic effect of acetaminophen by prior administration of salicylate. J Pharmacol Exp Ther 1985; 233: 242-48.
  • Doyon S, Schwartz WK. Hepatotoxicity despite early administration of intravenous N- acetylcystine for acute acetaminophen overdose. Acad Emerg Med 2009; 16: 34-39.
  • Hajimehdipoor H, Sadeghi Z, Elmi S, Elmi A, Ghazi-Khansari M, Amanzadeh Y. Protective effects of Swertia longifolia Boiss. and its active compound, swerchirin, on paracetamol-induced hepatotoxicity in mice. J Pharm Pharmacol 2006; 58: 277-80.
  • Hinson JA, Reid AB, McCullough SS, James LP. Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab Rev 2004; 36: 805-22.
  • Jain NK, Singhai AK. Protective effects of phyllanthus acidus (L.) skeels leaf extracts on acetaminophen and thioacetamide induced hepatic injuries in wistar rats. Asian Pac J Trop Med 2011; 4: 470.
  • Kanbur M, Eraslan G, Neyaz L, Silici S, Liman BC, Altınordu S, Atasever A. The effects of royal jelly on liver damage induced by paracetamol in mice. Exp Toxc Path 2009; 61: 123-32.
  • Khalil EAM. A hepatoprotective effect of an aqueous extract of pomagranate (Punica granatum L.) rind against acetaminop hen treated rats. EJHM 2004; 16: 112-18.
  • Kittisupamangkol W. Liver injury from diclofenac or acetaminophen? Am J Gastroenterol 2009; 104: 1862.
  • Kupeli E, Orhan DD, Yesilada E. Effect of cistus laurifolius L. leaf extracts and flavanoids on acetaminophen-induced hepatotoxicity in mice. J Ethnopharmacol 2006; 103: 455-60.
  • Larson A. Acetaminophen hepatotoxicity. Clin Liver Dis 2007; 11: 525-48.
  • Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, Du LJ. Evidence of anti-obesty effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond) 2007; 31(6): 1023-29.
  • Lerman LO, De Nigris F, Williams-Ignarro S. Beneficial effects of pomagranate juice on oxidation-sensitive gensand endothelial nitricoxide synthase activity at sites of perturbedshearsstress. Proc Natl Acad Sci 2005; 102: 4896-901.
  • Matthaiou CM, Goutzourelas N, Stagos D, Sarafoglu E, Jamurtas A, Koulocheri SD, Haroutounian SA, Tsatsakis AM, Kouretas D. Pomegranate juice consumption increases GSH levels and reduces lipid and protein oxidation in human blood. Food Chem Toxicol 2014; 73: 1-6.
  • Mazzaccara C, Labruna G, Cito G, Scarfo M, De Felice M, Pastore L, Sacchetti L. Age-Related reference intervals of the main biochemical and hematological parameters in C57BL/6J, 129SV/EV and C3H/HeJ Mouse strains. Plos One 2008; 3(11): 3772.
  • Miguel MG, Neves MA, Antunes MD. Pomagranate (Punica granatum L.) a medicinal plant with myriad biological properties – a short review. J Med Plants Res 2010; 4: 2836-47.
  • Mitchelli JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis, IV. Protective role of glutathione. J Pharmacol Exp Ther 1973; 187: 211-17.
  • Murali A, Ashok P, Madhavan V. Effect of Smilax zeylanica roots and rhizomes in paracetamol induced hepatotoxicity. J Complement Integr Med 2012; 9(1): 1515-53.
  • Nithianantham K, Shyamala M, Chen Y, Latha LY, Jothy SL, Sasidharan S. Hepatoprotective potential of clitoria ternatea leaf extract against paracetamol induced damage in mice. Molecules 2011; 16: 10134-45.
  • Nwanna EE, Oboh G. Antioxidant and hepatoprotective properties of polyphenol exracts from telfairia occidentalis (fluted pumpkin) leaves on acetaminophen induced liver damage. Pak J Biol Sci 2007; 10: 2682-87.
  • Oshida K, Iwanaga E, Miyamato-Kuramitsu K, Miyamato Y. An in vivo comet assay of multiple organs (liver, kidney and bone marrow) in mice treated with methyl methanesulfonate and acetaminophen accompanied by hematology and/or blood chemistry. J Toxicol Sci 2008; 33(5): 515-24.
  • Osman M, Ahmed M, Mahfouz S, Elaby S. Biochemical studies on the hepatoprotective effects of pomegranate and guava ethanol extracts. NY Sci J 2011; 4(3): 27-41.
  • Patel C, Dadhaniya P, Hingorani L, Soni MG. Safety assessment of pomegranate fruit extract: Acute and subchronic toxicity studies. Food Chem Toxicol 2008; 46: 2728-35.
  • Ranganathan SS, Sathiadas MG, Sumanasena S, Fernandopulle M, Lamabadusuriya SP, Fernandopulle BM. Fulminant hepatic failure and paracetamol overuse with therapeutic intent in febrile children. Indian J Pediatr 2006; 73(10): 871-75.
There are 30 citations in total.

Details

Journal Section RESEARCH ARTICLE
Authors

Mehmet Ali Erfidan This is me

Esra Küpeli Akkol This is me

Alper Sevimli This is me

Turan Civelek

Publication Date December 1, 2016
Acceptance Date October 18, 2016
Published in Issue Year 2016 Volume: 9 Issue: 4

Cite

APA Erfidan, M. A., Küpeli Akkol, E., Sevimli, A., Civelek, T. (2016). Effects of Pomegranate (Punica granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice. Kocatepe Veterinary Journal, 9(4), 273-280.
AMA Erfidan MA, Küpeli Akkol E, Sevimli A, Civelek T. Effects of Pomegranate (Punica granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice. kvj. December 2016;9(4):273-280.
Chicago Erfidan, Mehmet Ali, Esra Küpeli Akkol, Alper Sevimli, and Turan Civelek. “Effects of Pomegranate (Punica Granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice”. Kocatepe Veterinary Journal 9, no. 4 (December 2016): 273-80.
EndNote Erfidan MA, Küpeli Akkol E, Sevimli A, Civelek T (December 1, 2016) Effects of Pomegranate (Punica granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice. Kocatepe Veterinary Journal 9 4 273–280.
IEEE M. A. Erfidan, E. Küpeli Akkol, A. Sevimli, and T. Civelek, “Effects of Pomegranate (Punica granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice”, kvj, vol. 9, no. 4, pp. 273–280, 2016.
ISNAD Erfidan, Mehmet Ali et al. “Effects of Pomegranate (Punica Granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice”. Kocatepe Veterinary Journal 9/4 (December 2016), 273-280.
JAMA Erfidan MA, Küpeli Akkol E, Sevimli A, Civelek T. Effects of Pomegranate (Punica granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice. kvj. 2016;9:273–280.
MLA Erfidan, Mehmet Ali et al. “Effects of Pomegranate (Punica Granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice”. Kocatepe Veterinary Journal, vol. 9, no. 4, 2016, pp. 273-80.
Vancouver Erfidan MA, Küpeli Akkol E, Sevimli A, Civelek T. Effects of Pomegranate (Punica granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice. kvj. 2016;9(4):273-80.

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