HEPATOPROTECTIVE AND HEPATOTHERAPUTIC EFFECTS OF PROPOLIS AGAINST D-GALACTOSAMINE/LIPOPOLYSACCHARIDE-INDUCED LIVER DAMAGE IN RATS

Authors

  • Amer Ramadan Cairo University
  • Gamal Soliman Salman bin Abdulaziz University
  • Sawsan S. Mahmoud National Research Centre
  • Salwa M. Nofal National Research Centre
  • Rehab Fawzy Abdel-rahman Pharmacology Department National Research Centre

Keywords:

Propolis, Galactosamine, Lipopolysaccharide, Hepatotoxicity, Rats

Abstract

Objective: The aim of the present study was to investigate the potential hepatoprotective and hepatotherapeutic activities of propolis against D-galactosamine and lipopolysaccharide (D-GaIN/LPS)-induced hepatotoxicity in rats.

Methods: Hepatotoxicity was induced in rats by intra peritoneal injection of GalN (300 mg/kg) and LPS (30 μg/kg). In the hepatoprotection experiment, propolis was administered orally for 10 days before induction of hepatoxicity. In another experiment (hepatotherapy), propolis was dosed immediately after GalN/LPS injection.

Results: Injection of GalN/LPS to rats induced hepatic damage that was manifested by a significant increase in the activities of aminotransferases, alkaline phosphatase, lactate dehydrogenase and levels of tumor necrosis factor-alpha (TNF-α) and total bilirubin in serum. Liver homogenate of intoxicated animals had the lower content of reduced glutathione with increased levels of the hepatic malondialdehyde and caspase-3 enzyme. Histological data presented marked damage in liver sections of intoxicated rats. Oral dosing of propolis before or once immediately after intoxication reversed these altered parameters near to normal values.

Conclusion: Liver apoptotic events such as DNA fragmentation and increased caspase-3 activity observed during intoxication were prevented by pre and post- propolis treatment. These results suggest that propolis could afford significant protection and therapy in alleviation of hepatotoxicity.

 

Downloads

Download data is not yet available.

References

Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med 2006;354:731-9.

Nakama T, Hirono S, Moriuchi A, Hasuike S, Nagata K, Hori T, et al. Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality. Hepatol 2001;33:1441-50.

Decker K, Keppler D. Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev Physiol Biochem Pharmacol 1974;71:77-106.

Bohlinger I, Leist M, Gantner F, Angermuller S, Tiegs G, Wendel A. DNA fragmentation in mouse organs during endotoxic shock. Am J Pathol 1996;149:1381-93.

Enomoto N, Takei Y, Hirose M, Kitamura T, Ikejima K, Sato N. Protective effect of thalidomide on endotoxin-induced liver injury. Alcohol Clin Exp Res 2003;27:2S-6S.

Tiegs G, Wolter M, Wendel A. Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice. Biochem Pharmacol 1989;38:627-31.

Fantin M, Quintieri L, Kusz E, Kis E, Glavinas H, Floreani M, Padrini R, et al. Pentoxifylline and its major oxidative metabolites exhibit different pharmacological properties. Eur J Pharmacol 2006;535:301-9.

Kara E, CoÅŸkun T, Kaya Y, YumuÅŸ O, Vatansever S, Var A. Effects of silymarin and pentoxifylline on matrix metalloproteinase-1 and-2 expression and apoptosis in experimental hepatic fibrosis. Curr Therap Res 2008;69:488-502.

Velikova M, Bankova V, Tsvetkova I, Kujumgiev A, Marcucci MC. Antibacterial ent-kaurene from Brazilian propolis of native stingless bees. Fitoterapia 2000;71:693-6.

Miyataka H, Nishiki M, Matsumoto H, Fujimoto T, Matsuka M, Satoh T. Evaluation of propolis. I. Evaluation of Brazilian and Chinese propolis by enzymatic and physico-chemical methods. Biol Pharm Bull 1997;20:496-501.

Isla MI, Moreno MIN, Sampietro AR, Vattuone MA. Antioxidant activity of Argentine propolis extracts. J Ethnopharmacol 2001;76:165-70.

Dimov V, Ivanovska N, Manolova N, Bankova V, Nikolov N, Popov S. Immunomodulatory action of propolis. Influence on anti-infectious protection and macrophage function. Apidologie 1991;22:155-62.

Basnet P, Matsushige K, Hase K, Kadota S, Namba T. Four di-O-caffeoyl quinic acid derivatives from propolis. Potent hepatoprotective activity in experimental liver injury models. Biol Pharm Bull 1996;19:1479-84.

Ramadan A, Soliman G, Mahmoud SS, Nofal SM, Abdel-Rahman RF. Evaluation of the safety and antioxidant activities of crocus sativus and propolis ethanolic extracts. J Saudi Chem Soc 2012;16:13-21.

Walker P, Crane E. Constituents propolis. Apidologie 1987;18:327-34.

Lahouel M, Boutabet K, Kebsa W, Alyane M. Polyphenolic fractions of Algerian propolis reverses doxorubicin induced acute renal oxidative stress. Afr J Pharm Pharmacol 2010;4:712-20.

Moreno MI, Isla MI, Sampietro AR, Vattuone MA. Comparison of the free radical-scavenging activity of propolis from several regions of Argentina. J Ethnopharmacol 2000;71:109-14.

Ravikumar V, Shivashangari KS, Devaki T. Hepatoprotective activity of Tridax procumbens against d-galactosamine/lipopolysaccharide-induced hepatitis in rats. J Ethnopharmacol 2005;101:55-60.

New DR, Maggirwar SB, Epstein LG, Dewhurst S, Gelbard HA. HIV-1 Tat induces neuronal death via tumor necrosis factor-alpha and activation of non-N-methyl-D-aspartate receptors by a NFkappaB-independent mechanism. J Biol Chem 1998;273:17852-8.

Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-63.

Kind PR, King EJ. Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine. J Clin Pathol 1954;7:322-6.

Buhl SN, Jackson KY. Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30, and 37 degrees C. Clin Chem 1978;24:828-31.

Doumas BT, Perry BW, Sasse EA, Straumfjord JV. Jr Standardization in bilirubin assays: evaluation of selected methods and stability of bilirubin solutions. Clin Chem 1973;19:984-93.

Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of the biuret reaction. J Biol Chem 1949;177:751-66.

Bartholomew RJ, Delaney AM. Determination of serum albumin. Proc Aust Assoc Clin Biochem 1966;1:214-8.

Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.

Bulaj G, Kortemme T, Goldenberg DP. Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochem 1998;37:8965-72.

Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, de Groot H. Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 1994;59:383-8.

Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001;5:62-71.

Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, et al. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 1997;272:17907-11.

Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.

Burton K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 1956;62:315-23.

Squier MK, Cohen JJ. Standard quantitative assays for apoptosis. Mol Biotechnol 2001;19:305-12.

Krajewska M, Wang HG, Krajewski S, Zapata JM, Shabaik A, Gascoyne R, et al. Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease. Cancer Res 1997;57:1605-13.

Carleton H. Carleton's, Histological Technique, 4th ed. Oxford University Press, New York, Toronto; 1976.

Rasenack J, Koch HK, Nowack J, Lesch R, Decker K. Hepatotoxicity of D-galactosamine in the isolated perfused rat liver. Exp Mol Pathol 1980;32:264-75.

Sallie R, Tredger JM, Williams R. Drugs and the liver. Part 1: Testing liver function. Biopharm Drug Dispos 1991;12:251-9.

Drotman RB, Lawhorn GT. Serum enzymes as indicators of chemically induced liver damage. Drug Chem Toxicol 1978;1:163-71.

Xiong Q, Hase K, Tezuka Y, Namba T, Kadota S. Acteoside inhibits apoptosis in D-galactosamine and lipopolysaccharide-induced liver injury. Life Sci 1999;65:421-30.

Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease, 5th ed. W B Saunders, Philadelphia; 1994.

Poon RT, Yeung C, Liu CL, Lam CM, Yuen WK, Lo CM, et al. Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures: a randomised controlled trial. Gut 2003;52:1768-73.

Macho A, Hirsch T, Marzo I, Marchetti P, Dallaporta B, Susin SA, et al. Glutathione depletion is an early and calcium elevation is a late event of thymocyte apoptosis. J Immunol 1997;158:4612-9.

Ravikumar V, Shivashangari KS, Devaki T. Effect of Tridax procumbens on liver antioxidant defense system during lipopolysaccharide-induced hepatitis in D-galactosamine sensitised rats. Mol Cell Biochem 2005;269:131-6.

Tseng TH, Chu CY, Huang JM, Shiow SJ, Wang CJ. Crocetin protects against oxidative damage in rat primary hepatocytes. Cancer Lett 1995;97:61-7.

Swierkosz TA, Mitchell JA, Warner TD, Botting RM, Vane JR. Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids. Br J Pharmacol 1995;114:1335-42.

Hsu CC, Lin KY, Wang ZH, Lin WL, Yin MC. Preventive effect of Ganoderma amboinense on acetaminophen-induced acute liver injury. Phytomed 2008;15:946-50.

Murphy FR, Issa R, Zhou X, Ratnarajah S, Nagase H, Arthur MJ, et al. Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibito of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis. J Biol Chem 2002;277:11069-76.

Joza N, Kroemer G, Penninger JM. Genetic analysis of the mammalian cell death machinery. Trends Genet 2002:18, 142-9.

Simoes LM, Gregorio LE, Da Silva Filho AA, de Souza ML, Azzolini AE, Bastos JK, et al. Effect of brazilian green propolis on the production of reactive oxygen species by stimulated neutrophils. J Ethnopharmacol 2004;94:59-65.

Gilani AH, Janbaz KH. Preventive and curative effects of Artemisia absinthium on acetaminophen and CCl4-induced hepatotoxicity. Gen Pharmacol 1995;26:309-15.

Published

01-02-2015

How to Cite

Ramadan, A., G. Soliman, S. S. Mahmoud, S. M. Nofal, and R. F. Abdel-rahman. “HEPATOPROTECTIVE AND HEPATOTHERAPUTIC EFFECTS OF PROPOLIS AGAINST D-GALACTOSAMINE/LIPOPOLYSACCHARIDE-INDUCED LIVER DAMAGE IN RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 2, Feb. 2015, pp. 372-8, https://journals.innovareacademics.in/index.php/ijpps/article/view/3925.

Issue

Section

Original Article(s)

Most read articles by the same author(s)