Hepatoprotective activity of phloretin and hydroxychalcones against Acetaminophen Induced hepatotoxicity in mice
Iranian Journal of Pharmaceutical Sciences,
Vol. 7 No. 2 (2011),
1 Farvardin 2011
,
Page 89-97
https://doi.org/10.22037/ijps.v7.41330
Abstract
Polyphenolics form a major part of the dietary antioxidant capacity of fruits and vegetables have been identified as chemopreventive or anticancer agents. Hydroxychalcones are polyphenols abundantly distributed throughout the plant kingdom and are compounds with two aromatic rings (benzene or phenol) and an unsaturated side chain. In the present study, effect of phloretin (apple major flavonoid), 4-hydroxychalcone and 4'-hydroxychalcone were investigated against acetaminophen-induced acute liver damage. The study was designed as multiple dose pre- and post-treatments. Mice were administrated
acetaminophen (1g/kg and 640 mg/kg for mortality and acute toxicity experiments, respectively). Mortality rate, serum transaminases (SGOT and SGPT) and histological examination were applied. Acetaminophen produced 100% mortality at the dose of 1 g/kg in mice, while pre-treatment and post-treatment (i.p., twice daily for 48 hrs) of animals with phloretin and 4-hydroxychalcone (50 mg/kg) and 4'-hydroxychalcone (25 mg/kg) significantly reduced the mortality rate. Acetaminophen produced acute toxicity at the dose of 640 mg/kg in mice, while pre- and post-treatments of animals with phloretin and hydroxychalcones significantly lowered the rise in SGOT and SGPT. Liver sections collected for histological examination showed cellular changes including centrilobular necrosis, extensive portal inflammation, and micro and macro vesicular structures in the acetaminophen group. These cellular changes were reduced following treatment of mice with Phloretin and hydroxychalcones. Taken collectively, from the results of this study it may be suggested that phloretin and hydroxychalcones have hepatoprotective activity against acetaminophen liver injury in mice.
- Phloretin,
- Hydroxychalcones,
- Hepatoprotection,
- Acetaminophen,
- SGOT,
- SGPT
How to Cite
References
[2] Dhar DN. The chemistry of chalcones and related compounds. New York: Wiley, 1981.
[3] Tomas–Barberan FA, Clifford MN. Flavones, chalcones and dihydrochalcones–nature occurrence and dietary burden. J Sci Food Agric 2000; 80: 1073–80.
[4] Hsieh HK, Tsao LT, Wang JP, Lin CN. Synthesis and anti-inflammatory effect of chalcones. J Pharm Pharmacol 2000; 52: 163–71.
[5] Satyanarayana K, Rao MNA. Antiinflammatory, analgesic and antipyretic activities of 3-(4-(3-(4-dimeThylaminophenyl)–1-oxo-2–propenyl) phenyl sydnone. Indian Drugs 1993; 30: 313-18.
[6] Ballesteros JF, Sanz MJ, Ubeda A, Miranda MA, Iborra S, Paya M, Alcaraz MJ. Synthesis and pharmacological evaluation of 2'-hydroxy chalcones and flavones as inhibitors of inflammatory medicators generation. J Med Chem 1995; 38: 2794–7.
[7] Hsieh HK, Tsao LT, Wang JP, Lin CN. Synthesis and anti-inflammatory effect of chalcones. J Pharm Pharmacol 2000; 52 163-71.
[8] Hilt P, Schieber A, Yildirim C, Arnold G, Klaiber I, Conrad J, Beifuss U, Carle R. Detection of phloridzin in strawberries (Fragaria x ananassa Duch.) by HPLC-PDA-MS/MS and NMR spectroscopy. J Agric Food Chem 2003; 51: 2896-2899.
[9] Vale JA. Paracetamol poisoning. Lancet 1995; 346: 547–52.
[10] Crppin JC. Acetaminophen Hepatotoxicity potentiation by isoniazid. Am J Gastroenterol 1993; 88: 590–2.
[11] Minton N, Heny J, Frankel R. Fatal paracetamol poisoning epidemic. Hum Toxicol 1988; 7: 33 –4.
[12] Moling O, Cairon E, Rimenti G, Rizzi F, Pristira R, Mian P. Sever hepatotoxicity after therapeutic doses of acetaminophen. Clin Therapy 2006; 28: 755-60.
[13] Dahlin DC, Miwa GT, Lu AYH, Nelson SD. Nacetyl-p-benzoquinone imine: A cytochrome P-450-mediated oxidation product of acetaminophen. Proc Nati Acad Sci 1984; 81:1327-31.
[14] Zhang Q, Melnikov Z, Feierman DE. Characterization of the acetaminophen-induced degradation of cytochrome p450-3A4 and the proteolytic pathway. Basic & Clin Pharmacol & Toxicol 2004; 94: 191-200.
[15] Chen YH, Lin FY, Liu PL, Huang YT, Chiu JH, Chang YC, Man KM, Hong CY, Ho YY, Lai MT. Antioxidative and hepatoprotective effects of Magnolol on acetaminophen-induced liver damage in rats. Arch Pharm Res 2009; 32: 221-28.
[16] Kanter MZ. Comparison of oral and i.v.acetylcysteine in the treatment of acetaminophen poisoning. Am J Health-Syst Pharm 2006; 63:1821-27.
[17] Escarpa A, González MC. High-performance liquid chromatography with diode-array detection for the determination of phenolic compounds in peel and pulp from different apple varieties. J Chromatogr 1998; A823: 331-7.
[18] Tsao R, Yang R, Young JC, Zhu H. Polyphenolic profiles in eight apple cultivars using highperformance liquid chromatography (HPLC). J Agric Food Chem 2003; 51: 6347-53.
[19] Xiao C, Cant JP. Glucose transporter in bovine mammary epithelial cells is an asymmetric carrier that exhibits cooperativity and trans-stimulation. Am J Physiol Cell Physiol 2003; 285: C1226-C1234.
[20] Raja MM, Tyagi NK, Kinne, RKH. Phlorizin recognition in a C-terminal fragment of SGLT1studied by tryptophan scanning and affinity labeling. J Biol Chem 2003; 278: 49154-4963.
[21] Rezk BM, Haenen GRMM, Vander Vijgh WJF, Bast A. The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids. Biochem Biophys Res Commun 2002; 295: 9-13.
[22] Nakamura Y, Watanabe S, Miyake N, Kohno H, Osawa T. Dihydrochalcones: evaluation as novel radical scavenging antioxidants. J Agric Food Chem 2003; 51: 3309-12.
[23] Stangl V, Lorenz M, Ludwig A, Grimbo N, Guether C, Sanad W, Ziemer S, Martus P, Baumann G, Stangl K. The flavonoid phloretin suppresses stimulated expression of endothelial adhesion molecules and reduces activation of human platelets. J Nutr 2005; 135: 172-8.
[24] Lewis JH, Ahmed M, Shobassy A, Palese C.Drug induced liver disease. Curr Opin Gastroenterol 2006; 22: 223-33.
[25] Porchezhian E, Ansari SH. Hepatoprotective activity of Abutilon indicum on experimental liver damage in rats. Phytomedicine. 2005; 12:62–4.
[26] Nelson SD. Molecular mechanisms of the hepatotoxicity caused by Acetaminophen. Semin Liver Dis 1990; 10: 267–78.
[27] William RT. Detoxification Mechanisms. New York, USA: John Willey, 1971.
[28] Kew MC. Serum aminotransferase concentration as evidence of hepato cellular damage. Lancet 2000; 355: 591-592.
[29] Beumer JH, Schellens JHM, Beijnen JH.Hepatotoxicity and metabolism of trabectedin: a literature review. Pharmacol Res 2005; 51: 391-8.
[30] Yemitan OK, Izegbu MC. Protective effects of Zingiber officinale (Zingiberaceae) against Carbon Tetrachloride and acetaminophen-induced hepatotoxicity in rats. Phytother Res 2006; 20: 997-1002.
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