Protective Effects of Amburoside A, a Phenol Glucoside from Amburana cearensis, against CCl₄-Induced Hepatotoxicity in Rats

Abstract

The aim of this study was to investigate the possible beneficial effects of amburoside A, AMB [4-(O-β-D-glycopyranosyl)benzyl protocatechoate], against carbon tetrachloride (CCl₄) toxicity in rats. AMB is a phenol glucoside from the Brazilian medicinal plant Amburana cearensis, popularly used for the treatment of respiratory tract affections. Acute AMB (25 and 50 mg/kg, i. p. or p. o.) treatments of CCl₄-intoxicated rats significantly inhibited the increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as compared to the group treated with CCl₄ only. Histological studies showed less centrolobular necrosis and inflammatory cell infiltrates in the liver of animals treated with AMB plus CCl₄, when compared to the group treated with CCl₄ alone. In hepatic tissues, AMB at both doses inhibited CCl₄-induced thiobarbituric acid-reactive substances (TBARS) formation, indicating a blockade of CCl₄-induced lipid peroxidation. AMB also reversed the decrement in glutathione contents of hepatic tissues in CCl₄-intoxicated rats. Furthermore, it restored catalase activity to normal values, which was significantly increased after CCl₄ treatment. Our results indicate that CCl₄-induced oxidative damage in hepatic tissues is reversed by AMB treatment. The protective effect of AMB is probably due to the phenolic nature of this glucoside.

Key words

Amburoside A - Amburana cearensis - Fabaceae - hepatoprotective activity - carbon tetrachloride toxicity

References

• 1 Meyer S A, Kulkarni A P. Hepatotoxicity. In: Hodgson E, Smart RC, editors. Introduction to biochemical toxicology, 3 rd edition. New York; John Wiley & Sons 2001
• 2 Poli G. Liver damage due to free radicals.  Br Med Bull. 1993;  49 604-20
• 3 Recknagel R O, Glende Jr E A, Dolak J A, Waller R L. Mechanisms of carbon tetrachloride toxicity.  Pharmacol Ther. 1989;  43 139-54
• 4 Handa S S, Sharma A, Chakraborti K K. Natural products and plants as liver protecting drugs.  Fitoterapia. 1986;  57 307-45
• 5 Hsu C -Y. Antioxidant activity of extract from Polygonum aviculare L.  Biol Res. 2006;  39 281-8
• 6 Braga R. Plantas do Nordeste especialmente do Ceará, 3 rd Edition. Fortaleza; Imprensa Oficial 1976: 219
• 7 Canuto K M, Silveira E R. Constituintes químicos da casca do caule de Amburana cearensis A. C. Smith.  Quim Nova. 2006;  29 1241-3
• 8 Bravo B, Sauvain M. Bioactive phenolic glycosides from Amburana cearensis.  Phytochemistry. 1999;  50 71-4
• 9 Leal L KAM, Nechio M, Silveira E R, Canuto K M, Fontenele R A, Viana G SB. Anti-inflammatory and smooth muscle relaxant activities of the hydroalcoholic extract and chemical constituents from Amburana cearensis A. C. Smith.  Phytother Res. 2003;  17 335-40
• 10 Leal L KAM, Costa M F, Pitombeira M, Silveira E R, Canuto K M, Viana G S. Mechanisms underlying the relaxation induced by isokaempferide from Amburana cearensis in the guinea-pig isolated trachea.  Life Sci. 2006;  79 98-104
• 11 Costa-Lotufo L V, Jimenez P C, Wilke D V, Leal L KAM, Silveira E R, Viana G SB. Antiproliferative effects of several compounds isolated from Amburana cearensis A.C.Smith.  Z Naturforsch [C]. 2003;  58 675-80
• 12 Leal L KAM, Moraes M O, Pessoa C, Silveira E R, Canuto K M, Viana G SB. Amburoside A, a glucoside from Amburana cearensis, protects mesencephalic cells against 6-hydroxydopamine-induced neurotoxicity.  Neurosci Lett. 2005;  388 86-90
• 13 Buege J A, Aust S D. Microsomal lipid peroxidation.  Methods Enzymol. 1978;  52 302-10
• 14 Ellman G L. Tissue sulfhydryl group.  Arch Biochem Biophys. 1959;  82 70-7
• 15 Lowry O H, Rosebrough A L, Randall R J. Protein measurement with folin phenol reagent.  Biol Chem. 1951;  193 265-71
• 16 Aebi H. Catalase in vitro.  Methods Enzymol. 1974;  2 673-8
• 17 Ha J B, Lee J Y. The effect of chondroitin sulfate against CCl₄-induced hepatotoxicity.  Biol Pharm Bull. 2003;  26 622-6
• 18 Arora A, Byrem T M, Nair M G, Strasburg G M. Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids.  Arch Biochem Biophys. 2000;  373 102-9
• 19 Panda S, Kar A. Apigenin (4′,5,7-trihydroxyflavone) regulates hyperglycaemia, thyroid dysfunction and lipid peroxidation in alloxan-induced diabetic mice.  J Pharm Pharmacol. 2007;  59 543-8
• 20 Cabre M, Comps J, Paternain J L, Ferre N, Joven J. Time course of changes in hepatic lipid peroxidation and glutothione metabolism in rats with carbon tetrachloride-induced cirrhosis.  Clin Exp Pharmacol Physiol. 2000;  27 694-9
• 21 Edwards M J, Keller B J, Kauffman F C, Thurman R G. The involvement of Kupffer cells in carbon tetrachloride toxicity.  Toxicol Appl Pharmacol. 1993;  119 275-9
• 22 Shigeki A, Masayuki I. Physiological role of sinusoidal endothelial cells and Kupffer cells and their implication in pathogenesis of liver injury.  J Hepatobiliary Pancreat Surg. 1999;  7 40-8
• 23 Proctor P H, McGinness J E. The function of melanin.  Arch Dermatol. 1986;  122 507-8
• 24 Rohrdanz E, Kahl R. Alterations of antioxidant enzyme expression in response to hydrogen peroxide.  Free Radic Biol Med. 1998;  24 27-38
• 25 Szymonik-Lesiuk S, Czechowska G, Stryjecka-Zimmer M, Slomka M, Madro A, Celinski K. et al . Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication.  J Hepatobiliary Pancreat Surg. 2003;  10 309-15
• 26 Shull S, Heintz N H, Periasamy M, Mamokor M, Jansen Y MW, Marsh I P. et al . Differential regulation of antioxidant enzymes in response to oxidants.  J Biol Chem. 1991;  266 24 398-403
• 27 Rahman I, Biswas S K, Jimenez L A, Torres M, Forman H J. Glutathione, stress responses, and redox signaling in lung inflammation.  ARS. 2005;  7 42-59
• 28 Galato D, Ckless K, Susin M F, Giacomelli C, Ribeiro-do-Valle R M, Spin A. Antioxidant capacity of phenolic and related compounds: correlation among electrochemical, visible spectroscopy methods and structure-antioxidant activity.  Redox Rep. 2001;  6 243-50
• 29 Zhao Z S, O’Brien P J. The prevention of CCl₄-induced liver necrosis in mice by naturally occurring methylenedioxybenzenes.  Toxicol Appl Pharmacol. 1996;  140 411-21
• 30 Mohamed M A, Marzouk M S, Moharram F A, El-Sayed M M, Baiuomy A R. Phytochemical constituents and hepatoprotective activity of Viburnum tinus.  Phytochemistry. 2005;  66 2780-6