Abstract
The intestinal anti-inflammatory activity of several doses of silymarin was tested in the acute stage of the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. The results obtained show that oral pre-treatment with 50 mg/kg of silymarin significantly attenuated macroscopic colonic damage as well as reduced colonic myeloperoxidase activity compared to non-treated colitic animals. The beneficial effect was accompanied by an improvement in the colonic oxidative status, which was altered in colonic inflammation, by preventing glutathione depletion and reducing malonyldialdehyde production. This suggests that the well known antioxidant properties of silymarin can participate in its intestinal anti-inflammatory activity. In addition, a preservation in the colonic absorptive function was also observed, and this effect can also account for the colonic protective effect observed in this model of acute colitis.
Abbreviations
IBD:Inflammatory bowel disease
LTB4:Leukotriene B4
MDA:Malonyldialdehyde
MPO:Myeloperoxidase
TNBS:Trinitrobenzenesulfonic acid
References
-
1
Campos R, Garrido A, Guerra R, Valenzuela A.
Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver.
Planta Medica.
1989;
55
417-9
-
2
Valenzuela A, Lagos C, Schmidt K, Videla L A.
Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat.
Biochemical Pharmacology.
1985;
34
2209-12
-
3
De la Puerta R, Martinez E, Bravo L, Ahumada M C.
Effect of silymarin on different acute inflammation models and on leukocyte migration.
Journal of Pharmacy and Pharmacology.
1996;
48
968-70
-
4
Alarcon de la Lastra C, Martin M J, Marhuenda E J.
Gastric anti-ulcer activity of silymarin, a lipoxygenase inhibitor, in rats.
Journal of Pharmacy and Pharmacology.
1992;
44
929-31
-
5
Harris M L, Schiller H J, Reilly P M, Donowitz M, Grisham M B, Bulkley G B.
Free radicals and other reactive oxygen metabolites in inflammatory bowel disease: Cause, consequence or epiphenomenon?.
Pharmacology and Therapeutics.
1992;
53
375-408
-
6 Stenson W F. Inflammatory bowel disease: from bench to bedside, 13. Animal models of inflammatory bowel disease. In: Targan SR, Shanahan F, editors Baltimore; Williams & Wilkins 1994: 180-92
-
7
Crespo M E, Galvez J, Cruz T, Ocete M A, Zarzuelo A.
Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS.
Planta Medica.
1999;
65
651-3
-
8
Veljaca M, Lesch C A, Pllana R, Sanchez B, Chan K, Guglietta A J.
BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats.
Journal of Pharmacology and Experimental Therapeutics.
1995;
272
417-22
-
9
Yamada T, Marshall S, Specian R D, Grisham M B.
A comparative study of two models of experimental colitis in rats.
Gastroenterology.
1992;
102
1524-34
-
10
Dehmlow C, Murawski N, de Groot H.
Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells.
Life Sciences.
1996;
58
1591-600
-
11
Sharon P, Stenson W F.
Metabolism of arachidonic acid in acetic acid colitis in the rat: Similarity to human inflammatory bowel disease.
Gastroenterology.
1984;
86
453-60
-
12
Sanchez de Medina F, Galvez J, Romero J A, Zarzuelo A.
Effect of quercitrin on acute and chronic experimental colitis in the rat.
The Journal of Pharmacology and Experimental Therapeutics.
1996;
278
771-9
-
13
Valenzuela A, Aspillaga M, Vial S, Guerra R.
Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat.
Planta Medica.
1989;
55
420-2
-
14 Sciuto A M. Antioxidant properties of glutathione and its role in tissue protection. In: Baskin SI, Salem H, editors Oxidants, antioxidants and free radicals. Washington; Taylor & Francis 1997: 171-91
-
15
McHugh K J, Svensjö E, Persson C GA.
Exudative and absorptive permeability in different phases of an experimental colitis condition.
Scandinavian Journal of Gastroenterology.
1996;
31
900-5
-
16
Bell C J, Gall D G, Wallace J L.
Disruption of colonic electrolyte transport in experimental colitis.
American Journal of Physiology.
1995;
268
G622-30
-
17
Cruz T, Galvez J, Ocete M A, Crespo M E, Sanchez de Medina F, Zarzuelo A.
Oral administration of rutoside can ameliorate inflammatory bowel disease in rats.
Life Sciences.
1998;
62
687-95
-
18
Ocete M A, Galvez J, Crespo M E, Cruz T, Gonzalez M, Torres M I et al.
Effects of morin on an experimental model of acute colitis in rats.
Pharmacology.
1998;
57
261-70
-
19
Manna S K, Mukhopadhyay A, Van N T, Aggarwal B B.
Silymarin suppresses TNF-induced activation of NF-kappaB, c-jun N-terminal kinase, and apoptosis.
The Journal of Immunology.
1999;
163
6800-9
-
20
Stack W A, Mann S D, Roy A J, Heath P, Sopwith M, Freeman J et al.
Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease.
Lancet.
1997;
349
521-4
Prof. Dr. Julio Galvez
Department of Pharmacology,
School of Pharmacy, University of Granada
Campus Universitario “La Cartuja” s/n
E-18071 Granada
Spain
Email: jgalvez@platon.ugr.es
Fax: +34958248964
