Effects of Silymarin on the Proliferation and Glutathione Levels of Peripheral Blood Mononuclear Cells From Β-Thalassemia Major Patients Publisher Pubmed



Alidoost F¹ ; Gharagozloo M¹ ; Bagherpour B¹ ; Jafarian A² ; Sajjadi SE³ ; Hourfar H⁴ ; Moayedi B¹ Show Affiliations
Source: International Immunopharmacology Published:2006

Abstract

Iron toxicity in β-thalassemia major is the main cause of oxidative stress and cell mediated immune deficiencies. Despite indicative signs of severe oxidative deficiencies associated with β-thalassemia major, such as decreased level of plasma antioxidants and depletion of erythrocyte glutathione, little is known about intracellular redox status of immune cells. Since glutathione is a primary intracellular antioxidant and plays an essential role in several functions in T cells, in this study intracellular glutathione (GSH) levels as well as proliferation of PHA-activated peripheral blood mononuclear cells (PBMC) were investigated in 28 β-thalassemia major patients and 28 healthy age-matched individuals. Considering the potential benefits of flavonoids in the therapy of oxidative stress, the effects of silymarin on the GSH levels and proliferation of PBMC from normal and thalassemia individuals were further examined. Quantitative determination of intracellular GSH and proliferative response of PBMC to PHA were performed before and after 72 h incubation of PBMC with various concentrations of silymarin (0, 5, 10, or 20 μg/ml). Results demonstrated a significant reduction of GSH and proliferation in β-thalassemia major cells; however treatment with silymarin led to restoration of both GSH levels and PBMC proliferation in thalassemia patients. Considerably low levels of GSH and depressed proliferative response of PBMC in β-thalassemia major may be responsible for the cell mediated immune abnormalities in iron overload conditions. Moreover, the GSH restoration and improvement of PBMC growth by silymarin is a possible explanation for its recently reported antioxidant and immunostimulatory activities. These data suggest the benefit of using flavonoids to normalize immune dysfunction in β-thalassemia major. The immunomodulatory effects of silymarin in β-thalassemia major are currently under further investigation in a double blind clinical trial. © 2006 Elsevier B.V. All rights reserved.