Combined therapy of silymarin and desferrioxamine in patients with β-thalassemia major: a randomized double-blind clinical trial

• Published in: Fundamental & clinical pharmacology Vol. 23; no. 3; pp. 359 - 365
• Main Authors: Gharagozloo, Marjan, Moayedi, Behjat, Zakerinia, Maryam, Hamidi, Mehrdad, Karimi, Mehran, Maracy, Mohammad, Amirghofran, Zahra
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2009; Blackwell
• Subjects: Adolescent; Adult; Alkaline Phosphatase - drug effects; Alkaline Phosphatase - metabolism; Anemias. Hemoglobinopathies; Antioxidants - administration & dosage; Antioxidants - adverse effects; Antioxidants - therapeutic use; beta-Thalassemia - drug therapy; beta-Thalassemia - physiopathology; Biological and medical sciences; Deferoxamine - administration & dosage; Deferoxamine - adverse effects; Deferoxamine - therapeutic use; desferrioxamine; Diseases of red blood cells; Double-Blind Method; Drug Therapy, Combination; Erythrocytes - drug effects; Erythrocytes - metabolism; Female; Ferritins - blood; Ferritins - drug effects; Follow-Up Studies; Glutathione - blood; Glutathione - drug effects; Hematologic and hematopoietic diseases; Humans; iron overload; Liver - drug effects; Liver - enzymology; Male; Medical sciences; Metabolic diseases; Metals (hemochromatosis...); Other metabolic disorders; Pharmacology. Drug treatments; Siderophores - administration & dosage; Siderophores - adverse effects; Siderophores - therapeutic use; silymarin; Silymarin - administration & dosage; Silymarin - adverse effects; Silymarin - therapeutic use; Young Adult; β-thalassemia major; Human; Iron overload; Hemoglobinopathy; silymarin; Metabolic diseases; Hemopathy; Iron; Flavonoid; Genetic disease; Deferoxamine; Polyphenol; Randomization; Hemolytic anemia; desferrioxamine; β-Thalassemia; Silibinin; Chelating agent; Phenols; Double blind study; Clinical trial; Combined treatment; Antidote; β-thalassemia major
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/j.1472-8206.2009.00681.x

Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, and iron chelating activities. The present study was designed to investigate the therapeutic activity of orally administered silymarin in patients with thalassemia major under conventional iron chelation therapy. A 3‐month randomized, double‐blind, clinical trial was conducted in 59 β‐thalassemia major patients in two well‐matched groups. Patients were randomized to receive a silymarin tablet (140 mg) three times a day plus conventional desferrioxamine therapy. The second group received the same therapy but a placebo tablet instead of silymarin. Clinical laboratory tests were assessed at the beginning and the end of the trial, except for serum ferritin level that was assessed at the middle of the trial as well. Results of this study revealed that the combined therapy was well tolerated and more effective than desferrioxamine in reducing serum ferritin level. Significant improvement in liver alkaline phosphatase and glutathione levels of red blood cells was also observed in silymarin‐treated β‐thalassemia patients. However, no significant difference in serum ferritin levels was detected between silymarin and placebo groups after 1.5 and 3 months treatment, probably because of insufficient sample size to detect subtle changes in ferritin levels between groups. This is the first report showing the beneficial effects of silymarin in thalassemia patients and suggests that silymarin in combination with desferrioxamine can be safely and effectively used in the treatment of iron‐loaded patients.