Silymarin as a preventive or therapeutic measure for chemotherapy and radiotherapy-induced adverse reactions: a comprehensive review of preclinical and clinical data

Abstract
Purpose Thus far, silymarin has been examined in several studies for prevention or treatment of various chemotherapy or radiotherapy-induced adverse reactions. In this review, we try to collect all available human, animal, and pre-clinical data in this field. Methods The search was done in Scopus, PubMed, Medline, and systematic reviews in the Cochrane database, using the following keywords: “Cancer,” “Chemotherapy,” “Radiotherapy,” “Mucositis,” “Nephrotoxicity,” “Dermatitis,” “Ototoxicity,” “Cardiotoxicity,” “Nephrotoxicity,” “Hepatotoxicity,” “Reproductive system,” “Silybum marianum,” “Milk thistle,” and “Silymarin” and “Silybin.” We included all relevant in vitro, in vivo, and human studies up to the date of publication. Results Based on 64 included studies in this review, silymarin is considered a safe and well-tolerated compound, with no known clinical drug interaction. Notably, multiple adverse reactions of chemotherapeutic agents are effectively managed by its antioxidant, anti-apoptotic, anti-inflammatory, and anti-immunomodulatory properties. Clinical trials suggest that oral silymarin may be a promising adjuvant with cancer treatments, particularly against hepatotoxicity (n = 10), nephrotoxicity (n = 3), diarrhea (n = 1), and mucositis (n = 3), whereas its topical formulation can be particularly effective against radiodermatitis (n = 2) and hand-foot syndrome (HFS) (n = 1). Conclusion Further studies are required to determine the optimal dose, duration, and the best formulation of silymarin to prevent and/or manage chemotherapy and radiotherapy-induced complications.