Oxidative stress as a mechanism underlying sulfasalazine-induced toxicity

Expert Opin Drug Saf. 2011 Mar;10(2):253-63. doi: 10.1517/14740338.2011.529898. Epub 2011 Jan 10.

Abstract

Introduction: Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease (CD) and rheumatoid arthritis (RA). A high incidence of side effects limits therapy with this drug. Getting a wider knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care, minimizing toxicity and inappropriate use.

Areas covered: This paper gives an overview of recent research about SASP and its main adverse effects, highlighting the mechanisms underlying them. To give an overview and comment on the data available so far on this topic, relevant literature was identified using a PubMed search of articles published up to December 2009. Search terms included: 'sulfasalazine', 'oxidative stress, 'renal effects', 'hepatotoxicity' and 'male fertility'. Original papers were reviewed and relevant citations from these articles were also considered.

Expert opinion: Although SASP and 5-aminosalicylic acid also scavenge ROS, which may account for some of their anti-inflammatory properties, the reaction with ROS may also generate toxic free radicals; hence, the ability of other antioxidants to suppress the toxicity of SASP in vivo. Further investigations, particularly about SASP mechanism, are still needed.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / physiopathology
  • Lipid Peroxidation / drug effects
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Sulfasalazine / adverse effects*
  • Sulfasalazine / pharmacology
  • Sulfasalazine / therapeutic use

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Reactive Oxygen Species
  • Sulfasalazine