Role of TNF-α and the NF-κB pathway in drug-induced organ injuries

Benedetti, G.O.E. (2013)

Doctoral Thesis

Drug-induced organ toxicity is a major concern for pharmaceutical industry, due to removal of a high number of drugs from the market, as well as for public health, due to numerous hospitalizations and patient death. The organs that are the primary target for such toxicities are the liver and the kidneys since both organs are continuously exposed to high concentrations of drugs and have high metabolic capacities. The immune system has been shown to be involved in the toxicity of several drugs- inducing liver and kidney injury. In particular, the cytokine tumor necrosis factor _ (TNF-_) has been shown to be the main constituent of the inflammatory processes responsible for the aggravation of drug-induced liver and kidney injuries. In this thesis, the role of TNF-_ in drug-induced organ injury was investigated. The main question was to assess the possible synergy between TNF-_ and druginduced cytotoxicities, and to unravel the underlying molecular mechanisms of such a synergy.

• toxicogenomics
• TNF-_
• RNA interference
• Pathway
• Organ toxicity
• NF-_B
• NF-kappaB
• Liver
• Kidney
• In vitro
• Drug-induced toxicity
• Drug

• All authors: Benedetti, G.O.E.
• Supervisor: Water, B. van de
• Co-supervisor: Graauw, M. de
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Science, Leiden University
• Date: 2013-05-07
• ISBN (print): 9789461822567