Paracetamol can exacerbate irradiation-induced DNA damage.

Abstract

Paracetamol is one of the most commonly used drugs for short-term pain relief. If taken in excess, the toxic metabolite (N-acetyl-p-benzoquinone imine) is formed. This can be inactivated through conjugation with the antioxidant glutathione but results in glutathione depletion and subsequent oxidative damage to hepatocytes [1]. Although the main route of paracetamol bioactivation is via the P450 cytochrome system in the liver, these enzymes are also present in most other tissues of the body. In tissues where this activity is low (such as the skin and lung), prostaglandin synthetase can catalyse the production of the toxic metabolite [2]. Recent work in vitro has shown that glutathione depletion is possible in lung cells incubated with therapeutic concentrations of paracetamol [3]. As glutathione plays an important role in the antioxidant defence of the skin to UVA irradiation [4], anything that depletes cellular glutathione levels could potentially exacerbate the cellular damage caused by such an insult and consequently have detrimental health effects.