Bilirubin: a promising antioxidant for ischaemia/reperfusion injury

Dear Editors, We read with great interest the article by Ahanger et al. entitled ‘Pro-healing effects of bilirubin in open excision wound model in rats’ (1). In this study, the authors hypothesised that bilirubin, which is known as a strong antioxidant, could be of potential therapeutic value in wound healing in open excision wound models in rats. To validate their hypothesis, they made a full-thickness wound in rats. Their results revealed that percentage contraction of wounds in bilirubin-treated rats was significantly greater (P< 0⋅01 on day 4 and P< 0⋅001 on days 7 and 10) as compared with that in vehicle-treated rats, on respective days. Their control group (group I) rats were administered with normal saline intraperitoneally once every day for 9 days, while the experimental group (group II) was administered with bilirubin (solubilised in 0⋅1 M NaOH and pH was adjusted to 8⋅0 with 0⋅1 M HCl) intraperiotoneally once every day for 9 days. First, the authors did not check serum bilirubin level in rats and they concluded that this could be a new agent for enhancing cutaneous wound healing ‘I think checking serum bilirubin level would be valuable to evaluate the effect of bilirubin on cutaneous wound healing’. Second, as this experiment was conducted on rats with or without hyperbilirubinemia, the title ‘The effect of hyperbilirubinemia on the wound contraction in a rat model’ would better explain their results. Third, wound contraction in rats is not reliable in terms of their low skin tension. To validate their hypothesis, future studies using a pig model would be much helpful. Recently, patients with Gilberts’ syndrome (which is characterised by mild elevated serum bilirubin) were found to live longer than the average population during long-term follow-up, and this is mainly due to the less incidence of ischaemic heart disease. Kang et al. also reported that elevated serum bilirubin levels are inversely associated with coronary artery atherosclerosis (2). From bed to bench, one recent experimental study showed that intraperitoneal bilirubin administration decreases the infarct area in a rat coronary ischaemia/reperfusion injury model (3). Bilirubin might be of great value to the reconstructive surgeon and patients in the near future and require further continuing research in terms of ischaemia/reperfusion injury.