INTRODUCTION: Smoking poses a risk to flap viability, with nicotine being a major contributor to the formation of free radicals. Allopurinol, known for its antioxidant properties, has been shown to enhance tissue survival in ischemic conditions by reducing the production of reactive oxygen species (ROS). This study aims to assess the impact of allopurinol on the viability and success of skin flaps in Wistar rats exposed to nicotine. METHODS: This study examined skin flap survival in nicotine-exposed rats treated with allopurinol. Twenty-eight rats were separated into two groups. During 1 month of nicotine exposure, the treatment group received systemic allopurinol 7 days before and 2 days after the flap procedure, while the control group received no allopurinol. Pro-angiogenic factors, proinflammatory factors, anti-inflammatory factors, and oxidative markers were assessed on the 7th day after the flap procedure using enzyme-linked immunosorbent assay method. Macroscopic flap viability was evaluated on the 7th day using Image J photos. RESULTS: As an oxidative marker, malondialdehyde levels were significantly lower in rats given allopurinol than in controls (P < 0.001). The levels of interleukin 6 and tumor necrosis factor α, as markers of inflammatory factors, were significantly lower in the group of rats given allopurinol compared to controls (P < 0.001). The level of angiogenesis in rats given allopurinol, measured by vascular endothelial growth factor levels, was also higher in the treatment group compared to controls (P < 0.001). Macroscopically, the percentage of distal flap necrosis in Wistar rats given allopurinol was lower and statistically significant compared to controls (P < 0.001). CONCLUSIONS: Xanthine oxidoreductase is part of a group of enzymes involved in reactions that produce ROS. Allopurinol, as an effective inhibitor of the xanthine oxidase enzyme, can reduce oxidative stress by decreasing the formation of ROS. This reduction in oxidative stress mitigates the risk of ischemic-reperfusion injury effects and significantly increases the viability of Wistar rat flaps exposed to nicotine.

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