Tert‐butylhydroquinone promotes skin flap survival by inhibiting oxidative stress mediated by the Nrf2/HO‐1 signalling pathway

Author:

Wang Kaitao1,Wang An1,Deng Jiapeng1,Yang Jialong1,Chen Guodong1,Chen Qingyu1,Ye Minle1,Lin Dingsheng1

Affiliation:

1. Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine Wenzhou Medical University Wenzhou China

Abstract

Background and PurposeSkin flaps are among the most important means of wound repair in clinical settings. However, partial or even total distal necrosis may occur after a flap operation, with severe consequences for both patients and doctors. This study investigated whether tert‐butylhydroquinone (TBHQ), a known agonist of the transcription factor nuclear factor erythroid 2‐related factor 2 (Nrf2), and an antioxidant, could promote skin flap survival.Experimental ApproachMcFarlane skin flap models were established in male Sprague–Dawley rats and then randomly divided into control, low‐dose TBHQ, and high‐dose TBHQ treatment groups. On postoperative day 7, the survival and blood flow of the skin flaps were assessed. Using flap tissue samples, angiogenesis, inflammation, apoptosis, autophagy, and Nrf2/haem oxygenase 1 (HO‐1) signalling pathway activity were measured with immunohistochemical techniques and western blotting.Key ResultsTBHQ dose‐dependently stimulated the Nrf2/HO‐1 signalling pathway, inducing autophagy through the up‐regulation of LC3B and beclin 1 and concurrently suppressing p62 expression. Additionally, TBHQ hindered apoptosis by enhancing Bcl‐2 expression while inhibiting the expression of Bax. It suppressed inflammation by inhibiting the expression of interleukin 1β, interleukin 6, and tumour necrosis factor‐α and enhanced angiogenesis by promoting the expression of vascular endothelial growth factor.Conclusion and ImplicationsIn summary, TBHQ promoted flap survival in rats by up‐regulating the Nrf2/HO‐1 signalling pathway. As TBHQ is already widely used as a food additive, it could offer an acceptable means of improving clinical outcomes following skin flap surgery in patients.

Publisher

Wiley

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