MUSCLE PHYSIOLOGY Oxidative stress and DNA damage signalling in skeletal muscle in pressure-induced deep tissue injury Thomas K. Sin & Xiao M. Pei & Bee T. Teng & Eric W. Tam & Benjamin Y. Yung & Parco M. Siu Received: 11 July 2012 / Revised: 16 November 2012 / Accepted: 9 December 2012 / Published online: 16 January 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract The molecular mechanisms that contribute to the pathogenesis of pressure-induced deep tissue injury are largely unknown. This study tested the hypothesis that ox- idative stress and DNA damage signalling mechanism in skeletal muscle are involved in deep tissue injury. Adult Sprague Dawley rats were subject to an experimental pro- tocol to induce deep tissue injury. Two compression cycles with a static pressure of 100 mmHg was applied to an area of 1.5 cm 2 over the mid-tibialis region of right limb of the rats. The left uncompressed limb served as intra-animal control. Muscle tissues underneath compression region were collected for examination. Our analyses indicated that path- ohistological characteristics including rounding contour of myofibres and extensive nuclei accumulation were appar- ently shown in compressed muscles. The elevation of 8OHdG immunopositively stained nuclei indicated the pres- ence of oxidative DNA damage. Increase in oxidative stress was revealed by showing significant elevation of 4HNE and decreases in mRNA abundance of SOD1, catalase and GPx, and protein content of SOD2 in compressed muscles relative to control muscles. Increase in nitrosative stress was dem- onstrated by significant elevation of nitrotyrosine and NOS2 mRNA content. The activation of tumor suppressor p53 sig- nalling was indicated by the remarkable increases in protein contents of total p53 and serine-15 phosphorylated p53. The transcript expression of the DNA-repairing enzyme, Rad23A, was significantly suppressed in compressed muscles. Our time-course study indicated that increased oxidative/nitrosa- tive stress and proapoptotic signalling were maintained in muscles receiving increasing amount of compression cycles and post-compression time. Furthermore, resveratrol was found to attenuate the histological damage, oxidative/nitro- sative stress and proapoptotic signalling in response to pro- longed moderate compression. In conclusion, our findings are consistent with the hypothesis that oxidative stress and DNA damage signalling in skeletal muscle are involved in the underlying mechanisms responsible for the pathogenesis of pressure-induced deep tissue injury. Keywords Deep pressure ulcer . Resveratrol . Reactive oxygen species . Apoptosis Introduction Pressure ulcer, also known as pressure sore, bedsore or decubitus ulcer, is defined as the localized ulcerated tissues breakdown caused by sustained mechanical pressure in the body support interface. Pressure ulcer represents a consid- erable clinical problem as it frequently occurs in individuals with diminished mobility such as frail, infirm elderly and patients with spinal cord injury [2, 33, 46, 47]. The popula- tions particularly vulnerable to pressure ulcer include those of prolonged bedridden, wheelchair bound and orthoses/ prostheses clients. In addition to the impact on the daily living activities of the sufferers, pressure ulcer imposes a tremendous burden on social health care cost. It is estimated that over $1.3 billion is spent annually to manage the health problems in relation to pressure ulcer in the USA [16]. In UK, pressure ulcer has been estimated to cost £1.4–2.1 billion annually (4 % of total National Health Service ex- penditure), with most of the cost being attributed to the additional nursing care required [3]. The US National Pressure Ulcer Advisory Panel (NPUAP) has revised the pressure ulcer staging system and introduced the term pressure-induced deep tissue injury to particularly T. K. Sin : X. M. Pei : B. T. Teng : E. W. Tam : B. Y. Yung : P. M. Siu (*) Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China e-mail: parco.siu@polyu.edu.hk Pflugers Arch - Eur J Physiol (2013) 465:295–317 DOI 10.1007/s00424-012-1205-9