Abstract

Anastomotic leakage is a devastating complication of colorectal surgery. Neoadjuvant radiotherapy for colorectal cancer can affect the mechanical and biochemical parameters of anastomotic healing. It has been reported that ozone increases antioxidant enzyme activity and stimulates adaptive processes to oppose the pathophysiologic conditions mediated by reactive oxygen species (ROS). The objective of this study was to investigate the effect of controlled administration of ozone on the healing of anastomosis and the activation of antioxidant enzymes in the colon after radiotherapy. Rats (n = 48) were randomly assigned to the following groups: control groups (1 and 2), saline-treated and irradiated (IR) groups (3 and 4) and ozone oxidative preconditioning (OOP) and IR groups (5 and 6). Rats were exposed to whole-body IR (6 Gy) after pretreatment with either saline or ozone. Rats in groups 1, 3 and 5 were euthanized on postoperative day 3, whereas those in groups 2, 4 and 6 were euthanized on postoperative day 7. The anastomoses were performed on day 7 post-IR. The anastomotic segment was resected to measure hydroxyproline (HPO) content, myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration and for histopathological evaluation. The mean bursting pressure of the groups that underwent radiotherapy was lower than that of the control groups (p < 0.001). In groups 5 and 6, the tissue HPO concentrations were higher than those in groups 3 and 4. Although mean values for MPO activity in groups 5 and 6 were higher than those in groups 3 and 4, the differences were not significant. Regarding oxidative damage markers, MDA concentrations were significantly lower in group 5 than those in group 3. In this experimental model, OOP exerted favorable effects on colon anastomotic healing after radiation exposure.

Highlights

  • Anastomotic leakage after colorectal surgery is a dreaded complication, as it greatly increases morbidity and mortality and has been associated with high local recurrence and diminished survival after colorectal cancer surgery.[1]

  • It has been reported that ozone increases antioxidant enzyme activity and stimulates adaptive processes to oppose the pathophysiologic conditions mediated by reactive oxygen species (ROS)

  • Preoperative radiotherapy is being successfully used as an adjuvant in rectal cancer therapy, but the ionized beams used in radiotherapy can potentially damage organs by increasing the cellular oxidative stress as a result of molecular ionization, leading to the overproduction of reactive oxygen species (ROS).[2,3]

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Summary

Introduction

Anastomotic leakage after colorectal surgery is a dreaded complication, as it greatly increases morbidity and mortality and has been associated with high local recurrence and diminished survival after colorectal cancer surgery.[1] Preoperative radiotherapy is being successfully used as an adjuvant in rectal cancer therapy, but the ionized beams used in radiotherapy can potentially damage organs by increasing the cellular oxidative stress as a result of molecular ionization, leading to the overproduction of reactive oxygen species (ROS).[2,3] Ozone (O3) therapy is widely used in medicine for its antioxidant, anti-inflammatory and antimicrobial effects.[4] The therapeutic effect of O3 targets reactive oxygen products, hydrogen peroxide and lipid oxidation products (LOPs).[5] it has been hypothesized that O3 is effective in preventing ischemia–reperfusion damage and has been used as a therapeutic option in ischemia–reperfusion studies.[6,7] The term ‘O3 oxidative preconditioning’ (OOP) implies the triggering of an adaptation to oxidative stress through the application of O3 at repeated non-toxic doses. It has been reported that ozone increases antioxidant enzyme activity and stimulates adaptive processes to oppose the pathophysiologic conditions mediated by reactive oxygen species (ROS)

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