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The effects of tacrolimus on colonic anastomotic healing in rats

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Aim

The aim of this experimental study is to investigate the effects of tacrolimus on colonic anastomotic healing after subcutaneous administration.

Materials and methods

Forty Albino–Wistar male rats were divided into two groups, with two equal subgroups each. They all underwent colonic resection followed by a single-layer, inverted colon anastomosis and were injected subcutaneously with either 1 ml of 0.9% NaCl solution or tacrolimus (0.1 mg/kg body weight) depending on their group. Half of the rats were sacrificed on the fourth postoperative day, while the remaining half were sacrificed on the eighth postoperative day. Macroscopical and histological assessment was performed, while anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were evaluated.

Results

On the fourth postoperative day, the bursting pressures (217.00 ± 11.12, p < 0.001), the fibroblast activity (2.80 ± 0.42, p = 0.022), the neoangiogenesis (2.10 ± 0.32, p = 0.007) and the tissue hydroxyproline concentration (254.23 ± 67.10, p = 0.001) were significantly higher in the tacrolimus-treated animals. Furthermore, tacrolimus significantly decreased the inflammatory cell infiltration (1.50 ± 0.53, p < 0.001) and the tissue collagenase I concentration (4.16 ± 0.76, p = 0.002).

On the eighth day, the bursting pressure (264.00 ± 32.61, p < 0.001) and the hydroxyproline tissue concentration (331.04 ± 55.56, p = 0.002) were significantly higher in the tacrolimus subgroups. The inflammatory cell infiltration (1.20 ± 0.42, p < 0.001) and the collagenase I concentration (1.61 ± 0.83, p < 0.001) were significantly lower. In addition, the adhesion formation score was significantly lower (1.20 ± 0.92, p = 0.065).

Conclusion

Tacrolimus, when injected subcutaneously, promotes healing of colonic anastomoses in rats. It impairs not only inflammatory response but also collagen degradation, resulting to increased anastomotic strength on the fourth as well as on the eighth postoperative day.

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Acknowledgements

The authors wish to acknowledge the contribution of Dr. G. Menexes, lecturer of Biometry in Aristotle University of Thessaloniki, to the statistical analysis of this study. Mrs. Vasiliki Kanellou, BA in English Language and Linguistics, MA in Applied Linguistics, is also acknowledged for proof reading and revising the paper.

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Authors and Affiliations

  1. 4th Surgical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

    D. Raptis, I. Mantzoros, M. G. Pramateftakis, K. Despoudi, I. Kanellos & Ch. Lazarides

  2. Histopathology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

    T. Zaraboukas

  3. Biochemical Laboratories, Aristotle University of Thessaloniki, Thessaloniki, Greece

    G. Koliakos

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  1. D. Raptis
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  2. I. Mantzoros
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  3. M. G. Pramateftakis
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  4. K. Despoudi
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  5. T. Zaraboukas
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  6. G. Koliakos
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  8. Ch. Lazarides
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Correspondence to D. Raptis.

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Raptis, D., Mantzoros, I., Pramateftakis, M.G. et al. The effects of tacrolimus on colonic anastomotic healing in rats. Int J Colorectal Dis 27, 299–308 (2012). https://doi.org/10.1007/s00384-011-1337-y

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