Fractionated abdominal irradiation induces intestinal microvascular changes in an in vivo model of radiotherapy-induced gut toxicity

Abstract

Findings of this study provide evidence of regional and timing-specific changes in the intestinal microvasculature in response to fractionated radiotherapy which may play a role in development of both acute and chronic RIGT.

Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), angiostatin, and endostatin are increased in radiotherapy-induced gastrointestinal toxicity

“…Archival tissue from a prior study was utilised in the in vivo component of the present study, and experimental design has been previously described (Yeoh et al 2007;Stansborough et al 2017).…”

“…Sections of jejunum (30% of small intestinal length when measured from the pylorus) and colon (midlength of the large intestine) were collected as previously described and either formalin-fixed and paraffin-embedded, or snap frozen and stored at -80º (Yeoh et al 2007;Stansborough et al 2017).…”

“…RIGT is often divided into acute and chronic toxicity, with acute changes involving histopathological damage to villi and crypts, and chronic involving reactive fibrotic thickening (Yeoh et al 2007;Theis et al 2010). Previous research has suggested the involvement of the intestinal microvasculature in the development of RIGT, and several mediators have been investigated (Kruse et al 2004;Yeoh et al 2007;Stansborough et al 2017). NFκB, proinflammatory cytokines, and matrix metalloproteinases (MMPs) are all upregulated in the intestine following radiation, and have downstream effects on vascular mediators such as vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), von Willebrand factor (VWF), and the antiangiogenic mediators endostatin and angiostatin (Stansborough et al 2016).…”

“…Our previous studies have shown the intestinal microvasculature to be involved in RIGT, with apoptosis, cytostasis, telangiectasis, and fibrotic thickening occurring early and late following fractionated irradiation in dark agouti (DA) rats (Yeoh et al 2005;Stansborough et al 2017). In addition, several regulators of angiogenesis and vascular physiology including, but not limited to, TGFβ, VEGF, and VWF, are known to be altered in the intestine following irradiation (Wang et al 2001;Wang et al 2002;Milliat et al 2006;Lenting et al 2012;Boerma et al 2013).…”

The mechanism for the radioprotective effects of zymosan‐A in mice

“…Haematopoietic system is vulnerable to ionizing radiation (IR), and the failure of haematopoietic system is the major reason of death after acute radiation exposure . Radiation‐induced injury is a complex pathophysiological process . In general, DNA is the critical target of ionizing radiation.…”