A non-human primate model of radiation-induced cachexia.

Wanchang Cui,Allison M Gibbs,Cheryl Taylor-Howell,Pei Zhang,Kim G Hankey,Alexander W Bennett,Cassandra P Smith,Kory R Barrow,Sean R Kearney,Thomas J Macvittie

doi:10.1038/srep23612

Wanchang Cui, Allison M Gibbs + Show 8 more

Open Access

https://doi.org/10.1038/srep23612

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Journal: Scientific Reports	Publication Date: Mar 31, 2016
Citations: 22	License type: CC BY 4.0

Affiliation: University of Maryland, Baltimore

Abstract

Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20–25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease.

Highlights

Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy
The percentage was decreased in non-human primate (NHP) exposed to 12.0 and 12.5 Gy because these animals were euthanized before severe body weight (BW) loss could happen (Table 1)
The current study showed that high dose radiation exposure caused significant BW loss in a dose-threshold and time-dependent manner in a NHP model

Summary

Introduction

Muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease. The weight loss observed in patients receiving concurrent chemo-radiotherapy for non-small cell lung cancer occurred prior to the onset of esophagitis and without decreases in daily nutritional intake[10]. The ubiquitin-proteasome system (UPS) is the major proteolytic system that degrades proteins in all tissues including

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