N-3 fatty acids ameliorate radiation-induced liver injury in the rat

Abstract

Irradiation causes veno-occlusive liver disease and radiation hepatitis. N-3 fatty acids are rapidly incorporated in the cellular membranes and modulate anti-inflammatory cytokines production, thus pretreatment with them could be an effective prevention modality to the effects of ionizing radiation. The purpose of this study was to investigate the effect of n-3 fatty acids on liver hemodynamics and microscopic appearance after ionizing radiation treatment. Three groups of rats were exposed to a single dose of 11 Gy of gamma radiation or sham radiation. Group control [C] was treated for 7d before radiation with standard rat chow, group fasted [F] with rat chow but fasted for the last 12 hours, and group n-3 with rat chow plus n-3 fatty acids. At days (d) 1, 3, 7, 15 and 30 post-radiation 2 rats per study-group were subjected to liver microcirculation assessment by means of laser-Doppler flowmetry and the livers were then processed for histology and immunohistochemistry. Liver microcirculation was decreased progressively from d1 to d30 in groups F and C in relation to n-3. Histological examination revealed dilatation of central veins and congestion of portal sinusoids on d1, hepatocyte degeneration on d3 and progressive hepatocyte necrosis from d7 up to d30. These findings were less prominent in group n-3 in relation to F and C. Apoptosis induction, assessed by means of Bax, was found to be less prominent in F and C groups in relation to n-3, while, when assessed by means of Bacl-2 and Bcl-xL, it was found to be expressed in F and C rather than in n-3 group, throughout the whole study period. It is concluded that n-3 fatty acids protect the rat liver from radiation-induced injury and thus patients eligible for abdominal radiotherapy could theoretically get the benefit of liver protection, by receiving an oral supplementary nutrition containing n-3 fatty acids for at least seven days prior to treatment. However, further investigation is needed.