Effects of Diet on Late Radiation Injuries in Rats

Abstract

It has been speculated that the addition of antioxidants to diet could act as either radioprotectors or as mitigators of radiation injury. In preparation for studies of the mitigation efficacy of antioxidants, rats were placed on a modified version of AIN-76A, the diet typically used in such studies. This AIN-76A diet is refined and has no synthetic antioxidants or isoflavones. Compared to the natural-ingredient Teklad 8904 diet used in previous studies, use of the AIN-76A diet from 1-18 weeks after irradiation significantly reduced injury in a radiation nephropathy model. A confirmation study included an additional arm in which the AIN-76A diet was started 2 weeks prior to irradiation; again, the switch to AIN-76A post-irradiation mitigated radiation nephropathy (p<0.001), but switching to the AIN-76A diet pre-irradiation had no effect (p>0.2). The two diets do not differ in salt content, but the AIN-76A diet is somewhat lower in protein (18% vs. 24%). The protein source (primarily soy in Teklad 8904 versus casein in AIN-76A) might explain the effects. However, replacing the casein in AIN-76A with soy did not change the mitigation efficacy of the diet (p>0.2 for comparison of the different AIN-76A diets). A similar study in a rat radiation pneumonitis model also suggested mitigation by post-irradiation use of AIN-76A, although the effect was not statistically significant (p=0.07). In conclusion, base diet alone can have biologically-significant effects on organ radiosensitivity, but the mechanistic basis for the effect and its dependence of timing relative to irradiation are unclear.

Rat Models of Partial-body Irradiation with Bone Marrow-sparing (Leg-out PBI) Designed for FDA Approval of Countermeasures for Mitigation of Acute and Delayed Injuries by Radiation

“…Two weeks prior to irradiation, rats were switched to a moderate antioxidant diet (Teklad 2018 Global 18% protein rodent diet, Envigo, Madison, WI); diet details are listed in Table 1. The Teklad 2018 global diet has been used at other institutions for rodent radiation studies (Patterson et al 2021; Booth et al 2012a and b, 2015) and is a better reflection of the human diet than Teklad 8604/8904 used previously (Fish et al 2016, 2020; Moulder et al 2019).…”

“…It is well known that antioxidants can alter the radiation sensitivity in animals (Brown et al 2010;Kennedy et al 2011;Johnke et al 2014;Singh et al 2017). WAG/RijCmcr rats on diets depleted of isoflavones demonstrated increased sensitivity to radiation (Moulder et al 2019). Therefore, a moderate antioxidant diet, Teklad 2018, that contained an isoflavone content of 150-250 mg kg −1 was selected to replace Teklad 8604 (containing 350-550 mg isoflavones kg −1 ) used in previous studies (Fish et al 2016(Fish et al , 2020.…”

“…The goal herein was to optimize and fully assess adult female and male rat models of leg-out PBI that manifested lethal GI, lung, and kidney damage, while also assessing hematopoietic injury after irradiation. The goal required the radiation dose, diet, and supportive care to be refined based on previous studies (Fish et al 2016(Fish et al , 2020Moulder et al 2019) and as described in the results herein.…”

Mitigation of Multi-Organ Radiation Injury with ACE2 Agonist Diminazene Aceturate

“…WAG/RijCmcr rats were bred and maintained in a barrier facility at our institution. Two weeks prior to irradiation, rats were switched to a moderate antioxidant diet (Teklad Global 2018 diet) which is more representative of antioxidant levels in a human diet (18). All rats were provided reverse osmosis hyper-chlorinated water ad libitum.…”