Influence of dietary methyl group donors on survival time after hemorrhage in an inbred rat strain

Abstract

Our initial experiments with survival time after hemorrhage (STaH) in inbred rats revealed large intra‐strain differences in STaH, associated blood measures, and global DNA methylation levels. We hypothesized that feeding inbred rats post‐weaning diets varying in methyl group donors (MGDs; folic acid, choline, methionine and vitamin B12) starting at 4 weeks age for 9 weeks, may influence STaH and intra‐strain variability via altered DNA methylation patterns. To address this hypothesis, BN/Mcwi rats were randomly assigned to one of 4 diet groups: natural control (NC, n=13), synthetic control (SC, n=11), synthetic deficient (SD, n=6; 50–100% less MGDs than NC/SC) and synthetic supplemented (SS, n=11; 3–10 fold more MGDs than NC/SC). Each rat was bled to 50% of its blood volume and STaH observed up to 240 min. STaH was lower (p<0.01) in deficient rats (SD) compared to other diet groups: NC (110 ± 22 min), SC (141 ± 28 min), SD (27 ± 4 min), SS (166 ± 23 min). There were no differences in STaH between NC vs SC (p=0.84), SC vs SS (p=0.37), or NC vs SS (p=0.07). Percentages of survivors (ST=240 min) were: NC=23%, SC=36%, SD=0%, SS=45% (p=0.22). Coefficients of variation for STaH were not different among diets (p>0.25; NC=72.6%; SC=66.5%; SD=35.8%; SS=44.9%). Hence, SD diet decreased survival after hemorrhage, but dietary effects on DNA methylation patterns and other phenotypes are yet to be determined. (Funding by USAMRMC).