Oxidative stress is believed to accompany reperfusion and to mediate dysfunction of the liver after traumatic-
hemorrhagic shock (THS). Recently, endoplasmic reticulum (ER) stress has been suggested as an additional factor. This study investigated whether reperfusion after THS leads to increased oxidative and/or ER stress in the liver. In a rat model, including
laparotomy,
bleeding until decompensation, followed by inadequate or adequate reperfusion phase, three time points were investigated: 40 min, 3 h, and 18 h after
shock. The reactive
oxygen and
nitrogen species and its scavenging capacity (
superoxide dismutase 2), the
nitrotyrosine formation in
proteins, and the lipid peroxidation together with the status of
endogenous antioxidants (alpha-
tocopherylquinone-
alpha-tocopherol ratio) were investigated as markers for oxidative or nitrosylative stress. Mitochondrial function and
cytochrome P450 isoform 1A1 activity were analyzed as representatives for hepatocyte function. Activation of the
inositol-requiring
enzyme 1/X-box
binding protein pathway and up-regulation of the 78-kDa
glucose-regulated
protein were recorded as ER stress markers. Plasma levels of
alanine aminotransferase and Bax/Bcl-XL
messenger RNA (
mRNA) ratio were used as indicators for hepatocyte damage and apoptosis induction. Oxidative or nitrosylative stress markers or representatives of hepatocyte function were unchanged during and short after reperfusion (40 min, 3 h after
shock). In contrast, ER stress markers were elevated and paralleled those of hepatocyte damage. Incidence for sustained ER stress and subsequent apoptosis induction were found at 18 h after
shock. Thus, THS or reperfusion induces early and persistent ER stress of the liver, independent of oxidative or nitrosylative stress. Although ER stress was not associated with depressed hepatocyte function, it may act as an early trigger of protracted cell death, thereby contributing to delayed organ failure after THS.