Hepatic oxidant injury and glutathione depletion during total parenteral nutrition in weanling rats.

Hepatobiliary dysfunction occurs commonly in infants on prolonged parenteral nutrition alimentation; however, the underlying mechanisms causing liver injury are poorly understood. We postulated that oxidant stress played a significant role in parenteral nutrition-induced liver abnormalities and tested this hypothesis in a rat model. Weanling male rats received 8 days of total parenteral nutrition (TPN) through a central venous catheter (TPN group), pair feeding of rat chow and placement of a central venous catheter (sham group), or ad libitum feedings of rat chow (control group). After 8 days of TPN, serum alanine aminotransferase and cholylglycine levels were elevated, hepatocellular steatosis was present, hepatic mitochondria had dilated intracristal spaces, and lipid peroxidation of mitochondria was increased compared with sham and control groups. Hepatic glutathione levels decreased to 16% of control values after 5 days of TPN; this was followed by mitochondrial lipid peroxidation and elevated serum cholylglycine levels after 8 days of TPN. Sham and control rats showed no evidence of mitochondrial lipid peroxidation or liver injury after 8 days. Removal of metabisulfate from TPN solutions and addition of cysteine HCl or choline had no major effect on these findings. Bacterial translocation was not increased in TPN rats. These data suggest that glutathione depletion and oxidant stress are important factors in the pathogenesis of TPN-induced liver abnormalities in the weanling rats.

Effect of vitamin E on transport processes in isolated rat hepatocytes.

Vitamin E deficiency is a common consequence of chronic cholestatic liver disorders. Inasmuch as vitamin E content of cellular membranes alters membrane properties such as fluidity and molecular order, we postulated that vitamin E status could affect hepatocyte transport processes dependent on membrane integrity. Hepatocytes were isolated from rats maintained on diets containing deficient, sufficient, or excess vitamin E. Cell viability and oxygen consumption were maintained in all groups of hepatocytes. Hepatocyte uptake of taurocholic acid and ouabain and Na+,K(+)-ATPase activity estimated by rubidium-86 influx did not differ with vitamin E status. Vitamin-E-deficient hepatocytes had increased generation of lipid peroxide products. We conclude that deficient or excess vitamin E status had little effect on selected transport processes in normal hepatocytes.