HEPATIC OXIDANT INJURY AND GLUTATHIONE DEPLETION DURING TOTAL PARENTERAL-NUTRITION IN WEANLING RATS

Hepatobiliary dysfunction occurs commonly in infants on prolonged pare nteral nutrition alimentation; however, the underlying mechanisms caus ing liver injury are poorly understood. We postulated that oxidant str ess played a significant role in parenteral nutrition-induced liver ab normalities and tested this hypothesis in a rat model. Weanling male r ats received 8 days of total parenteral nutrition (TPN) through a cent ral venous catheter (TPN group), pair feeding of rat chow and placemen t of a central venous catheter (sham group), or ad libitum feedings of rat chow (control group). After 8 days of TPN, serum alanine aminotra nsferase and cholylglycine levels were elevated, hepatocellular steato sis was present, hepatic mitochondria had dilated intracristal spaces, and lipid peroxidation of mitochondria was increased compared with sh am 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 da ys of TPN. Sham and control rats showed no evidence of mitochondrial l ipid peroxidation or liver injury after 8 days. Removal of metabisulfa te from TPN solutions and addition of cysteine HCl or choline had no m ajor effect on these findings. Bacterial translocation was not increas ed in TPN rats. These data suggest that glutathione depletion and oxid ant stress are important factors in the pathogenesis of TPN-induced li ver abnormalities in the weanling rat.