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

Abstract

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.

Taurine and cholestasis associated to TPN. Experimental study in rabbit model

“…Theoretically, there are three mechanisms by which prolonged Ta deficit could be implicated in TPN-AC: instability caused by an alteration of hepatic membrane permeability [23,24], decreased antioxidant activity [25][26][27], and tauroconjugation deficiency [19,28,29]. The conjugation of BA seems to make them less toxic, especially Ta-conjugation, although there are differences Fig.…”

“…Hence, a Ta deficit could also affect BA excretion in this way. The oxidation hypothesis of Sokol and Moss [25][26][27] is logical considering the antioxidant properties of Ta and the epidemiological coincidence of low antioxidant levels and high-cholestasis incidence in the newborn, preterm, prolonged metabolic stress, and short bowel syndrome patients who underwent long-term TPN.…”

Glutamine attenuates TPN-associated liver injury in infant rabbits

“…Many studies have demonstrated that the capacity of antioxidants is impaired during total parenteral nutrition; for example, glutathione and β-carotene are decreased, while products of oxidative injury, such as MDA, are elevated, which might be imposed by lipid peroxidation or photooxidation of vitamins [9,15].…”

Photooxidation of Parenteral Multivitamins Induces Hepatic Steatosis in a Neonatal Guinea Pig Model of Intravenous Nutrition

“…TPN-related hepatic dysfunctions (25) have been linked to oxidant stress (26,27) as well as genetic (28,29), nutritional, environmental, and inflammatory factors (23). More specifically, the following nutritional factors have been associated with steatosis and/or cholestasis: enteral starvation (30,31), an amino acid imbalance (32,33), photo-oxidized products of amino acids (11,12,34), an excessive infusion of glucose (35) or lipids (36), a carbohydrate to nitrogen imbalance (37,38), and the source of infused lipids (39).…”