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

Abstract

Taurine seems to be essential in the newborn for bile acid (BA) tauroconjugation, and its deficiency has been implicated in total parenteral nutrition-associated cholestasis (TPN-AC). Our purpose was to study the relationship between taurine (Ta) and TPN-AC in rabbits, which have a similar biliary metabolism to that of humans. We used 40 young rabbits, fed for 10 days according to the following four groups: GA [10] given TPN, with amino acid solution (AA) but without taurine (Ta) or its AA-precursors (methionine, cysteine, and serine); GB [10] the same but only without taurine; GC [10] the same but with taurine and its precursors; and GD [10] the control group with oral nutrition and saline infusion. Complete blood and bile analytical data were obtained and analyzed, including plasma AA and BA. Liver samples were studied under optical and electron microscopy. Serum: In GC there was a 20% increase in the AA-precursors, but paradoxically it was greater in GA. Bile: In GC there was 30% more excretion of total and free BA compared with less than 20% in GA and GB. Regarding toxic BA, there was a 15% decline in GLC3S excretion, but more than 20% in LCA excretion, than in GA and GB. Moreover, in GC the glyco-/tauro-conjugate ratio was worse than in the other groups. Histomorphology: While in GA and GB liver steatosis was diffuse (microsteatohepatitis type), in GC there was macrosteatosis with mitochondria-surrounded lipid droplets. In GA and GB, the canaliculi appeared dilated, with abundant bile plugs and loss of microvilli. There are signs that taurine may protect against TPN-AC. The mechanism does not seem to be BA tauroconjugation, but probably taurine's antioxidant, membrane stabilization (with Ca2+ and HCO3-), and/or osmotic effects.

Parenteral aluminum induces liver injury in a newborn piglet model

“…evidenced by loss of bile canaliculi microvilli and elevated serum bile acids. These findings mirror those reported in PNALD [12][13][14]. Bile acid transporter proteins, such as multidrug resistance protein, are located in the canaliculi microvilli and play an important role in bile acid metabolism.…”

Mitochondria-initiated apoptosis triggered by oxidative injury play a role in total parenteral nutrition–associated liver dysfunction in infant rabbit model

“…In the subsequent rabbit experiments by Loff [20], he confirmed that the histologic damage to the liver was obviously caused by the TPN solution itself, regardless of whether additional enteral feeding was also supplied. In another study of the relationship between taurine and TPN-associated cholestasis (TPN-AC) in rabbits, Moran and his colleagues [21] found that diffused liver steatosis, dilated canaliculi, abundant bile plugs, and loss of microvilli appeared after 10 days of TPN in rabbits. There were signs that taurine may protect against TPN-AC.…”

Plasma Levels of Conjugated Bile Acids in Newborns After a Short Period of Parenteral Nutrition

“…PN is associated with changes in plasma BA composition; the excess amounts of some BA cause hepatotoxic effects related to PN, and the administration of taurine can decrease the toxicity of BA. Conjugation of BA to taurine and glycine is mediated by the same competitive enzyme, 20 and in preterm infants, where the taurine is a provisionally essential amino acid, due to either an inability of endogenous synthesis or a nutrition deficit, conjugation of BA with glycine would be expected to increase. In fact, in the current study, GCA concentrations were significantly elevated in the T0 group (Table 2) as compared with healthy controls, which we attribute to the number of preterm infants in the T0 group (7/9).…”