Adaptive hepatic changes in mild stenosis of the common bile duct in the rat

Abstract

Adaptive hepatic changes were investigated in rats with mild stenosis of the common bile duct and in sham-operated controls. The studies were performed 24 h and 7-12 days postoperatively. A continuous intravenous infusion of taurocholic acid at stepwise-increasing rates was performed to explore the responses to bile acid effects. During the infusion, bile flow and the outputs of bile acids, phospholipids, cholesterol, alkaline phosphatase and gamma glutamyl transpeptidase were studied. At the end of the infusion, hepatic morphometric measurements were performed. In other experimental sets, biliary excretions of horseradish peroxidase, a marker of microtubule-dependent vesicular transport in the hepatocyte, and sulphobromophthalein, a well-known organic anion model, were studied. In other rats, bile acid pool size and composition were determined by depletion of bile. The results in rats with mild stenosis maintained for 24 h showed a greater susceptibility to the toxicity of taurocholic acid, as revealed by the abrupt decrement in bile flow at high rates of infusion, and increased outputs of phospholipids and canalicular enzymes. Conversely, rats with mild stenosis maintained for 7-12 days showed decreased bile acid maximum secretory rate and biliary outputs of phospholipids and canalicular enzymes, as well as hepatocyte hypertrophy. These findings may explain the limited hepatic and systemic repercussion of experimental mild stenosis of the common bile duct and help us to understand the early stages of constriction of the common bile duct in man.

Inhibitory Effect of Short-Term Bile Duct Ligation on Hepatic Cytochrome P450 of Bile Acid-Depleted Rats

“…Preliminary experiments indicated that the bile acid pool size in the rat was about 30 Ìmol/ 100 g body weight, which is in agreement with previous data [24]. When bile acid-depleted rats were replenished with such an amount of TC, this was completely recovered in the bile collected during 80 min.…”

“…In this study we used normal rats that were depleted of endogenous bile acids and then replenished with TC, and considered a toxic bile acid which is in turn the major hepatic bile acid found in the rat at the completion of biliary drainage [15,24]. Preliminary experiments indicated that the bile acid pool size in the rat was about 30 Ìmol/ 100 g body weight, which is in agreement with previous data [24].…”

Swimming Attenuates Muscle Wasting and Mediates Multiple Signaling Pathways and Metabolites in CT-26 Bearing Mice

“…Among them, taurfodeoxycholic acid plays an important role in anti-inflammatory effects through the TGR5 receptor-induced cAMP-PKA-CREB signaling pathway, specifically by activating kappa light chain enhancer in B cells, reducing the activities of TNF-α, IL-1β and IL-6 ( Qi et al, 2020 ). Taurocholic acid not only exhibits the effects of anti-inflammation, lowering blood pressure, and reducing the amplitude and frequency of cardiac contraction ( Taranto et al, 2001 ), it is also involved in immune response by directly inhibiting the apoptosis of immune cells at different stages ( Schwarz et al, 1975 ; Rodriguez-Garay et al, 1999 ). Ascorbic acid is a hexacarboxylate, also known as vitamin C, was involved in inhibiting the growth of HCT116 cells in mice, prolonging the survival rate of CRC patients, enhancing the sensitivity of colorectal cancer to chemotherapy, and reducing the adverse reactions of radiotherapy and chemotherapy ( Siegel et al, 2014 ; Roncucci and Mariani, 2015 ).…”

Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment

“…For example, rats with mild hepatic stenosis have an approximate 15% reduction in basal bile flow when compared with control animals [45]. One animal model in which biliary function has been quantitatively examined is liver dysfunction induced by the subchronic to chronic administration of TPN, an intravenous diet given in severe cases of GI disorders.…”