Hepatic injury induced by bile salts: Correlation between biochemical and morphological events

Abstract

Continuous intravenous infusion of taurochenodeoxycholate at a rate of 0.4 mumol.min-1.100 gm-1 for only 30 min in rats caused threefold to tenfold greater release of proteins (alkaline phosphatase, lactate dehydrogenase and albumin) into bile in comparison with animals infused with tauroursodeoxycholate at much higher rates (1.8 mumol.min-1.100 gm-1) for 2 hr. The simultaneous infusion of tauroursodeoxycholate and taurochenodeoxycholate (0.6 and 0.4 mumol.min-1.100 gm-1, respectively) for 2 hr prevented the marked biochemical changes in the bile induced by taurochenodeoxycholate for 15 to 60 min exhibited significantly more necrotic hepatocytes, especially in zone 1, in comparison with animals infused with tauroursodeoxycholate or a combination of taurochenodeoxycholate and tauroursodeoxycholate. A good correlation was observed between biochemical and morphological indices of bile acid-induced hepatocyte injury. These data suggest that (a) primary events induced by the acute infusion of toxic bile salts responsible for cholestasis include zone 1 hepatocellular necrosis and (b) this can be prevented by the simultaneous infusion of tauroursodeoxycholate.

Obesity diabetes and the role of bile acids in metabolism

“…Deoxycholic acid modulates cell death through the changes in mitochondrial membrane properties. Cholestasis is associated with hepatitis and both hepatocyte and bile duct cell death through apoptosis, and in higher concentrations, by necrosis [5][6][7] . Deoxycholic acid is hydrophobic, but ursodeoxycholic acid, which is highly hydrophilic, inhibits apoptosis.…”

Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis

“…Retention and accumulation of toxic hydrophobic bile salts within the hepatocytes is partially responsible for the hepatocellular injury during cholestasis [3][4][5] . Other mechanisms have also been suggested to be involved.…”

Effects of bile acids on biliary epithelial cell proliferation and portal fibroblast activation using rat liver slices

“…During chronic cholestasis, bile acids may accumulate, particularly in hepatocytes, leading to histological abnormalities. 1 This occurs especially in childhood diseases such as biliary atresia, cystic fibrosis and paucity of interlobular bile ducts, 2 and also in the liver of adult patients suffering from chronic liver diseases. 3 Accumulation of toxic bile acids results in hepatocellular damage, ultimately leading to liver fibrosis and cirrhosis.…”