Hepatic injury induced by bile salts: Correlation between biochemical and morphological events
✍ Scribed by Douglas L. Schmucker; Minoru Ohta; Setsuko Kanai; Yuko Sato; Kenichi Kitani
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 685 KB
- Volume
- 12
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
Continuous intravenous infusion of taurochenode-
oxycholate at a rate of 0.4 pmol * min -' -100 gm-' 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 pmolmin-' 100 gm-') for 2 hr. The simultaneous infusion of tauroursodeoxycholate and taurochenodeoxycholate (0.6 and 0.4 pmol * min-' * 100 gm-', respectively) for 2 hr prevented the marked biochemical changes in the bile induced by taurochenodeoxycholate infusion alone. Livers infused with 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 iqjury. 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 (HEP-ATOLOGY 1990;12: 1216-122 1.)
Although most bile salts induce acute hepatocytic injury accompanied by reduced bile flow (cholestasis) when administered in large doses, the evidence for a morphologcal correlate to these physiological and biochemical alterations is sparse. Hardison et al. (1) reported minimal histological abnormalities associated with marked biochemical changes and cholestasis in the livers of rats subjected to bile salt infusions. The random distribution of necrotic hepatocytes observed by these investigators may contribute to the cause of hepatobiliary dysfunctions, but the absence of quantitative morphological data precludes any definitive interpretations. We previously reported that taurochenodeoxycholate (TCDC) and taurocholate (TC) infusions cause