Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

  • V. Bertone University of Pavia, Italy.
  • E. Tarantola University of Pavia, Italy.
  • A. Ferrigno University of Pavia, Italy.
  • E. Gringeri University of Padua, Dept of Surgical and Gastroenterological Sciences P.G. Cevese, Italy.
  • S. Barni University of Pavia, Italy.
  • M. Vairetti University of Pavia, Italy.
  • I. Freitas | University of Pavia, Italy.


Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT). Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS). However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20) that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC, frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but most hepatocytes were devoid of AlkP activity with the exception of clusters of macrosteatotic hepatocytes in the mid-zone, where the reaction was intense in basolateral domains and in distorted canaliculi, a typical pattern of cholestasis. The interpretation of these data was hindered by the fact that the physiological role of AlkP is still under debate. In the present study, the various functions proposed for the role of the enzyme in bile canaliculi and in cholangiocytes are reviewed. Independently of the AlkP role, our data suggest that AlkP does not seem to be a reliable marker to study the initial step of bile production during OLT of fatty livers, but may still be used to investigate the behaviour of bile ductules and small bile ducts.


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Author Biographies

V. Bertone, University of Pavia
Researcher at Animal Biology Department
E. Tarantola, University of Pavia
PhD Student
A. Ferrigno, University of Pavia
PhD Student
E. Gringeri, University of Padua, Dept of Surgical and Gastroenterological Sciences P.G. Cevese
S. Barni, University of Pavia
full Professor
M. Vairetti, University of Pavia
I. Freitas, University of Pavia
Associate Professor
Original Papers
Supporting Agencies
This research was supported by MIUR-PRIN (Ministero dell’Università e Ricerca, Progetti di Rilevante Interesse Nazionale) 2004 and 2006 and by F.A.R. (Fondi di Ateneo per la Ricerca), University of Pavia, Italy
biliary tract, alkaline phosphatase, fatty liver, cholestasis, bile canaliculi, hepatocytes, cholangiocytes.
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How to Cite
Bertone, V., Tarantola, E., Ferrigno, A., Gringeri, E., Barni, S., Vairetti, M., & Freitas, I. (2011). Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme. European Journal of Histochemistry, 55(1), e5.