title: [Possible role of biliverdin as an initiator of liver regeneration].
abstract: Biliverdin has been proposed as the biological signal that triggers liver regeneration after partial hepatectomy, since a transitory increase of plasma levels is found shortly after partial hepatectomy. We have carried out a detailed study to establish the feasibility of such a hypothesis. When biliverdin is administered i.p., it binds to albumin. This became evident by electrophoresis and affinity chromatography. Biliverdin disappears from the peritoneal cavity following a 1st order kinetics (t 1/2 = 40 min, K = 0.0175 min -1). Biliverdin reductase activity in the peritoneal exudate was high (1.04 mumol Bv min -1/mg protein), and very small amounts of biliverdin in comparison to the administered dose were found in plasma. However, unconjugated bilirubin level was high in plasma and the conjugated bilirubin in bile flux reached its maximum 90 min after administration. On the basis of blood elimination of biliverdin when administered intravenously (t 1/2 = 11 min, K = 0.068 min -1), a series of experiments was designed to reproduce the levels of plasma biliverdin as found shortly after partial hepatectomy. Our results showed a total absence of liver regeneration. There is, however, increase of the mitotic index if biliverdin is administered intraperitoneally. This effect is not directly related to biliverdin but to unspecific (?) stimulation of peritoneal cavity since the same effect was obtained after administration of unrelated substances (diatomaceous earth, killed bacteria). The mitotic figures did not incorporate 3H-thymidine, and it is suggested that those cells came from a G2 blocked quiescent cell population in liver. We therefore conclude that biliverdin is not the physiological trigger of liver regeneration.
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D001663:Bilirubin / Q000031:analogs & derivatives*; D001664:Biliverdine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D006498:Hepatectomy; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects; D008115:Liver Regeneration; D008940:Mitotic Index / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000418:Albumins; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase; D001664:Biliverdine; D001663:Bilirubin
vernacular_title: Posible papel de la biliverdina como iniciador de la regeneración hepática.