Uridine diphosphoglucose restores lipocyte proliferation in the regenerating liver of ethanol-treated rats

Abstract

The effect of continuous intraperitoneal infusion of undine diphosphoglucose on ethanlol-induced suppression of lipocyte proliferation was studied in regenerating rat livers from 1–4 days after hepatectomy. Proliferating lipocytes were positively identified using a two-sequence immunohistochemical staining for cytoplasmic desmin and bromodeoxyuridine-labelled nuclei. Hepatectomy rapidly stimulated lipocyte proliferation which peaked 2 days after hepatectomy (labelling index, 17.9 ± 0.81%). uridine diphosphoglucose or glucose infusion did not modify the time course of lipocyte proliferation. Ethanol feeding to hepatectomized rats receiving saline or glucose infusion resulted in a 71% ( p < 0.005) and 61% ( p < 0.005) inhibition of lipocyte proliferation, respectively, 2 days after hepatectomy, thereby abolishing the characteristic proliferative peak observed in rats not treated with ethanol. In contrast, uridine diphosphoglucose infusion doubled the labelling index (13.1 ± 2.34%) in ethanol-fed rats compared to that in corresponding rats treated with saline (5.28 ± 1.29%; p < 0.005) or glucose (6.51 ± 0.64%; p < 0.005). This resulted in the appearance of a proliferative peak, albeit smaller than normal, 2 days after hepatectomy. In sham-operated rats, lipocyte proliferation was low with a labelling index of 1.88 ± 0.13% at the time of operation and of 1.69 ± 0.23% 2 days thereafter. Uridine diphosphoglucose infusion to sham-operated rats for 2 days did not significantly affect lipocyte proliferation (labelling index 1.79 ± 0.06%). The present study demonstrated that uridine diphosphoglucose does not affect lipocyte proliferation in the regenerating or sham-operated livers, but that it partially reverses the ethanol-induced suppression of lipocyte proliferation after hepatectomy.