Induction of heme oxygenase-1 and dilatation of hepatic sinusoids by an administration of pyrrolidine dithiocarbamate in rat livers

Introduction. Inducing heme oxygenase-1 (HO-1) provides the liver with various protective effects against stressful conditions. In this article, we report our use of pyrrolidine dithiocarbamate (PDTC) to induce HO-1 in the liver in vivo and its impact on hepatic microcirculation. Materials and methods. PDTC was injected intramuscularly into rats and the expression of HO-1 in liver tissue was assessed by measuring both mRNA and protein levels. The distribution of induced HO-1 was evaluated immunohistochemically. The effect of PDTC administration on hepatic microcirculation was evaluated using intravital. microscopy (PVM). Rats were divided into three groups: PDTC administration (group P), vehicle administration only (group Q, and ZnPP-an inhibitor of HO-1-administration after PDTC treatment (group Z). Sinusoidal diameters were measured 24 h after the injections. Results. PDTC administration induced HO-1 strongly in the liver, but not in other organs. HO-1 mRNA expression in liver tissue peaked 3 h after PDTC injection and then gradually decreased. The protein expression reached a maximum level at 24-48 h after the injection, and its expression was dose-dependent with PDTC. Immunohistochemistry revealed that HO-1 was induced not only in Kupffer cells, but also in hepatocytes in the pericentral area. IVM showed that in group P, sinusoidal diameters in zone 3 (21.94 +/- 1.29 mum) were twice as large as those in group C (11.14 +/- 0.28 mum, P < 0.0001). This dilation of sinusoids was completely reversed by ZnPP (10.95 +/- 0.37 mum, P < 0.0001). Conclusion. A single administration of PDTC induced HO-1 in the liver with remarkable sinusoidal dilation. PDTC administration, therefore, may be a useful, new strategy in place of other stress preconditioning. (C) 2003 Elsevier Inc. All rights reserved.