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


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 (IVM). Rats were divided into three groups: PDTC administration (group P), vehicle administration only (group C), 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 microm) were twice as large as those in group C (11.14 +/- 0.28 microm, P < 0.0001). This dilation of sinusoids was completely reversed by ZnPP (10.95 +/- 0.37 microm, P < 0.0001).


CONCLUSIONS
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.
Hata
Koichiro
K
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, 606-8507 Kyoto, Japan.
Yamamoto
Yuzo
Y
Nakajima
Akio
A
Taura
Kojiro
K
Yonezawa
Kei
K
Uchinami
Hiroshi
H
Ikeda
Fusao
F
Yamaoka
Yoshio
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology*; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000494:pharmacology*
D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1