Abstract
Macroscopic and microscopic types of peliosis hepatis, time pattern, and correlation with hepatocyte and sinusoidal cell apoptosis were investigated. Male Wistar rats were injected with a dose of cadmium (6.5 mg CdCl2/kg body weight, intraperitoneally; group I). Putrescine (300 μmol/kg body weight, intraperitoneally; group II) was injected at 2, 5, and 8 hours and vascular endothelial growth factor (VEGF; 400 ng/animal, intravenously; group III) at 2 hours. Animals from each group were humanely killed 0, 6, 12, 24, 48, or 60 hours after cadmium intoxication. Liver tissue was histologically assessed for necrosis, apoptosis, and peliosis. Apoptosis was also quantified by the TUNEL assay for hepatocytes and nonparenchymal liver cells. The discrimination between hepatic cell subpopulations was done histochemically. Sinusoidal cell apoptosis and macroscopic peliosis hepatis evolved in a monophasic pattern and correlated closely. Putrescine or VEGF administration totally reversed macroscopic peliosis. Putrescine exerted a major protective effect on hepatocytes, whereas the protective effect of VEGF was more pronounced for nonparenchymal liver cells. Microscopic peliosis also evolved in a monophasic pattern preceding macroscopic type. The extent of the lesion was reduced by putrescine and almost totally reversed by VEGF. Macroscopic peliosis progresses as a compound lesion closely correlating with nonparenchymal cell apoptosis. Both hepatocyte and nonparenchymal cell injury are prerequisites for the genesis of the lesion. Microscopic peliosis precedes macroscopic peliosis and up to a degree seems to be independent of initial hepatocyte injury, but it seems to depend on nonparenchymal cell injury.
Similar content being viewed by others
References
Zak FG (1950) Peliosis hepatis. Am J Pathol 26:1–15
Wold LE (1981) Peliosis hepatis: Two morphological variants? Hum Pathol 12:388–389
Kubosawa H, Konno A, Komatsu T, Ishige H, Kondo Y (1989) Peliosis hepatis: An unusual case involving the spleen and lymph nodes. Acta Pathol Jpn 39:212–215
Zafrani ES (1990) An additional argument for a toxic mechanism of peliosis hepatis in man. Hepatology 11:322–323
Yanoff M, Rawson AJ (1964) Peliosis hepatis: An anatomic study with demonstration of two varieties. Arch Pathol 77:159–165
Zafrani ES, Degos F, Guigui B, Durand-Schneider AM, Martin N, Flandrin G, Benhaman JP, Feldmann G (1987) The hepatic sinusoid in hairy cell leukaemia: An ultrastructural study of 12 cases. Hum Pathol 18:801–807
Bhaskar KV, Joshi K, Banerjee CK, Rao RK, Verma SC (1990) Peliosis hepatis in Hodgkin's disease: An infrequent association. Am J Gastroenterol 85:628–629
Cadranel JF, Cadranel J, Buffet C, Fabre M, Pelletier G, d’Agay MF, Ink O, Roche A, Milleron B, Etienne JP (1990) Nodular regenerative hyperplasia of the liver, peliosis hepatis, and perisinusoidal fibrosis: Association with angioimmunoblastic lymphadenopathy and severe hypoxemia. Gastroenterology 99:268–273
Hayward SR, Lucas CE, Ledgerwood AM (1991) Recurrent spontaneous intrahepatic hemorrhage from peliosis hepatis. Arch Surg 126:782–783
Habeebu SS, Liu J, Klaassen CD (1998) Cadmium-induced apoptosis in mouse liver. Toxicol Appl Pharmacol 149:203–209
Tzirogiannis KN, Panoutsopoulos GI, Demonakou MD, Hereti RI, Alexandropoulou KN, Basayannis AC, Mykoniatis MG (2003) Time-course of cadmium-induced acute hepatotoxicity in the rat liver: The role of apoptosis. Arch Toxicol 77:694–701
McSween R, Bart A, Portman B, Ishak K, Schewer B, Antony P (eds) (2002) Pathology of the liver, 4th edn. Churchill Livingstone, New York
Fowler BA (1991) Other toxic effects. In: Friberg L, Elinder CG, Kjellstrom T, Nordberg GF (eds) Cadmium and health: A toxicological and epidemiological appraisal. CRC Press, Boca Raton, FL, pp 159–204
Kotsonis FN, Klaassen CD (1977) Toxicity and distribution of cadmium administered to rats at sublethal doses. Toxicol Appl Pharmacol 41:667–680
Dudley RE, Svoboda DJ, Klaassen C (1982) Acute exposure to cadmium causes severe liver injury in rats. Toxicol Appl Pharmacol 65:302–313
Dudley RE, Svoboda DJ, Klaassen CD (1984) Time-course of cadmium-induced ultrastructural changes in rat liver. Toxicol Appl Pharmacol 76:150–160
Kayama F, Yoshida T, Elwell MR, Luster MI (1995) Role of tumor necrosis factor-alpha in cadmium-induced hepatotoxicity. Toxicol Appl Pharmacol 131:224–234
Dong W, Simeonova PP, Gallucci R, Matheson J, Flood L, Wang S, Hubbs A, Luster MI (1998) Toxic metals stimulate inflammatory cytokines in hepatocytes through oxidative stress mechanisms. Toxicol Appl Pharmacol 151:359–366
Rikans LE, Yamano T (2000) Mechanisms of cadmium-mediated acute hepatotoxicity. J Biochem Mol Toxicol 14:110–117
Yamano T, Shimizu M, Noda T (1998) Age-related change in cadmium-induced hepatotoxicity in Wistar rats: Role of Kupffer cells and neutrophils. Toxicol Appl Pharmacol 151:9–15
Yamano T, DeCicco LA, Rikans LE (2000) Attenuation of cadmium-induced liver injury in senescent male Fischer 344 rats: Role of Kupffer cells and inflammatory cytokines. Toxicol Appl Pharmacol 162:68–75
Heby O (1981) Role of polyamines in the control of cell proliferation and differentiation. Differentiation 19:1–20
Tabor CW, Tabor H (1984) Polyamines. Annu Rev Biochem 53:749–790
Schuber F (1989) Influence of polyamines on membrane functions. Biochem J 260:1–10
Ballas SK, Mohandas N, Marton LJ, Shohet SB (1983) Stabilization of erythrocyte membranes by polyamines. Proc Natl Acad Sci U S A 80:1942–1946
Igarashi K, Kashiwagi K (2000) Polyamines: Mysterious modulators of cellular functions. Biochem Biophys Res Commun 271:559–564
Nishiguchi S, Kuroki T, Takeda T, Nakajima S, Shiomi S, Seki S, Matsui-Yuasa I, Otani S, Kobayashi K (1990) Effects of putrescine on D-galactosamine-induced acute liver failure in rats. Hepatology 12:348–353
Nagoshi S, Ohta Y, Matsui A, Fujiwara K (1994) Protective action of putrescine against rat liver injury. Scand J Gastroenterol 29:166–171
Tanigushi E, Sakisaka S, Matsuo K, Tanikawa K, Sata M (2001) Expression and role of vascular endothelial growth factor in liver regeneration after partial hepatectomy in rats. J Histochem Cytochem 49:121–129
Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22
Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25
Moriga T, Arii S, Takeda Y, Furuyama H, Mizumoto M, Mori A, Hanaki K, Nakamura T, Fujioka M, Imamura M (2000) Protection by vascular endothelial growth factor against sinusoidal endothelial damage and apoptosis induced by cold preservation. Transplantation 69:141–147
Yamane A, Seetharam L, Yamaguchi S, Gotoh N, Takahashi T, Neufeld G, Shibuya M (1994) A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1). Oncogene 9:2683–2689
Katoh O, Tauchi H, Kawaishi K, Kimura A, Satow Y (1995) Expression of the vascular endothelial growth factor(VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation. Cancer Res 55:5687–5692
Nor JE, Christensen J, Mooney DJ, Polverini PJ (1999) Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. Am J Pathol 154:375–384
Gupta K, Kshirsagar S, Li W, Gui L, Ramakrishman S, Gupta P, Law PY, Hebbel RP (1999) VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp Cell Res 247:495–504
Ishikawa K, Mochida S, Mashiba S, Inao M, Matsui A, Ikeda H, Ohno A, Shibuya M, Fujiwara K (1999) Expressions of the vascular endothelial growth factor in nonparenchymal as well as parenchymal cells in rat liver after necrosis. Biochem Biophys Res Commun 254:587–593
Mochida S, Ishikawa K, Inao M, Shibuya M, Fujiwara K (1996) Increased expressions of vascular endothelial growth factor and its receptors, flt-1 and KDR/flk-1, in regenerating rat liver. Biochem Biophys Res Commun 226:176–179
Assy N, Spira G, Paizi M, Shankar L, Kraizer Y, Cohen T, Neufield G (1998) Effect of vascular endothelial factor on hepatic regenerative activity following partial hepatectomy in rats [Abstract]. Hepatology 28:522A
Ankoma-Sey V, Matli M, Chang KB, Lalazar A, Donner DB, Wong L, Warren RS, Friedman SL (1998) Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing. Oncogene 17:115–121
Greek presidential decree No 160/1991 (1991) Protection of animals used for experimental and other scientific purposes in accordance with EU Directive 86/609/EEC of the Council. Governmental Gazette No 64
Motoyama S, Minamiya Y, Saito S, Saito R, Matsuzaki I, Abo S, Inaba H, Enomoto K, Kitamura M (1998) Hydrogen peroxide derived from hepatocytes induces sinusoidal cell apoptosis in perfused hypoxic rat liver. Gastroenterology 114:153–163
Tzirogiannis KN, Panoutsopoulos GI, Demonakou MD, Papadimas GK, Kondyli VG, Koutentzi KT, Hereti RI, Mykoniatis MG (2004) The hepatoprotective effect of putrescine against cadmium-induced acute liver injury. Arch Toxicol 78:321–329
Haboubi NY, Ali HH, Whitwell HL, Ackrill P (1988) Role of endothelial cell injury in the spectrum of azathioprine-induced liver disease after renal transplant: Light microscopy and ultrastructural observations. Am J Gastroenterol 83:256–261
Nadell J, Kosek J (1977) Peliosis hepatis: Twelve cases associated with oral androgen therapy. Arch Pathol Lab Med 101:405–410
Urabe M, Kawasaki H, Takasaki K (1991) Effect of endothelium removal on the vasoconstrictor response to neuronally released 5-hydroxytryptamine and noradrenaline in the rat isolated mesenteric and femoral arteries. Br J Pharmacol 102:85–90
Morcos NC, Grandaw PP, Henry WL, Purdy RE (1991) Modulation of serotonin-induced vasospasm by endothelium and monoamine oxidase. Int J Tissue React 13:19–26
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tzirogiannis, K.N., Papadimas, G.K., Kondyli, V.G. et al. Peliosis Hepatis: Microscopic and Macroscopic Type, Time Pattern, and Correlation With Liver Cell Apoptosis in a Model of Toxic Liver Injury. Dig Dis Sci 51, 1998–2006 (2006). https://doi.org/10.1007/s10620-006-9242-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-006-9242-x