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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 91, Num. 6, 1996
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Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 91(6),
Nov./Dec. 1996,
RESEARCH NOTE
Influence of the Route of Administration of Pig-serum in
the Induction of Hepatic Septal Fibrosis in Rats
Zilton A Andrade/+, Adriana Godoy*
Laboratorio de Patologia Experimental, Centro de Pesquisas
Goncalo Moniz-FIOCRUZ, Rua Valdemar Falcao 121, 40945-001
Salvador, BA, Brasil
+Corresponding author. Fax: +55-71-359.4292
*Fellow, Brazilian National Research Council (CNPq)
Received 10 April 1996, Accepted 25 June 1996
Code Number: OC96141
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Key words: liver - septal fibrosis - fibrogenesis - pig-
serum model
Repeated intraperitoneal injections of pig-serum into rats
result in the production of hepatic septal fibrosis (F
Paronetto & H Popper 1966 Am J Pathol 40: 1087-1101).
This is an interesting model of liver fibrosis that occurs
without previous liver-cell necrosis or inflammation (E Rubin
et al. 1968 Am J Pathol 52: 111-119). Its pathogenesis
primarily involves the sinusoidal Kupffer cell/perisinusoidal
Ito-cell axis, which is activated by so-called fibrogenic
cytokines (AM Gressner & MG Bachem 1990 Sem Liver Dis
10: 30-46, EJ Kovacs 1991 Immunol Today 12: 17-23).
Recently septal fibrosis of the liver was detected as an
important manifestation of Capillaria hepatica
infection in rats (LA Frerreira & ZA Andrade 1993 Mem Inst
Oswaldo Cruz 88: 441-447). This finding, as well as
similar ones seen in schistosomiasis (AW Cheever & Andrade ZA
1970 Gaz Med Bahia 70: 67-74) and fascioliasis (JD
Dargie et al. 1974 Parasitic Zoonoses, Clinical and
Experimental Studies, Academic Press, New York) are
suggestive that antigens being slowly liberated within the
liver itself would be more readily available to the hepatic
intra and peri-sinusoidal fibrogenic system. Thus, the closer
the appropriate antigen releasing is to the liver, the more
effective would be its ability to induce septal fibrosis.
Actually little is known about the influence of the route of
antigen administration for the experimental generation of
septal fibrosis of the liver. To investigate this subject two
different routes of antigen administration were investigated
during the production of pig-serum induced septal fibrosis of
the liver in rats. Twenty Wistar rats were used. They were of
both sexes, weighing 170/300g, maintained in separate cages
with a commercial balanced diet and water ad libitum.
Pig blood was collected from several animals in a slaughter
house. After coagulation it was immediately centrifuged for
the collection of serum, which was stored in small vials at
4oC. Electrophoresis of pig-serum revealed: albumin: 48.7%,
a1: 0.5%, a2: 20.0%, b1: 3.0%, b2: 4.5% and g: 23.3%. It has
been determined that the albumin fraction is the one mainly
related to the fibrogenic activity of the pig-serum in rats
(Paronetto & Popper loc. cit.). Serum injections were
made twice a week for a total of 26 injections. Half of the
animals was injected intraperitoneally and the other half
subcutaneously in the dorsal region. All animals completed the
entire treatment period without losing weight or showing any
external sign of disease. Observation of fibrosis was
performed in sections from the liver taken after autopsy of
the animals. Fragments of the liver were fixed in pH 7.4
buffered 10% formalin, embedded in paraffin and the sections
stained with hematoxylin and eosin, the picro-sirius-red
method for collagen and the Gomori silver impregnation method
for reticulum. Grossly there was only a mild thickening of the
external capsule and a slight increase in consistency in a few
of the livers taken from the intraperitoneally-injected
animals. Microscopically, septal fibrosis, represented by
fine, long and straight lines of fibrous tissue located along
the zone III of the hepatic acinus was detected in 42.8% of
the animals intraperitoneally injected with pig-serum. In the
other animals of this same group variable degrees of
perisinusoidal thickening and of hyperplasia of reticulin
fibrils were detected in all but two of them.
The livers of the animals injected into the subcutaneous
dorsal region with pig-serum were essentially normal and not
even perisinusoidal reticulin increase was detected in them.
Thus, clear-cut results pointed to the influence of the route
of administration of pig-serum in the experimental production
of septal liver fibrosis in rats. Reasons for this have not
been determined. Of course it is not merely a question of a
distance to be traveled by the factor(s) in the pig-serum, but
may involve a host of complex influences, one of them being
differences in the kind of local antigen-presenting cells and
the way local tissues process foreign material. The presence
of septal fibrosis in 40% of the animals injected by the
intraperitoneal route represents the usual percentage obtained
by others with the rat pig-serum model (K Fujiwara et al. 1988
Hepatology 8: 804-807, ZA Andrade 1991 Int J Exp
Path 72: 551-562).
Copyright 1996 Fundacao Oswaldo Cruz
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