Affiliations: Rudjer Boskovic Institute, Zagreb, Croatia | Medical Faculty, Zagreb, Croatia
Note: [] Address for correspondence: Ana Cipak, Rudjer Boskovic
Institute, Division of Molecular Medicine, HR-10000 Zagreb, Bijenicka 54,
Croatia. Tel.: +385 1 457 1212; Fax: +385 1 456 1010; E-mail: acipak@irb.hr
Abstract: Liver regeneration is a complex, systemic process regulated by
humoral and cellular mechanisms. Inflammatory response to the extensive tissue
damage, as in partial hepatectomy, plays important role during regeneration.
Hence, it is assumed that the spleen might play a role in systemic inflammatory
response involved in liver regeneration. On the other hand, liver damage and
consequential regeneration are often associated with oxidative stress and lipid
peroxidation. One of the end products of lipid peroxidation, 4-hydroxynonenal
(HNE), is nowadays considered not only as a "second toxic messenger of free
radicals" but also as a growth-regulating factor. We therefore studied in
vitro interactions of the HNE-treated murine liver cells and autologous spleen
cells. The spleen cells supported recovery of liver cells from the HNE
cytotoxicity although spleen cells themselves exerted cytotoxic effects against
the proliferating liver cells that were not treated with HNE. Our results imply
that the cytokines secreted by activated immunocompetent cells may be
responsible for the observed recovery of the HNE-damage liver cells, suggesting
that HNE might be an important factor regulating cellular and cytokine mediated
mechanisms of liver regeneration control.
