engleski

4-hydroxynonenal and splenic cells modify in vitro growth of rat hepatocytes

Although 4-hydroxynonenal (HNE) was first identified as highly cytotoxic product of lipid peroxidation, now it is believed that HNE is also cell growth modifier that plays role in signaling. Our previous results showed that spontaneously immortalized murine liver cells pretreated in vitro with cytotoxic concentration of HNE recover only if they are cultivated with spleen cells. One the other hand, oxidative stress was shown to play regulatory role during liver regeneration, while splenic cells infiltrate regenerating liver cells also having certain, not yet explained role in regulation of the liver regeneration. Hence, we wanted to see if this phenomenon would be repeated with cultured hepatocytes. For this purpose we have isolated hepatocytes from adult Fisher rat by the in situ two-step collagenase perfusion technique. Hepatocytes were treated with 1 &micro ; M and 10 &micro ; M HNE and were cultivated either with or without spleen cells. Cells were stained with DAPI, and then analyzed for micronuclei, mitotic index, apoptosis and necrosis. There were no differences if hepatocytes were treated with 1 &micro ; M HNE, nor if they were cultivated alone or with spleen cells. However, if hepatocytes treated with 10 &micro ; M HNE were co-cultivated with splenic cells, they showed significantly less apoptosis and necrosis then hepatocytes treated with 10 M only. These findings indicate possible novel regulatory mechanism of liver regeneration.

4-hydroxynonenal; hepatocytes; splenic cells

nije evidentirano