Hepatic oval cells (OC) are considered to be the stem cells of the liver and have been linked to the development of hepatocellular carcinoma HCC, one of the most lethal cancers. The objective of this study was to analyse the proliferative response of OC obtained from rats receiving diethylnisamine DEN. In addition, we investigated the effects of resveratrol (Res) on the proliferation and oxidative markers of OC in vitro. OC isolated by in situ collagenase liver perfusion methods were treated with different concentrations of Res for 24, 48 and 72 hours. At the end of these periods the proliferative activity of OC, the release of superoxide anion by OC and the medium concentration of malonylodialdehyd were analyzed . The proliferation of OC cultured without Res increased from IP=0.945±0.02 to IP=1.525±0.031 after 24 and 72 hours respectively. A marked (p≤0.05) inhibition of OC proliferation was observed in the presence of 1.0 µM, 25 µM and 100 µM of Res. A significant decrease in the release of O2-. by OC, observed throughout the experimental period, was attributed to the presence of 25 µM of Res. Exposition of OC to 100 µM of Res inhibited the release of O2-. only after 48 and 72 hours of incubation. The presence of 25 µM of Res resulted in the depletion of MDA level, which did not exceed 0.19±0.009 nM. Proliferative activity of OC isolated from carcinogenic rats intensified throughout the culture period. When subjected to the carcinogenic effect of DEN, Res exerts anti-proliferative influence on OC. Moreover, our results provide evidence that Res attenuates oxidative stress during hepatocarcinogenesis.
SIGNIFICANCE OF STEM CELLS IN HEPATOCARCINOGENESIS IN RATS
GIORGI, MARIO;
2012-01-01
Abstract
Hepatic oval cells (OC) are considered to be the stem cells of the liver and have been linked to the development of hepatocellular carcinoma HCC, one of the most lethal cancers. The objective of this study was to analyse the proliferative response of OC obtained from rats receiving diethylnisamine DEN. In addition, we investigated the effects of resveratrol (Res) on the proliferation and oxidative markers of OC in vitro. OC isolated by in situ collagenase liver perfusion methods were treated with different concentrations of Res for 24, 48 and 72 hours. At the end of these periods the proliferative activity of OC, the release of superoxide anion by OC and the medium concentration of malonylodialdehyd were analyzed . The proliferation of OC cultured without Res increased from IP=0.945±0.02 to IP=1.525±0.031 after 24 and 72 hours respectively. A marked (p≤0.05) inhibition of OC proliferation was observed in the presence of 1.0 µM, 25 µM and 100 µM of Res. A significant decrease in the release of O2-. by OC, observed throughout the experimental period, was attributed to the presence of 25 µM of Res. Exposition of OC to 100 µM of Res inhibited the release of O2-. only after 48 and 72 hours of incubation. The presence of 25 µM of Res resulted in the depletion of MDA level, which did not exceed 0.19±0.009 nM. Proliferative activity of OC isolated from carcinogenic rats intensified throughout the culture period. When subjected to the carcinogenic effect of DEN, Res exerts anti-proliferative influence on OC. Moreover, our results provide evidence that Res attenuates oxidative stress during hepatocarcinogenesis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
