OBJECTIVETo probe the effects of long-term oral administration of lanthanum nitrate [La(NO(3))(3)] on morphological change in the liver, aftereffect of deposited La in the liver and their mechanism in rats.

METHODSYoung Wistar rats were divided into two groups, one fed with 0.1, 0.2, 2.0, 10.0 and 20.0 mg/kg of La(NO(3))(3) for six months and the other for the control. Changes in ratio of liver to body weight were observed after exposure to La(NO(3))(3) at varied doses for six months and one month after six-month exposure, as well as morphology of the liver in the rats with routine histochemistry and transmission electron microscopy (TEM) technique. Content of La in the liver was measured with inductively coupled plasma-mass spectrometry (ICP-MS).

RESULTSRatio of liver to body weight was significantly higher in the male rats exposed to 20.0 mg/kg of lanthanum for six months than that in the control group. Ratio of liver to body weight restored to normal in the rats exposed to 20.0 mg/kg of La one month after six-month exposure. Infiltration of inflammatory cells in the portal region of the liver, small amount of fat drops in hepatocytic cytoplasm, increased density of mitochondria stroma, lysosome containing highly-electronic-density bodies and dense granules, normal nucleus and slightly deformed nucleus of hepatocytes could be found in the rats exposed to 20.0 mg/kg. Areas of the liver deposited with glycogen after six-month exposure to 20.0 mg/kg of La accounted for (26.1 +/- 1.5)% and (4.1 +/- 1.4)%, respectively for male and female rats, significantly lower than those in the control group [(31.3 +/- 1.4)% and (39.4 +/- 0.9)%, respectively], with a statistical significance and very statistical significance, respectively. There was a little infiltration of inflammatory cells in the portal region of the liver one month after six-month exposure to 20.0 mg/kg of La, and amount of the dense bodies was lower in the rats exposed to La for six months. Liver contents of La in the rats of all experimental groups were lower one month after six-month exposure than those in the rats exposed for six months.

CONCLUSIONSExposure to a dose of 20.0 mg/kg La(NO(3))(3) for a long term could damage the liver structure to certain extent, but lanthanum deposited in the liver could be eliminated from the body gradually.

Administration, Oral ; Animals ; Female ; Lanthanum ; toxicity ; Liver ; drug effects ; metabolism ; pathology ; Male ; Organ Size ; Rats ; Rats, Wistar

OBJECTIVETo explore the effects of ytterbium citrate on human liver carcinoma HepG2 cell line and the potential mechanisms.

METHODSThe HepG2 cells were cultured with DMEM medium and divided into different groups in the following media, in serum-free medium as control, different concentration (0.01 - 5.00 mmol/L) [YbCit(2)](3-)+serum-free medium as treatment group, MTT assay was used to measure the viability of the cells; 2.00 mmol/L [YbCit(2)](3-)+serum-free medium was used as treatment group, and Hoechst 33258 staining was used to detect apoptosis in HepG2 cells. Differential proteomic analysis, assay of intracellular H(2)O(2) levels and mitochondrial transmembrane potential were performed to study the effects of [YbCit(2)](3-) on HepG2 cells and the potential mechanisms.

RESULTSThe data showed that 72 h treatment of [YbCit(2)](3-) at 2.00 - 5.00 mmol/L significantly inhibited cell proliferation, and the IC(50) was (2.46 ± 0.23) mmol/L. After treatment with 2.00 mmol/L [YbCit(2)](3-) for 48 h and 72 h, Hoechst 33258 staining demonstrated that [YbCit(2)](3-) induced significantly increased apoptosis in HepG2 cells. After treatment with 2.00 mmol/L [YbCit(2)](3-) for 72 h, two dimensional gel electrophoresis and MALDI-TOF mass spectrometry analysis revealed 14 differentially expressed proteins between [YbCit(2)](3-)-treated cells and the control cells. These proteins mainly included cofilin1, peroxiredoxin6, S100 calcium-binding protein A6, and proteasome 26S non-ATPase subunit 13 isoform 3 and so on. These proteins played important roles in the processes of anti-apoptosis, oxidation reduction, cell proliferation and protein degradation. The mitochondrial membrane potential were investigated, the results showed the red and green fluorescence ratio was 2.45 ± 0.28 in the control group, 1.56 ± 0.23 in 24 h group, 1.16 ± 0.18 in 48 h group, compared with the control, the differences were significant (F = 23.97, P = 0.001). The results of H(2)O(2) detection showed the fluorescence intensity was 20.00 ± 2.08 in the control group, 40.00 ± 5.50 in 24 h group, and 48.00 ± 2.03 in 48 h group, compared with the control, the differences were significant (F = 48.40, P = 0.000). The results indicated a significant reduction in mitochondrial transmembrane potential and significant increase in H2O2 generation were observed in [YbCit(2)](3-)-treated cells.

CONCLUSIONThese results suggested that [YbCit(2)](3-) could induce apoptosis of HepG2 cells through the mechanisms involving oxidative stress and mitochondrial dysfunction.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Membrane Potential, Mitochondrial ; drug effects ; Oxidative Stress ; Proteome ; analysis ; Proteomics ; Ytterbium ; pharmacology