Protective effect of selenium-enriched Lactobacillus on CCl4-induced liver injury in mice and its possible mechanisms.
OBJECTIVE
To study the protective effects and mechanisms of Se-enriched lactobacillus on liver injury caused by carbon tetrachloride (CCl4) in mice.


METHODS
Seventy-two ICR mice were randomly divided into four groups: normal group, CCl4-induced model group, low Se-enriched lactobacillus treatment group (L-Se group), and high Se-enriched lactobacillus treatment group (H-Se group). During a 3-wk experimental period, the common complete diet was orally provided daily for normal group and model group, and the mice in L-Se and H-Se groups were given a diet with 2 and 4 mg of organoselenium from Se-enriched lactobacillus per kg feed, respectively. From the 2nd wk of experiment, the model group, L-Se group, and H-Se group received abdominal cavity injection of olive oil solution containing 500 mL/L CCl4 (0.07 mL/100 g body mass) to induce liver injury, and the normal group was given olive oil on every other day for over 2 wk. In the first 2 wk post injection with CCl4, mice in each group were killed. The specimens of blood, liver tissue, and macrophages in abdominal cavity fluid were taken. Then the activities of the following liver tissue injury-associated enzymes including glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as malondialdehyde (MDA) content were assayed. Changes of phagocytic rate and phagocytic index in macrophages were observed with Wright-Giemsa stain. Plasma TNF-alpha level was measured by radioimmunoassay. The level of intracellular free Ca2+ ([Ca2+]i) in hepatocytes was detected under a laser scanning confocal microscope.


RESULTS
During the entire experimental period, the AST and ALT activities in liver were greatly enhanced by CCl4 and completely blunted by both low and high doses of Se-enriched lactobacillus. The Se-enriched lactobacillus-protected liver homogenate GSH-Px and SOD activities were higher or significantly higher than those in model group and were close to those in normal group. CCl4 significantly increased MDA content in liver homogenates, while administration of Se-enriched lactobacillus prevented MDA elevation. Phagocytic rate and phagocytic index of macro-phages decreased after CCl4 treatment compared to those in normal control, but they were dramatically rescued by Se-enriched lactobacillus, showing a greatly higher phagocytic function compared to model group. CCl4 could significantly elevate plasma TNF-alpha and hepatocyte [Ca2+]i level, which were also obviously prevented by Se-enriched lactobacillus.


CONCLUSIONS
Se-enriched lactobacillus can intervene in CCl4-induced liver injury in mice by enhancing macrophage function activity to keep normal and beneficial effects, elevating antioxidant-enzyme activities and reducing lipid peroxidation reaction, inhibiting excessive release of TNF-alpha, preventing the dramatic elevation of [Ca2+]i in hepatocytes.
Chen
Long
L
College of Life Sciences, Nanjing Normal University, Nanjing 210097, Jiangsu Province, China. lchen@njnu.edu.cn
Pan
Dao-Dong
DD
Zhou
Juan
J
Jiang
Ying-Zi
YZ
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000517:prevention & control; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007778:Lactobacillus / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000473:pathology / Q000517:prevention & control; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D020011:Protective Agents / Q000378:metabolism*; D011897:Random Allocation; D012643:Selenium / Q000008:administration & dosage* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D012643:Selenium