In utero hepatocellular transplantation in rats.

This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17) with fetal hepatocytes isolated from rats at the end of pregnancy (ED21). We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10) as well. Cellular viability reached the rates of 90-95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

Effect of ß-N-methylamino-L-alanine on oxidative stress of liver and kidney in rat.

ß-N-methylamino-(L)-alanine (L)-BMAA) is a neurotoxic amino acid, found in the majority of cyanbacterial genera tested. Evidence for implication of (L)-BMAA in neurodegenerative disorders, like amyotrophic lateral sclerosis (ALS), relies on bioaccumulation and biomagnification from symbiotic cyanobacteria. The involvement of (L)-BMAA in oxidative stress was demonstrated in several studies in the central nervous system. In the present study, we investigated the effect of (L)-BMAA on the oxidative stress responses of liver and kidney in rats treated by intraperitoneal administration with this amino acid. Oxidative stress was demonstrated by the quantification of lipid peroxidation, the measurement of both catalase and glutathione peroxidase activities, as well as the quantification of glutathione (GSH) levels and the total antioxidant capacity. It was observed that (L)-BMAA caused a significant increase in the degree of lipid peroxidation and catalase activity in both organs. A significant increase in glutathione peroxidase activity was obtained only in liver, whereas glutathione levels were also increased in both organs. The total antioxidant capacity decreased in liver and increased in kidney. These results suggest that the oxidative stress was higher in liver than in kidney, and might be crucial for (L)-BMAA toxicological action.