Chapter 6.4: Long Term Effects on the Histology and Function of Livers and Spleens in Rats after 33% Toploading of PEG-PLA Nano-Artificial Red Blood Cells
The text and figures from this paper come from Ref. 14 with copyright permission.
This study investigates the long-term effects of nano-dimension PEG-PLA artificial red blood cells (RBCs) containing hemoglobin and RBC enzymes on the liver and spleen after a one-third blood volume toploading in rats. The experimental rats received one of the following infusions: Nano-artificial RBCs in Ringer’s lactate solution, stroma-free hemoglobin, polyhemoglobin and autologous rat whole blood. Blood samples were taken before infusions and after infusions on Days 1, 7 and 21 for analysis. Nano-artificial RBCs, polyhemoglobin, Ringer’s lactate solution and rat RBCs did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand stroma-free hemoglobin induced significant adverse effects on the liver, as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On Day 21 after the infusions, rats were sacrificed and their livers and spleens were excised for histological examination. Nano-artificial RBCs, polyhemoglobin, Ringer’s lactate solution and rat RBCs did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in the rats’ central veins and sinusoids and hepatic steatosis. In conclusion, injected nano-artificial RBCs can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on livers or spleens.
