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This study investigates the long-term effects of PEG-PLA nano-artificial cells containing hemoglobin (nanoRBCs) on renal function and renal histology after a one-third blood volume toploading in rats. The experimental rats received one of the following infusions: NanoRBCs in Ringer’s lactate solution, stroma-free hemoglobin (SFHb), polyhemoglobin (polyHb) or autologous rat whole blood (rat RBCs). Blood samples were taken before infusions and on Days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on Day 21 after the infusions and their kidneys were excised for histology examination. Infusion of SFHb induced significant decrease in renal function damage as evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in the SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed to be damaged. There was no abnormalities in renal biochemistry or histology in all the other groups (nanoRBCs, polyHb, Ringer’s lactate solution and rat RBCs). In conclusion, the injections of nanoRBCs did not have adverse effects on renal function or remal histology.
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.