| Autor: |
Baldassarre, M., Naldi, M., Zaccherini, G., Pompili, E., Tedesco, D., Nugnes, M., Fabini, E., Pock, K., Tedesco, G., Hegener, O., Bartolini, M., Caraceni, P. |
| Zdroj: |
Digestive & Liver Disease; 2024 Supplement 3, Vol. 56, pS319-S320, 2p |
| Abstrakt: |
The administration of human albumin (HA) is widely used in patients with decompensated cirrhosis to treat or prevent complications of the disease. HA is given to these patients because of its ability to effectively counteract hypovolemia by acting as a plasma expander. However, several lines of evidence suggest that the non-oncotic properties of the molecule may mediate the beneficial effects. Nevertheless, the HA molecules contained in standard commercial HA solution exhibit a number of oxidative and non-oxidative modifications that may dampen the therapeutic potential of commercial HA formulations. Unfortunately, definitive data on the cause and pattern of HA structural damage in commercial solutions are still lacking, so this study identifies critical steps in the manufacturing process as well as in the shelf life for the onset of structural damage in current commercial solutions. Albumin molecular structure was investigated by using high-performance liquid chromatography/electrospray ionization/mass spectrometry throughout the manufacturing process and at different lengths of shelf-life in standard commercial vials. The LC-MS analysis of samples collected at different steps of the fractionation process indicate that this procedure does not significantly affect albumin quality as the relative amount of reversibly and irreversibly oxidized albumin forms as well as the amount of albumin in its native form at the beginning of the post-production storage period resembles that of healthy donors. Contrary to the manufacturing process, shelf-life at room temperature was found to significantly impair the structural integrity of albumin already after 1 year, with a significant increase of the oxidized (HNA1: +10%; HNA2: 20%) and truncated (N-terminal: +29%) isoforms and a concomitant decrease of the reduced (HMA: -30%) and native (-40%) isoforms. Such results were confirmed by a prospective study in which several strategies to prevent the loss of native albumin in commercial formulation were also tested. This study unveiled that structural damages to the albumin molecule found in commercial formulation do not result from the manufacturing process, but they accumulate during shelf-life at room temperature. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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