[Influence of hyaluronan on peritoneal permeability for macromolecules in vitro].
Recent studies pointed out advantages of high-molecular hyaluronic acid (HA) application into dialysis fluids. This molecule is an essential component of peritoneal extracellular matrix. The compound shows antiadhesive properties and participates in restoring of peritoneal integrality and remodeling of peritoneum, which have been changed by prolonged peritoneal dialysis and returning incidents of peritonitis. Influence of HA on transperitoneal transport of large and small molecules is recognized in a little range. The aim of presented studies in vitro was qualification of hyaluronan influence on transport dynamics of the selected macromolecules (albumin 1 g/dL, icodextrin 7.5 g/dL and insulin 0.1 g/dL). Values of the transfer, directed from the interstitial to the mesothelial side of membrane (I-->M) and in the opposite direction (M-->I) were expressed as coefficient of diffusive permeability P [cm/s]. In the case of each macromolecule, two separate research series of the experiments were done. In the first one transperitoneal transport in the control conditions (120 min) was analyzed, and in the secondtransfer parameters before (15-60 min) and after hyaluronan (0.04 g/dL) application on the mesothelial side of peritoneal membrane (75-120 min) were examined. Stability of albumin and insulin transport (in the case of the both transfer directions) and icodextin passage (only M-->I direction) was observed in the presented studies when we compare the first and the second hours of the experiments. In the opposite direction (I-->M) it was showed an increase of its transport with time by about 50%. The mean values of P +/- SEM amounted to 0,271 +/- 0,056 [x10(-4); cm/s] and 0,315 +/- 0,057 [x10(-4); cm/s] for albumin and 0,145 +/- 0,033 [x10(-4); cm/s] and 0,146 +/- 0,022 [x10(-4); cm/s] for insulin, respectively in the case of I-->M and M-->I directions and 0,194 +/- 0,035 [x10(-4); cm/s] for icodextrin transfer directed from the mesothelial to the interstitial side of membrane. In the opposite direction (I-->M) values of P coefficient amounted to: 0,280 +/- 0,038 [x10(-4); cm/s] in the first experimental hour, and 0,394 +/- 0,046 [x10(-4); cm/s] in the second one. It was observed also asymmetry of glucose polymer passage with I-->M transfer domination. Hyaluronan eliminated this asymmetry. After use this compound the transport parameters of icodextrin were stable for the both I-->M and M-->I directions. Hyaluronan did not change values of diffusive permeability coefficients P in the case of bidirectional transfer of albumin and insulin. The obtained results show, that values of macromolecules transfer across peritoneum in vitro don't depend on their molecular weight and isoelectric points. Dynamics of albumin and insulin transperitoneal passage is stable. Icodextrin transport, directed from the interstitial to the mesothelial side of membrane, predominates transfer in the opposite direction. Hyaluronan modifies dynamics of transperitoneal icodextrin passage, but doesn't influence on permeability of the membrane in the case of albumin and insulin.
Grzelak
Teresa
T
Katedra Chemii i Biochemii Klinicznej AM im. Karola Marcinkowskiego w Poznaniu. tgrzelak@amp.edu.pl
Czyzewska
Krystyna
K
Szary
Beata
B
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D005936:Glucans / Q000493:pharmacokinetics; D005947:Glucose / Q000493:pharmacokinetics; D015312:Hemodialysis Solutions / Q000493:pharmacokinetics*; D006820:Hyaluronic Acid / Q000494:pharmacology*; D000077607:Icodextrin; D066298:In Vitro Techniques; D007328:Insulin / Q000493:pharmacokinetics; D046911:Macromolecular Substances / Q000493:pharmacokinetics*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D011817:Rabbits
D000418:Albumins; D005936:Glucans; D015312:Hemodialysis Solutions; D007328:Insulin; D046911:Macromolecular Substances; D000077607:Icodextrin; D006820:Hyaluronic Acid; D005947:Glucose