Comparación de dos métodos de medida de la depuración plasmática del complejo a2-macroglobulina-monofluorofosfato (a2m-mfp) en la rata.

AGUIRRE CRISTINA; ARMENDARIZ MIRTA; MENOYO INÉS; RIGALLI ALFREDO; PUCHE RODOLFO

Rosario

Congreso; . VI Congreso y XXIV Reunión Científica anual de la Sociedad de Biología de Rosario; 2004

Socidedad de Biología de Rosario

PLASMATIC CLEARANCE OF a2-MACROGLOBULIN-MONOFLUOROPHOSPHATE (a2M-MFP) COMPLEX IN THE RAT. Comparison of two methods of measurement. Aguirre MC, Armendáriz MN,; Menoyo I, Rigalli A, Puche RC. Fc. Cs. Bioquímicas y Farmacéutica. Fac. de Ciencias Médicas. UNRosario. In the rat, a2M is an acute phase reaction globulin, which protects tissues from the action of proteinases. a2M plays an important role in MFP pharmacokinetic, forms a a2M-MFP complex and inactivates the antiproteasic activity. Based on these phenomena we developed two methods to calculate the plasmatic clearance of a2M-MFP (kc). Method A: with a mathematical model and the values of plasmatic a2M-MFP concentrations after a single intravenous (iv.) dose of MFP. Method B:  with plasmatic concentrations of a2M after an oral dose of MFP. This work compares the values of kc by both methods with that obtained by iv. injection of purified complex. Three types of experiments were carried out in adult IIM/Fcm rats. 1) iv. administration of a2M-MFP and measurement of its concentration for 75 min. Data followed a mono-exponential function with kc= 0.1231±0.0227 min-1. 2) iv. administration of a single dose of MFP, and measurement of a2M-MFP concentrations. Data were fitted with a mono-exponential function with kc= 0.1819±0.153 min-1. 3) iv. administration of an oral dose of MFP and determination of a2M concentrations by dot-blot. Data were adjusted with a mono-exponential function with kc= 0.0082±0.0042 min-1. Kc obtained in experiments 1 and 2 significantly differed from that obtained in experiment 3. ANOVA P<0,05. Conclusions: 1- The value of kc obtained with method A described the plasmatic clearance of a2M-MFP. 2- Method B underestimates the value of kc.