RESUMEN
Oxalic acid is an end product of metabolism, and no significant degradation of oxalate occurs in mammals. The sole route of oxalate excretion is believed to be via the kidney. The extrarenal clearance of oxalate in control rats (N = 16) and in 5/6 nephrectomized rats (N = 25) with renal insufficiency was investigated. [14C]oxalic acid, approximately 2 microCi/day, was infused sc by a mini osmotic pump over 4 days. Excretion of 14C was measured in urine, in feces, and in expired CO2. The 14C content of kidney, heart, liver, muscle and bone was also determined at the time the animals were killed. Plasma oxalate was determined by an enzymatic method and by an isotopic dilution procedure. Creatinine clearance in the controls was 1.82 +/- 0.1 mL/min (mean +/- SE) compared with 0.31 +/- 0.04 mL/min (P < 0.0005) in the nephrectomized rats. Plasma oxalate was 5.6 +/- 0.6 mumol/L in controls and 27.0 +/- 3.9 (mean +/- SE; N = 24) in nephrectomized animals (P < 0.0005). The total 14C recovered in urine, feces, and CO2 combined was similar in both groups. The 14C excreted in the feces over the 4-day period was 27.8 +/- 1.5% (of the 14C recovered) in rats with renal failure and 6.5 +/- 0.5% in controls (P < 0.0005). Percent fecal 14C excretion in nephrectomized rats was inversely correlated with creatinine clearance (r = 0.80; P < 0.0001) and directly correlated with plasma oxalate (r = 0.66; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Mucosa Intestinal/metabolismo , Fallo Renal Crónico/metabolismo , Oxalatos/metabolismo , Animales , Transporte Biológico , Huesos/química , Heces/química , Fallo Renal Crónico/etiología , Masculino , Músculos/química , Nefrectomía/efectos adversos , Oxalatos/farmacocinética , Ácido Oxálico , Ratas , Ratas Wistar , Distribución Tisular , Orina/química , Vísceras/químicaRESUMEN
We measured phospholipase A2 (PLA2; EC 3.1.1.4) activity in normal and uremic plasma, using [1-14C]oleate-labeled autoclaved Escherichia coli as substrate. Hydrolysis of bacterial phospholipid by crude plasma from both groups was optimal at pH 5.5, was specific for the 2-acyl position of phospholipids, and had an absolute requirement for calcium. Activity was greatest in the presence of added Ca2+, 5 mmol/L, but this increase was inhibited by several divalent cations (Mg2+, Zn2+, Cu2+, Ba2+, Co2+, Pb2+, Fe2+) and by Fe3+. PLA2 activity was also inhibited by heparin at acid and alkaline pH, normal plasma being more sensitive than uremic plasma to this inhibition. Enzyme activity in undiluted plasma was eightfold greater in uremic than in normal plasma. Dilution of plasma by two to fourfold increased the total activity of both normal and uremic plasma. However, the relative differences in total activity between the groups remained constant (eight- to 11-fold). The cause and consequences of the increased PLA2 activity in uremia remain to be established.