Cerebrocellular Swelling in the Presence of Uraemic Guanidino Compounds: Ameliorative Effects of Taurine

Abstract

Cell volumes (equilibrium non-inulin spaces) have been measured in slices of rat cerebral cortex incubated in the presence of uraemic guanidino compounds. Of 5 guanidino compounds tested, all but one caused significant cell swelling. This was most pronounced for guanidinosuccinic acid (GSA, 40 μmol/l)(+22%) and guanidine hydrochloride (G, 3 μmol/l)(+13%). Swelling was reduced by taurine in a dose-dependent manner, being completely abolished at 20 mmol/l. Swelling was also abolished by the antioxidants ascorbic acid (0.4 mmol/l) and butylated hydroxytoluene (0.5 mmol/l), the free radical scavenger N-acetyl-l-cysteine (10 mmol/l) and the lipid peroxidase inhibitor desmethyl tirilazad (100 μmol/l). The remission of swelling by 20 mmol/l taurine was reduced by 50% by the taurine transport inhibitor guanidinoethylsulphonate (GES, 1 mmol/l). This figure was not significantly altered when the concentration of GES was increased to 10 mmol/l. It was also reduced by 45% by the GABA _a receptor antagonist bicuculline (100 μmol/l). It was completely abolished when both GES and bicuculline were present. It is suggested that guanidino compounds result in cells undergoing oxidative-nitrosative stress, and that taurine protects against the resultant cell swelling by 2 mechanisms One (intracellular) requires taurine transport and depends on its role as an antioxidant, with lipid peroxidation being probably a significant factor. The other (extracellular) is associated with activation of GABA _a receptors.