Cerebrocellular swelling in the presence of uraemic guanidino compounds: ameliorative effects of taurine.
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 micromol/l)(+22%) and guanidine hydrochloride (G, 3 micromol/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 micromol/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 GABAA receptor antagonist bicuculline (100 micromol/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 GABAA receptors.
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Department of Medical and Social Care Education, University of Leicester, UK. rol1@le.ac.uk
D000818:Animals; D001929:Brain Edema / Q000517:prevention & control*; D019791:Guanidine / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015538:Nitrosation; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000494:pharmacology*
D018696:Neuroprotective Agents; D013654:Taurine; D019791:Guanidine