Effects of taurine and chemically-related sulfur-containing compounds on oxidant- and nonoxidant-induced red blood cell membrane damage and antioxidant status.

摘要

This study has evaluated the actions of taurine (TAU), twelve sulfur-containing structurally related to TAU (N-(2-acetamido)-2-aminoethanesufonic acid, aminomethane-suffonic acid, N-acetylcysteine, L-cysteic acid, α-sufo-β-alanine, ethane-sulfonic acid, 1,2-ethanedisulfonic acid, homotaurine, hypotaurine, isethionic acid, 3mercaptoeth-anesufonic acid, N-methyltaurine) and cromolyn sodium (CROM) on oxidant and nonoxidant-induced cell damage. Using hydrogen peroxide (H ₂O₂), phenylhydrazine (PHZ) and tert-butyl hydroperoxide (bhp) as model oxidants, and intact rat erythrocytes (RBCs) as a test system, indices of membrane damage (i.e., hemoglobin, lactate dehydrogenase, potassium ions) and of antioxidative status (i.e., reduced glutathione, methemoglobin, catalase, glutathione peroxidase, superoxide dismutase) were measured. TAU (25–175 mM) protected RBCs against oxidant-induced cell damage and impairment of the antioxidative defenses in a manner and to an extent that were dependent on both its concentration and that of the oxidant (H₂O₂: 5–40 mM; PHZ: 75–100, tBHP: 0.5–3 mM). By treating rats with TAU (2.4 mM/kg, divided doses, ip) before a single dose of PHZ (75 mg/kg, ip), it was verified that TAU was also able to protect RBCs under in vivo conditions. Through the use of cholic acid (CHOLAC), saponin (SAP) and hypoosmotic (0.4%) NaCl as nonoxidant hemolyzing agents, it was shown that TAU protected RBCs only against CHOLAC- and 0.4% NaCl-related cellular damage. From the results of in vitro and in vivo experiments with compounds representing analogs and homologs of TAU, it was determined that the protective actions of this amino acid against oxidant- and nonoxidant-induced RBC alterations are centered on its sufonate group. Structural alterations of the TAU molecule such as chain length, N-substitution, α- or β-carboxylation, reduction of the sufonate to a sulfinate group, deamination and replacement of the amino group by another functionality exerted variable effects on the protection by TAU. N-Methylation and replacement of a sulfhydryl group for the β-amino group, on the other hand, abolished the protective properties of TAU. Moreover, protection by TAU and its congeners appeared to take place extracellularly and through weak, noncovalent interactions, since the protection disappeared upon washing RBCs that had been pretreated with a sulfur-containing compound with buffer solution, and since it remained unaltered in the presence of β-alanine, an inhibitor of TAU uptake into cells. In contrast, protection by CROM, a known membrane stabilizer, was unaffected by the washing step.