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Effects of taurine and hypotaurine on oxidative lung injury
Garland, Carroll Moses
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The present studies are based on the premise that pulmonary injury, during periods of hypoxia, ischemia, and reperfusion, may be due to increased production of reactive oxygen species, including the superoxide anion (02--), hydroxyl radical (-OH), and hydrogen peroxide (H202), and on the premise that this injury can be ameliorated by antioxidant pre-treatment. The sulfur-containing (Î²-amino acids, taurine and its precursor, hypotaurine, have been shown indirectly to possess antioxidant properties by several investigators. The mechanism(s) by which taurine and hypolaurine exert their antioxidant effects has(have) remained unclear despite many years of intensive study, as does the precise physiological role for these two Î²-amino acids. The goals of the present study were: 1) to evaluate the effects of taurine and hypolaurine in experiments that model biochemical events which are believed to be important components of oxidative pulmonary injury; 2) to assess the potential antioxiodant ability of the amino acids by determining their capacity to scavenge the free radicals, -OH and O2-., directly; and 3) to investigate the effect of these amino acids on reperfusion injury of rat lungs in an ex vivo ischemia-reperfusion injury model. The results of this study indicate that taurine and hypotaurine are not effective in detoxifying H202 and, in fact, taurine was found to augment H202 production in phorbol myristate acetate-stimulated macrophages. At 26, 78, and 104 mM, taurine was found to elevate H202 production 13%, 28%, and 43%, respectively, above the positive control. Taurine (5-120 mM) and hypotaurine (2-10 mM) were also ineffective (p > 0.05) in protecting biomembranes against free radical-induced lipid peroxidation. However, taurine (10-300 mM) and hypotaurine (2-30 mM) were found to possess the ability to scavenge hydroxyl radicals. Taurine (148 and 193 mM) and hypotaurine (19 mM) were found to possess the ability to scavenge superoxide at the high end of the concentration range tested. This was demonstrated by the ability of these amino acids to compete with both ferricytochrome c for available O2-- and deoxyribose for available -OH, within the rdespective systems designed to produce these two reactive species. Additionally, in an EPR study using 5,5-dimethyl-l-pyrroline-Noxide (DMPO) as a spin trap, both taurine and hypotaurine caused dose-dependent inhibition of DMPO-OH and DMPO-OOH adduct formation. In the ex vivo rat lung model, the addition of 5 and 10 mM taurine to the perfusion medium 20 minutes prior to the induction of ischemia appeared not to provide significant protection (p > 0.05) against reperfusion injury to isolated rat lungs exposed to 60 minutes of ischemia followed by 30 minutes of reperfusion. However, the data obtained from the ex vivo lung experiments was variable and must be interpreted with caution. Furthermore, in preliminary studies it was found that 50 mM taurine may be toxic to the isolated, perfused, rat lung. In conclusion, the antioxidant properties of taurine and hypotaurine are due to their capability to scavenge some of the reactive species of oxygen. The apparent inability of low concentrations of taurine to ameliorate post-ischemic reperfusion injury of lungs is consistent with the fact that relatively high concentrations of taurine were needed for the amino acid to demonstrate significant scavenging of O2-- and -OH.
- Masters Theses