Intense exercise is thought to increase oxidative stress and damage muscle tissue. Taurine is present in high concentration in skeletal muscle and may play a role in cellular defenses against free radical-mediated damage. The aim of this study was to determine if manipulating muscle levels of taurine would alter markers of free radical damage after exercise-induced injury. Adult male Sprague-Dawley rats were supplemented via the drinking water with either 3% (w/v) taurine (n = 10) or the competitive taurine transport inhibitor, beta-alanine (n = 10), for one month. Controls (n = 20) drank tap water containing 0.02% taurine and all rats were placed on a taurine free diet. All the rats except one group of sedentary controls (n = 10) were subjected to 90 minutes of downhill treadmill running. Markers of cellular injury and free radical damage were determined along with tissue amino acid content. The 3% taurine treatment raised plasma levels about 2-fold and 3% beta-alanine reduced plasma taurine levels about 50%. Taurine supplementation (TS) significantly increased plasma glutamate levels in exercised rats. Exercise reduced plasma methionine levels and taurine prevented its decline. Taurine supplementation increased muscle taurine content significantly in all muscles except the soleus. beta-alanine decreased muscle taurine content about 50% in all the muscles examined. Lipid peroxidation (TBARS) was significantly increased by exercise in the extensor digitorium longus (EDL) and gastrocnemius (GAST) muscles. Both taurine and beta-alanine completely blocked the increase in TBARs in the EDL, but had no effect in the GAST. Muscle content of the cytosolic enzyme, lactate dehydrogenase (LDH) was significantly decreased by exercise in the GAST muscle and this effect was attenuated by both taurine and beta-alanine. Muscle myeloperoxidase (MPO) activity was significantly elevated in the gastrocnemius muscle, but diet had no effect. MPO activity was significantly increased by exercise in the liver and both taurine and beta-alanine blocked this effect. There was no effect of either exercise or the diets on MPO activity in the lung or spleen. Running performance as assessed by a subjective rating scale was improved by taurine supplementation and there was a significant loss in body weight in the beta-alanine-treated rats 24 hours after exercise. In summary, taurine supplementation or taurine depletion had measurable cytoprotective actions to attenuate exercise-induced injury.

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Leptin is a protein secreted by adipocytes that is important in regulating appetite and adiposity. Recent studies have suggested the presence of leptin receptors in the arcuate nucleus of the hypothalamus (ANH). Neonatal administration of monosodium glutamate (MSG) damages the ANH, resulting in obesity and neuroendocrine dysfunction. Neonatal administration of MSG was utilized to test the hypothesis that the anatomic site for many of leptin's actions is the ANH. Female control (n = 6) and MSG-treated rats (n = 7) were implanted for 14 days with osmotic minipumps containing phosphate-buffered saline or leptin (1 mg.kg-1.day-1). Leptin suppressed (P < 0.05) body weight gain in controls but did not suppress weight gain in MSG-treated rats. Leptin decreased (P < 0.05) fat depots in controls but had no effect in MSG-treated rats. Night feeding was suppressed (P < 0.05) in leptin-treated control rats. MSG-treated rats showed a suppression in food intake that was of a smaller magnitude and appeared later in the course of leptin treatment. These findings suggest that leptin mediates some physiological actions related to fat mobilization via receptors located in the ANH.

Abstract:Taurine has been suggested to have cytoprotective actions via a number of different mechanisms. The role of taurine in protecting DNA from oxidative damage has received only limited attention. The aim of the present studies was to test the hypothesis that taurine might act to attenuate oxidative damage to DNA caused by free radicals generated by iron-stimulated catecholamine oxidation in the presence of H2O2. Calf thymus DNA (100 µg/tube) was exposed to a reaction mixture containing: ferric chloride (60 µM), H2O2 (2.8 mM) and L-dopa (100 µM). Taurine and taurine analogs were added simultaneously to determine their effects to prevent oxidative damage to DNA. The reaction was carried out for 1 hour at 37º C and terminated by rapid freezing in an ethanol/dry ice bath. The DNA was precipitated with ethanol and subsequently hydrolyzed with formic acid under vacuum. The hydroxylated bases were separated by HPLC and detected electrochemically. All experiments were replicated a minimum of 5 times. Taurine (20 mM) was found to reduce (p<0.05) damage to DNA as indexed by reductions in the formation of 5-OH-uracil 8-OH adenine and 8-OH guanine Taurine had minimal effects to reduce the formation of 5-OH cytosine Taurine (20 mM) also increased total DNA recovery after damage 3640% and increased total undamaged guanine -32%. 5-OH Uracil formation could be reduced (p<0.05) by 1 mM taurine and 8-OH-adenine formation was reduced (p<0.05) by 5 mM taurine. Studies were conducted with various amino acid analogs and total base adduct formation was reduced by 20 mM ß-alanine lysine and glutathione When tested at 20 mM, both hypotaurine and homotaurine provided greater protection against DNA damage than taurine, whereas isethionic acid provided a similar level of protection as taurine. Using identical conditions as the assays for base hydroxylation, we tested whether inhibition of quinone formation could account for taurine's mechanism of action. Taurine homotaurine and hypotaurine all reduced quinone formation. Thus, inhibition of quinone formation could account for part of taurine's mechanism of action to inhibit oxidative damage, but it could not account for homotaurine's greater efficacy in preventing DNA damage. Overall, these studies show that taurine at concentrations normally found in cells can inhibit oxidative damage to DNA.

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The nonobese diabetic (NOD) mouse is subject to autoimmune disease-associated lymphocytic attack on the salivary glands with a corresponding loss of exocrine function. Downregulation of stimulus response to the beta-adrenoceptor agonist, isoproterenol, appears to be related to a decline in beta-adrenergic receptor density, changes in the level of intracellular second messenger signaling component adenosine 3',5'-cyclic monophosphate, and protein kinase A activity. An autoantibody to the beta 1-adrenergic receptor present in the sera of diabetic NOD mice may be involved in the reduced agonist response by virtue of its ability to retard dihydroalprenolol radioligand binding to receptors in the membranes of salivary glands from control mice and recognition of purified beta 1-adrenergic receptor by immunoblotting techniques.

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