Background

Fructose-induced hypertension was used to test the hypothesis thattaurine supplementation and/or exercise can prevent hypertensionand increase exercise capacity.

Methods

Five groups of 15 Sprague–Dawley rats were allocated and designated as control, high fructose–fed (fructose), high fructose–fed plus exercise (FE), high fructose–fed plus 2% taurine supplement(FT) and high fructose–fed plus 2% taurine supplement and exercise(FET) groups. Noninvasive systolic blood pressure (SBP) was recordedweekly and invasive arterial blood pressure (ABP) was recorded atthe end of the 4-week trial. Three consecutive swimming tests wereperformed in the selected rats from each group and the plasmabiomarkers were measured in the remaining rats.

Results

Noninvasive SBP differed significantly (P < 0.001) from week 3, bothnoninvasive and invasive ABP increased significantly (P < 0.001),and exercise capacity significantly decreased (P < 0.001) in thefructose group compared with the control group. The individual effects of swimming and taurine supplementation were incapable of preventing the development of hypertension and SBP significantly(P < 0.001) increased in the FE and FT groups; exercise capacity in those groups remained similar to control. The combined effects of exercise and taurine all eviated hypertension and significantly increased exercise capacity in the FET group. Insulin resistance increased significantly and plasma nitric oxide (NO) decreased significantly in the F, FE, and FT groups. Both parameters remained similar to control values in the FET group with an increasing antioxidant activity.

Conclusion

Taurine supplementation in combination with exercise prevents hypertension and increases exercise capacity by possibly antioxidation and maintaining NO concentrations.

American Journal of Hypertension, advance online publication 3 February 2011; doi:10.1038/ajh.2011.4

A high fructose–fed rat model of insulin-resistance syndrome has a metabolic profile very similar to that of the human X syndrome, which is associated with a high incidence of cardiovascular disease and hypertension.1 Insulin resistance, hyperglycemia, increased vascular resistance, sodium retention, and sympathetic overactivity have been linked to the development of hypertension.2,4 Taurine (2-aminoethanesulphonic acid) is the most abundant, nonessential, sulfur-containing amino acid found at high concentrations in skeletal muscle, heart, blood, nerve, brain, liver, and other organs. Many biological, physiological, and pharmacological functions of taurine have been reported in various tissues and species, including detoxification, osmoregulation, antioxidation, membrane stabilization, modulation of ion flux,5 and cardiovascular functions such as the regulation of hypertension.6 A previous study showed that taurine decreases the activation of mitogen-activated protein kinase and Bax, which prevents the generation of reactive oxygen species induced by lipopolysaccharides.7 Another study showed that taurine protects against DNA damage by oxidative injury by inhibiting quinone formation.8 Oral taurine supplementation decreases blood pressure without significant side effects as previously reported elsewhere.9 Exercise is frequently recommended as a useful way to lower blood pressure for the management of hypertension.10,11 Hypertension decreases exercise performance12 and augments the aging process; therefore, athletes and other physically active patients should be screened for high blood pressure, and appropriate supplementation with antihypertensive agents is recommended for correction. To explore the potential of taurine as such a supplement, the present study used a high fructose–fed rat model to investigate the influence of oral taurine supplementation on insulin resistance, development of hypertension, and decreased exercise capacity.

Methods

Animal preparation. Male Sprague–Dawley rats (6 weeks of age and 120–140g in weight) were purchased from the Korean Research Institute of Bioscience and Biotechnology (Daejeon, Korea). The rats were housed in a room with a temperature of 23 ± 5°C and alternating 12-h dark-light cycles. The animals were fed standard rat chow (20% crude protein, 4.5% crude fat, 6.0% crude fiber, 7% crude ash, 0.5% calcium, and 1% phosphorus) and were allowed free access to tap water during the adaptation period.

Experimental protocol. The rats were randomly allocated to five groups, each containing 15 rats. One group served as control. The remaining four groups were fed 35% fructose (Sigma-Aldrich St Louis, MO) in the chow and 5% fructose in drinking water,13,14 which collectively established an average 43.6 ± 0.1% fructose of the total food consumed. The daily intakes of the rats are presented in Table 1. The four high fructose–fed groups were designated as follows: high fructose–fed sedentary (fructose), high fructose–fed plus exercise (FE), high fructose–fed plus taurine supplementation (FT), and high fructose–fed plus exercise and taurine supplementation (FET). The FT and FET groups received 2% taurine dissolved in the drinking water. After 2 weeks, five representative rats from each group were selected and tagged for swimming capacity and fatigue tests. The investigation conformed to the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85–23, revised 1996).

Table 1

Body weight, food intake, fluid intake, fructose consumption, and taurine consumption during 4 weeks experiment period

Swimming. An adjustable current swimming pool (100cm in length, 60cm in width, and 70cm in height, and 35-cm water depth) was used for the swimming test. The current in the pool was generated by four horizontally seated type BT-30F water pumps (Chuangxing Electrical, Chuangxing, China). The FE and FET groups were subjected to 1h of swimming daily between 9:00 and 11:00AM 6 days per week, with 1 day off per week for rest. The strength of the current was adjusted by changing the water flow, and each pump was adjusted to a flow rate of 5.2 ± 0.6l/min for swimming.

Swimming capacity and fatigue tests. After 4 weeks of regular exercise sessions, five rats from each group were selected for the swimming capacity test. The control and fructose groups had been trained every second day, 10min per session, in the last 2 weeks before completion. Three fatigue tests were performed every other day as previously described.13

Blood pressure measurement. SBP was measured noninvasively each week with a Rat Tail NIBP System manometer-tachometer (ADI Instruments, Heidelberg, Germany) using a B60-7/16″ size tail-cuff (IITC Life Science, Woodland Hills, CA.) during the experimental period. Invasive arterial blood pressure (ABP) was measured at the end of the trial in rats anesthetized with ethyl carbamate (1.8g/kg body weight, intraperitoneally). A catheter with an outer dimension of 0.96mm and an inner dimension of 0.58mm (Fisher Scientific, Pittsburgh, PA) was inserted into the carotid artery, and the ABP was recorded with a computerized transducer system (MP150; Biopack, Santa Barbara, CA) using Acknowledge 3.5 software (East Palo Alto, CA).

Measurement of blood electrolytes and plasma glucose, and insulin. Blood electrolytes were measured immediately in a fresh blood sample (300µl) with the use of a Nova stat profile M ion selective electrode (Nova Biomedical, Waltham, MA). Plasma glucose was measured with a Spotchem SP-4410 auto-dry blood chemistry analyzer (Polymedco, Cortland Manor, NY) using a glucose measuring strip (Arkray, Kyoto, Japan). Plasma insulin was measured with a radioimmunoassay method (IVD Technologies, Santa Ana, CA) according to the manufacturer's protocol.

Antioxidant component system measurement. Plasma malondialdehyde (MDA) concentrations were measured with an MDA assay kit (Biomol International, Plymouth Meeting, PA) at an absorbance of 586nm according to the manufacturer's protocol. Thiol concentrations were measured based on the reactivity of thiol groups with Ellman reagent (5,5′-dithiobis[2-nitrobenzoic acid]), which led to a colorimetric reaction modified as described previously.15 Reduced glutathione (GSH) and blood GSH16 concentrations were measured as previously described. Oxidized glutathione (GSSG) was measured using the previously described method.17 The samples were deproteinized with 20% trichloroacetic acid. For GSSG measurement, 50-µl acidic supernatant aliquots were treated with 2µl 2-vinylpyridine and mixed continuously for 60min for masking of GSH (2µl added to 50µl supernatant). During the preincubation period, the pH was adjusted to about 6 with triethylamine.18 Each sample was analyzed in duplicate, and the average value was used. The redox ratio (GSH/GSSG) was calculated by using the formula GSH/GSSG = (GSHt − 2GSSG)/GSSG, as described previously.19

Plasma nitrite/nitrate measurement. Nitrite/nitrate, the major metabolite of nitric oxide (NO), was measured in plasma using a Nitrite/Nitrate Colorimetric Assay Kit (Fluka Analytical, Seelze, Germany). Nitrite accumulation in the plasma was determined by first reducing the nitrate using nitrate reductase. Nitrite was assayed colorimetrically after reaction with the Griess reagent (Sigma-Aldrich) according to the manufacturer's protocol. The absorbance was determined using a SpectraMax M2 microplate reader (Molecular Devices, Sunnyvale, CA) at 540nm. All measurements were performed in duplicate.

Data presentation and analysis of results. The data were analyzed by using Graph Pad Prism program version 5.02 (GraphPad Software, La Jolla, CA), and the data are expressed as mean ± s.e.m. Differences were compared between the groups by using a Bonferroni post hoc test followed by a nonrepeated one-way analysis of variance vs. the control or fructose group. In order to compare differences depending on time and treatment, a nonrepeated two-way analysis of variance was performed following a Bonferroni post hoc test for SBP data measured by tail cuff over 4 weeks. A P value <0.05 was considered to indicate a statistically significant difference.

Results

Electrolyte status in the blood

Results of electrolyte measurements and acid-base status (pH) in the blood are shown in Table 2. Sodium ion concentration was significantly greater (P < 0.001) in the fructose and FE groups than in the control group. Na+ in the FT and FET groups was not significantly different from that in the control and fructose groups. The concentration of Cl was significantly lower (P < 0.001) in the fructose, FT and FET groups compared with the control group and the difference was not significant between the FE group and the control and fructose groups. Hematocrit was significantly lower (P < 0.001) in the fructose group than in the control group and was significantly greater (P < 0.001) in the FE, FT, and FET groups than in the fructose group; hematocrit levels in the FT and FET groups were not significantly different from the level in the control group.

Table 2

Blood ionic status in different groups after the 4 weeks trial of taurine supplementation and exercise and their combined effect in high fructose–fed rats

Effect of taurine and exercise on noninvasive SBP and invasive systolic ABP

The initial and final noninvasive SBP values in the control group were 114.5 ± 0.9 and 116.3 ± 1.4mmHg, respectively. A gradually increasing SBP was recorded in the fructose, FE, and FT groups. The initial and final SBP values were 115.1 ± 1.5 and 129.2 ± 0.9mmHg, respectively, for the fructose group; 114.3 ± 1.2 and 125.4 ± 1.5mmHg, respectively, for the FE group; and 114.5 ± 1.4 and 122.8 ± 1.2mmHg, respectively, for the FT group (Figure 1). After 4 weeks, SBP increased significantly (P < 0.001) in the fructose group, considering both time and treatment. The SBP was 118.2 ± 1.1mmHg in the FET group after 4 weeks, with no significant difference considering both time and treatment.

Systolic blood pressure (BP) in conscious rats measured with the tail-cuff method during the 4-week trial. Data are presented as mean ± s.e.m (n = 10). **P < 0.01. ***P < 0.001, Bonferroni post hoc test following two-way ANOVA vs. the control group. ††P < 0.01. †††P < 0.001, Bonferroni post hoc test following two-way ANOVA vs. the fructose group and ##P < 0.01. ###P < 0.001. While FET vs. FE. n = 10 per group. F, fructose, high fructose–fed group; FE, high fructose–fed plus exercise group; FET, high fructose–fed plus exercise and taurine supplement group; FT, high fructose–fed plus taurine supplement group.

The invasive systolic ABP values in the control, fructose, FE, FT, and FET groups were 115.4 ± 1.6, 134.2 ± 2.8, 122.6 ± 2, 123.1 ± 1.7, and 115.2 ± 1.3mmHg, respectively, at the end of the 4-week trial (Figure 2a). Systolic ABP increased significantly in the fructose (P < 0.001) and FT (P < 0.05) groups, but the difference was not significant between the FE and FET groups and the control group. However, ABP was significantly lower (P < 0.001) in the FE, FT, and FET groups than in the fructose group. Diastolic ABP values in the control, fructose, FE, FT, and FET groups were 78.7 ± 2.6, 103.4 ± 3.9, 81.5 ± 3.6, 91.4 ± 1.4, and 75.1 ± 3.1mmHg, respectively. Diastolic ABP was significantly greater (P < 0.001) in the fructose group than in the control group and was significantly lower (P < 0.001) in the FE, FT, and FET groups than in the fructose group. Mean ABP values were 90.8 ± 2.2, 113.7 ± 3.4, 95 ± 2.9, 101.9 ± 1.2, and 88.5 ± 2.3mmHg in the control, fructose, FE, FT, and FET groups, respectively. Mean ABP was significantly greater (P < 0.001) in the fructose group than in the control group and was significantly lower (P < 0.001) in the FE, FT, and FET groups than in the fructose group.

Carotid arterial blood pressure (BP) (systolic, diastolic, and mean) in (a) anesthetized rats and (b) results of the swimming capacity test at 4 weeks. The control and fructose groups had a short training period each day during the final week before the final competition events. Data are presented as mean ± s.e.m. *P < 0.05. ***P < 0.001, Bonferroni post hoc test following one-way ANOVA vs. the control group. P < 0.05. †††P < 0.001, Bonferroni post hoc test following one-way ANOVA vs. the fructose group (a, n = 10; b, n = 5). Con, control group; F, fructose, high fructose–fed group; FE, high fructose–fed plus exercise group; FET, high fructose–fed plus exercise and taurine supplement group; FT, high fructose–fed plus taurine supplement group.

Swimming capacity

Average swimming time in the control group of animals was 65.9 ± 2.9min, which was significantly greater (P < 0.001) than that (38.4 ± 1.5min) in the fructose group (Figure 2b). The swimming time in the FE group was 59.3 ± 1.2min, which was not significantly different from that in the control group but was significantly different (P < 0.001) from that in the fructose group. An extended swimming time of 71.7 ± 2.8min was recorded in the FT group, but the difference was not significantly different from the control group. The maximum swimming time of 80.3 ± 1.1min was recorded in the FET group, which differed significantly (P < 0.001) from the control and fructose groups.

Plasma glucose and insulin and insulin resistance

Plasma glucose concentrations in the control, fructose, FE, FT, and FET groups were 194 ± 10, 450 ± 4, 318 ± 33, 354 ± 16, and 189 ± 9mg/dl, respectively (Figure 3a). Plasma glucose was significantly greater (P < 0.001) in the fructose, FE, and FT groups than in the control group, but the comparative difference in the FET group was not significant. Plasma insulin in the fructose group (32.3 ± 1.1mU/l) was significantly greater (P < 0.001) than that in the control group (18.2 ± 1.2mU/l). Insulin concentrations in the FE, FT, and FET groups were 27.1 ± 1.1, 23.9 ± 1.5, and 21.1 ± 1.4mU/l, respectively, and concentrations in the FE and FT groups were significantly different from the concentration in the control group (P < 0.001 and P < 0.05, respectively; Figure 3b).

Effects of the swimming test and taurine supplementation individually and in combination on (a) glucose concentrations, (b) insulin concentrations, and (c) insulin resistance in the plasma of high fructose–fed rats after the 4-week trial. The control and fructose groups had a short training period each day during the final week before the final competition events. Data are presented as mean ± s.e.m. ***P < 0.001, Bonferroni post hoc test following one-way ANOVA vs. the control group. †††P < 0.001, Bonferroni post hoc test following one-way ANOVA vs. the fructose group. n = 10 per group. Con, control group; conc., concentration; F, fructose, high fructose–fed group; FE, high fructose–fed plus exercise group; FET, high fructose–fed plus exercise and taurine supplement group; FT, high fructose–fed plus taurine supplement group.

Insulin resistance was calculated as (glucose (mmol/l) × insulin (mU/l))/22.5. The greatest insulin resistance was calculated in the fructose group (35.9 ± 1.3), which differed significantly (P < 0.001) from that in the control group (8.7 ± 0.6). Insulin resistance was significantly greater (P < 0.001) in the FE and FT groups (21.2 ± 2.3 and 20.9 ± 1.8, respectively) than in the control group. Insulin resistance in the FET group (9.8 ± 0.7) was not significantly different from that in the control group (Figure 3c).

Creatine kinase in plasma

Plasma creatine kinase (CK) concentrations in the control, fructose, FE, FT, and FET groups were 446 ± 11, 811 ± 94, 1,414 ± 156, 519 ± 48, and 423 ± 97IU/l, respectively (Figure 4). CK was significantly greater in the fructose group (P < 0.05) and the FE group (P < 0.001) than in the control group but remained similar to the baseline level in the FET group.

Effects of the swimming test and taurine supplementation individually and in combination on the plasma concentration of creatine kinase (CK) in the different groups at the end of the trial. The control and fructose groups had a short training period each day during the final week before the final competition events. Data are presented as mean ± s.e.m. *P <0.05. ***P <0.001, Bonferroni post hoc test following one-way ANOVA vs. the control group. †††P <0.001, Bonferroni post hoc test following one-way ANOVA vs. the fructose group. n = 10 per group. Con, control group; F, fructose, high fructose–fed group; FE, high fructose–fed plus exercise group; FET, high fructose–fed plus exercise and taurine supplement group; FT, high fructose–fed plus taurine supplement group.

Antioxidant component system

High fructose feeding significantly (P < 0.001) increased plasma MDA levels and decreased the concentration of plasma thiols in the fructose, FE, and FT groups. Both exercise and taurine supplementation were effective at improving the levels of MDA and thiols. The differences between the FET and control groups were not significant, but a significant decrease was found between the FET and fructose groups. Taurine supplementation along with exercise maintained plasma MDA and thiols near the control value (Table 3). High fructose consumption in the fructose group significantly (P < 0.001) decreased the blood level of GSH in the fructose and FE groups, but the values were not significantly different from the control group. A significant (P < 0.001) increase in GSSG was observed in the fructose group, but GSSG in the FE, FT, and FET groups was not significantly different from that in the control group. The GSH level was significantly (P < 0.001) restored in the FT and FET groups by taurine supplementation and by the combined effect of taurine supplementation and exercise (Table 3). Both exercise (P < 0.001) and taurine supplementation (P < 0.001) were significantly effective at decreasing the GSSG concentration. The combined effect of exercise and taurine supplementation successfully maintained the GSSG level in the FET group. The GSSG level was not significantly different between the FET and control groups, but was significantly (P < 0.001) different between the FET and fructose groups (Table 3). The redox ratio (GSH/GSSG) was significantly (P < 0.001) lower in the fructose group, by about half, than in the control group. GSH/GSSG in the FE and FT groups improved with the individual effect of exercise and taurine supplementation. GSH/GSSG in the FET group was maintained near the control value by the combined effect of exercise and taurine supplementation (Table 3).

Table 3

Antioxidant component system after the 4 weeks trial of taurine supplementation and exercise and their combined effect in high fructose fed rats

Plasma nitrite/nitrate

The mean plasma concentration of nitrite/nitrate was 22.1 ± 1.5µmol/l in the control group and, in comparison, was significantly lower (P < 0.001) in the fructose, FE, and FT groups: 9.8 ± 1.1µmol/l (55.6%), 12.9 ± 0.9µmol/l (41.5%), and 15.2 ± 1.1µmol/l (31.2%), respectively. The combined effect of exercise and taurine supplementation maintained the plasma nitrite/nitrate concentration at 18.8 ± 0.6µmol/l in the FET group, which was 14.9% less than that in the control group (Figure 5).

Effects of the swimming test and taurine supplementation individually and in combination on plasma concentrations of nitric oxide (NO) in the different groups at the end of the trial. The control and fructose groups had a short training period each day during the final week before the final competition events. Data are presented as mean ± s.e.m. ***P < 0.001, Bonferroni post hoc test following one-way ANOVA vs. the control group. P < 0.05. †††P < 0.001, Bonferroni post hoc test following one-way ANOVA vs. the fructose group, n = 10 per group. Con, control group; F, fructose, high fructose–fed group; FE, high fructose–fed plus exercise group; FET, high fructose–fed plus exercise and taurine supplement group; FT, high fructose–fed plus taurine supplement group.

Discussion

The results of the present study in a rat model of insulin resistance indicate that high dietary fructose may be linked to the development of hypertension and a consequent decrease in exercise capacity in a manner that is possibly related to oxidative stress. The observed changes in markers of free radical damage are consistent with exercise-induced muscle injury. High reactivity of fructose and its metabolite may contribute substantially to the glycation of proteins.20 Taurine, which contains a free amino group, may form a Schiff base with sugar carbonyls and, hence, spare proteins from glycation if they can be maintained at high concentrations in the tissues. Taurine is often classified as an antioxidant, and its physiological effects contribute to a reduction in oxidative stress and protect tissue damage through inhibition of reactive oxygen species formation.7 In the biosynthetic pathway for taurine, GSH, and hypotaurine and their associated enzyme systems are considered true antioxidative systems, similar to the superoxide dismutase enzyme system, for example. Taurine may prevent Ca2+ overload and thereby minimize free radical generation, with the protective effect reflected in the degree of lipid peroxidation and NO production.21

The currently used biomarkers of antioxidation, plasma chemistry measures (CK, glucose, insulin, and insulin resistance), NO status, and blood ions (Na+, K+, and Cl) might be useful in a clinical assessment of the benefits of exercise training and/or taurine supplementation programs for preventing hypertension and achieving better performance. A previous study reported that taurine has a cytoprotective role in exercise-induced muscle injury.22 Other studies showed that taurine increases force production in skeletal muscles with antifatigue properties.23,24 In agreement with these reports, the increased CK levels in this study might be an indicator of muscle and myocardial damage. High fructose feeding caused oxidative injury, which was further augmented by swimming, and taurine showed protective effects in this study.

Increased Na+ concentrations in the circulation promote hypertension-induced hypertrophy of the vascular wall.25 Oral taurine supplementation can modify Na+ homeostasis in high fructose–fed rats.26 Moreover, taurine has an insulin-like action on glucose metabolism that accelerates glucose uptake into the liver and muscle,27 and exercise additionally raises insulin activity, which reduces insulin resistance and improves glucose intolerance.

The increase in plasma MDA levels observed in the current study and the corresponding decrease in plasma thiols reflect the upregulation of protein oxidation with high fructose feeding. In most cases, taurine supplementation appeared to blunt the exercise-induced decrease in acid-soluble thiols. The available evidence suggests that physical exercise increases the activity of antioxidant enzymes and whereas acute exercise can induce oxidative stress in untrained individuals, regular exercise reduces oxidative stress.28,29 Exercise increases free radical production and attendant lipid peroxidation, with no effect of either isometric or dynamic exercise on plasma MDA levels.30 Hypoxic exposure increases plasma MDA levels in athletes, and increased oxidative damage provokes a marked reduction in physical performance.31,32 Exercise improves prognosis in hypertensive heart disease by increasing the efficiency of the antioxidant system and preserving mitochondrial energy metabolism.33 GSH is another fundamental defense mechanism during conditions of increased oxidative stress. Blood levels of GSH appear to decrease with acute exercise and are sometimes accompanied by an increase in GSSG.34 In addition to causing reactive oxygen species–mediated NO inactivation, oxidative stress can inhibit NO synthase activity.35 The observed elevation of NO in the plasma of exercised rats was probably due to changes in oxidative balance and/or to exercise-related increased endothelial shear stress, which is a potent stimulus of the activation of NO synthase activity.36,37 Taurine supplementation might be a form of antioxidant protection against high fructose–induced detrimental effects on NO-mediated vasorelaxation.

Because of the high intracellular concentrations of taurine and the reactivity of the amino group toward carbonyl groups, taurine could be expected to react with the dicarbonyl intermediate and, thus, scavenge the intracellularly formed reactive carbonyl compounds and glycation intermediates.38 It is postulated that some of the protein crosslinking that occurs in vivo is fructose-induced, which causes fructosylation-dependent protein denaturation.39 Because the conversion of glycated proteins to the more complex denatured proteins involves oxygen free radicals,40 the experimental results indicate that the effects of taurine could be related to its possible oxyradical scavenging properties.

In conclusion, taurine supplementation in regularly exercising subjects has a twofold beneficial effect—prevention of hypertension and an increase in exercise capacity—is a proposal through antioxidant system management and systemic NO optimization. Thus, taurine may rebound in popularity as a fitness supplement in athletes' intent on maximizing performance by virtue of its antioxidant, antifatigue, and antihypertensive properties.

This study was supported by the Korean Ministry of Science and Technology through the Center for Healthcare Technology Development. The authors are grateful to TIPS of CBNU for their careful proofreading of this manuscript.

Disclosure:

The authors declared no conflict of interest.

References

1.
Joyeux-Faure
M
,
Rossini
E
,
Ribuot
C
,
Faure
P
.
Fructose-fed rat hearts are protected against ischemia-reperfusion injury
.
Exp Biol Med (Maywood)
 
2006
;
231
:
456
462
.
2.
Hsieh
PS
.
Attenuation of insulin-mediated pressor effect and nitric oxide release in rats with fructose-induced insulin resistance
.
Am J Hypertens
 
2004
;
17
:
707
711
.
3.
Martinez
FJ
,
Rizza
RA
,
Romero
JC
.
High-fructose feeding elicits insulin resistance, hyperinsulinism, and hypertension in normal mongrel dogs
.
Hypertension
 
1994
;
23
:
456
463
.
4.
Anuradha
CV
,
Balakrishnan
SD
.
Taurine attenuates hypertension and improves insulin sensitivity in the fructose-fed rat, an animal model of insulin resistance
.
Can J Physiol Pharmacol
 
1999
;
77
:
749
754
.
5.
Xu
YJ
,
Arneja
AS
,
Tappia
PS
,
Dhalla
NS
.
The potential health benefits of taurine in cardiovascular disease
.
Exp Clin Cardiol
 
2008
;
13
:
57
65
.
6.
Hu
J
,
Xu
X
,
Yang
J
,
Wu
G
,
Sun
C
,
Lv
Q
.
Antihypertensive effect of taurine in rat
.
Adv Exp Med Biol
 
2009
;
643
:
75
84
.
7.
Jeon
SH
,
Lee
MY
,
Rahman
MM
,
Kim
SJ
,
Kim
GB
,
Park
SY
,
Hong
CU
,
Kim
SZ
,
Kim
JS
,
Kang
HS
.
The antioxidant, taurine reduced lipopolysaccharide (LPS)-induced generation of ROS, and activation of MAPKs and Bax in cultured pneumocytes
.
Pulm Pharmacol Ther
 
2009
;
22
:
562
566
.
8.
Messina
SA
,
Dawson
R
Jr
.
Attenuation of oxidative damage to DNA by taurine and taurine analogs
.
Adv Exp Med Biol
 
2000
;
483
:
355
367
.
9.
Militante
JD
,
Lombardini
JB
.
Treatment of hypertension with oral taurine: experimental and clinical studies
.
Amino Acids
 
2002
;
23
:
381
393
.
10.
Arakawa
K
.
Exercise, a measure to lower blood pressure and reduce other risks
.
Clin Exp Hypertens
 
1999
;
21
:
797
803
.
11.
Miyachi
M
,
Yazawa
H
,
Furukawa
M
,
Tsuboi
K
,
Ohtake
M
,
Nishizawa
T
,
Hashimoto
K
,
Yokoi
T
,
Kojima
T
,
Murate
T
,
Yokota
M
,
Murohara
T
,
Koike
Y
,
Nagata
K
.
Exercise training alters left ventricular geometry and attenuates heart failure in dahl salt-sensitive hypertensive rats
.
Hypertension
 
2009
;
53
:
701
707
.
12.
Missault
LH
,
Duprez
DA
,
Brandt
AA
,
de Buyzere
ML
,
Adang
LT
,
Clement
DL
.
Exercise performance and diastolic filling in essential hypertension
.
Blood Press
 
1993
;
2
:
284
288
.
13.
Thorburn
AW
,
Storlien
LH
,
Jenkins
AB
,
Khouri
S
,
Kraegen
EW
.
Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats
.
Am J Clin Nutr
 
1989
;
49
:
1155
1163
.
14.
Dai
S
,
McNeill
JH
.
Fructose-induced hypertension in rats is concentration- and duration-dependent
.
J Pharmacol Toxicol Methods
 
1995
;
33
:
101
107
.
15.
Hu
ML
,
Louie
S
,
Cross
CE
,
Motchnik
P
,
Halliwell
B
.
Antioxidant protection against hypochlorous acid in human plasma
.
J Lab Clin Med
 
1993
;
121
:
257
262
.
16.
Lang
CA
,
Naryshkin
S
,
Schneider
DL
,
Mills
BJ
,
Lindeman
RD
.
Low blood glutathione levels in healthy aging adults
.
J Lab Clin Med
 
1992
;
120
:
720
725
.
17.
Shaik
IH
,
Mehvar
R
.
Rapid determination of reduced and oxidized glutathione levels using a new thiol-masking reagent and the enzymatic recycling method: application to the rat liver and bile samples
.
Anal Bioanal Chem
 
2006
;
385
:
105
113
.
18.
Lord-Fontaine
S
,
Averill-Bates
DA
.
Heat shock inactivates cellular antioxidant defenses against hydrogen peroxide: protection by glucose
.
Free Radic Biol Med
 
2002
;
32
:
752
765
.
19.
Behr
J
,
Maier
K
,
Degenkolb
B
,
Krombach
F
,
Vogelmeier
C
.
Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression
.
Am J Respir Crit Care Med
 
1997
;
156
:
1897
1901
.
20.
Schalkwijk
CG
,
Stehouwer
CD
,
van Hinsbergh
VW
.
Fructose-mediated non-enzymatic glycation: sweet coupling or bad modification
.
Diabetes Metab Res Rev
 
2004
;
20
:
369
382
.
21.
Kim
C
,
Cha
YN
.
Production of reactive oxygen and nitrogen species in phagocytes is regulated by taurine chloramine
.
Adv Exp Med Biol
 
2009
;
643
:
463
472
.
22.
Dawson
R
Jr
,
Biasetti
M
,
Messina
S
,
Dominy
J
.
The cytoprotective role of taurine in exercise-induced muscle injury
.
Amino Acids
 
2002
;
22
:
309
324
.
23.
Miyazaki
T
,
Matsuzaki
Y
,
Ikegami
T
,
Miyakawa
S
,
Doy
M
,
Tanaka
N
,
Bouscarel
B
.
Optimal and effective oral dose of taurine to prolong exercise performance in rat
.
Amino Acids
 
2004
;
27
:
291
298
.
24.
Hamilton
EJ
,
Berg
HM
,
Easton
CJ
,
Bakker
AJ
.
The effect of taurine depletion on the contractile properties and fatigue in fast-twitch skeletal muscle of the mouse
.
Amino Acids
 
2006
;
31
:
273
278
.
25.
Baron
AD
,
Brechtel-Hook
G
,
Johnson
A
,
Hardin
D
.
Skeletal muscle blood flow. A possible link between insulin resistance and blood pressure
.
Hypertension
 
1993
;
21
:
129
135
.
26.
Nandhini
AT
,
Anuradha
CV
.
Hoe 140 abolishes the blood pressure lowering effect of taurine in high fructose-fed rats
.
Amino Acids
 
2004
;
26
:
299
303
.
27.
Kulakowski
EC
,
Maturo
J
.
Hypoglycemic properties of taurine: not mediated by enhanced insulin release
.
Biochem Pharmacol
 
1984
;
33
:
2835
2838
.
28.
Robertson
JD
,
Maughan
RJ
,
Duthie
GG
,
Morrice
PC
.
Increased blood antioxidant systems of runners in response to training load
.
Clin Sci
 
1991
;
80
:
611
618
.
29.
Franzoni
F
,
Plantinga
Y
,
Femia
FR
,
Bartolomucci
F
,
Gaudio
C
,
Regoli
F
,
Carpi
A
,
Santoro
G
,
Galetta
F
.
Plasma antioxidant activity and cutaneous microvascular endothelial function in athletes and sedentary controls
.
Biomed Pharmacother
 
2004
;
58
:
432
436
.
30.
Magalhães
J
,
Ferreira
R
,
Marques
F
,
Olivera
E
,
Soares
J
,
Ascensão
A
.
Indoor climbing elicits plasma oxidative stress
.
Med Sci Sports Exerc
 
2007
;
39
:
955
963
.
31.
Pialoux
V
,
Mounier
R
,
Rock
E
,
Mazur
A
,
Schmitt
L
,
Richalet
JP
,
Robach
P
,
Coudert
J
,
Fellmann
N
.
Effects of acute hypoxic exposure on prooxidant/antioxidant balance in elite endurance athletes
.
Int J Sports Med
 
2009
;
30
:
87
93
.
32.
Veskoukis
AS
,
Nikolaidis
MG
,
Kyparos
A
,
Kokkinos
D
,
Nepka
C
,
Barbanis
S
,
Kouretas
D
.
Effects of xanthine oxidase inhibition on oxidative stress and swimming performance in rats
.
Appl Physiol Nutr Metab
 
2008
;
33
:
1140
1154
.
33.
Chicco
AJ
,
McCune
SA
,
Emter
CA
,
Sparagna
GC
,
Rees
ML
,
Bolden
DA
,
Marshall
KD
,
Murphy
RC
,
Moore
RL
.
Low-intensity exercise training delays heart failure and improves survival in female hypertensive heart failure rats
.
Hypertension
 
2008
;
51
:
1096
1102
.
34.
Goldfarb
AH
,
Bloomer
RJ
,
McKenzie
MJ
.
Combined antioxidant treatment effects on blood oxidative stress after eccentric exercise
.
Med Sci Sports Exerc
 
2005
;
37
:
234
239
.
35.
Zhen
J
,
Lu
H
,
Wang
XQ
,
Vaziri
ND
,
Zhou
XJ
.
Upregulation of endothelial and inducible nitric oxide synthase expression by reactive oxygen species
.
Am J Hypertens
 
2008
;
21
:
28
34
.
36.
Banfi
G
,
Malavazos
A
,
Iorio
E
,
Dolci
A
,
Doneda
L
,
Verna
R
,
Corsi
MM
.
Plasma oxidative stress biomarkers, nitric oxide and heat shock protein 70 in trained elite soccer players
.
Eur J Appl Physiol
 
2006
;
96
:
483
486
.
37.
Green
DJ
,
Maiorana
A
,
O'Driscoll
G
,
Taylor
R
.
Effect of exercise training on endothelium-derived nitric oxide function in humans
.
J Physiol (Lond)
 
2004
;
561
:
1
25
.
38.
Halliwell
B
.
Oxidative stress markers in human disease: application to diabetes and to evaluation of the effects of antioxidants
. in
Packer
L
,
Rosen
P
,
Tritschler
HJ
,
King
GL
,
Azzi
A
(eds),
Antioxidants in Diabetes Management
.
Marcel Decker
:
New York
,
2000
, pp.
33
52
.
39.
McPherson
JD
,
Shilton
BH
,
Walton
DJ
.
Role of fructose in glycation and cross-linking of proteins
.
Biochemistry
 
1988
;
27
:
1901
1907
.
40.
Namiki
M
,
Oka
M
,
Otsuka
M
,
Miyazawa
T
,
Fujimoto
K
,
Namiki
K
.
Chemiluminescence developed at an early stage of Maillard reaction
. In
Labuza
TP
,
Monnier
V
,
Baynes
J
,
O'Brien
J
(eds),
Maillard Reaction in Chemistry, Food, and Health
.
Royal Society of Chemistry Publishers
:
England
,
1994
, pp.
88
94
.