taurine

As2O3 caused autophagosome accumulated in livers

To investigate whether autophagy was involved in As2O3-induced toxicity, we utilized transmission electron microscopy to observe the ultrastructure in As2O3-treatedlivers. Morphological hallmark of autophagy was the presence of autophagosomes (). Quantification of the autophagosomes numbers per cell demonstrated that As2O3 increased autophagosomes number significantly and in a dose-dependent manner. The number of autophagosomes in As2O3-treated rats was obviously decreased by pretreatment with Tau ().

As2O3 activated autophagy in offsprings’ livers

In this study, we evaluated the expression of autophagy biomarkers, LC3-II and P62, by Western blot analysis (). The level of LC3-II was increased dramatically and the level of P62 was decreased in As2O3-treated livers as shown in Western blot assay. After pretreatment with Tau, the expression of LC3-II was decreased and the expression of P62 was increased dramatically in As2O3-treated cells (), this gave us a clue to investigate the correspondence of autophagy and cytotoxicity at different As2O3 concentration and whether Tau could protect against the autophagy induced by As2O3.

As2O3 reduced the expression of PPARγ in offsprings’ livers

PPARγ was a metabolism related protein in livers. The expression of PPARγ was decreased in As2O3-treated offsprings’ livers (). Tau could protect against the reduction of PPARγ induced by As2O3 in offsprings’ livers ().

As2O3 accelerated Malonic Dialdehyde (MDA) level in offsprings’ livers

As2O3 could induce autophagy through ROS generation in vitro. To investigate the level of oxidative stress, we used MDA test kit to measure the level of MDA. We found that the level of MDA was increased significantly after treatment with As2O3. After pretreatment with Tau, the level of MDA was decreased in the livers of As2O3-treated rats (). It suggested that treatment with As2O3 could accelerate the generation of ROS, and pretreatment with Tau could withstand the oxidative stress induced by As2O3.

Tau reduced cell death of As2O3-treated HepG2 cells

We found that the autophagy in livers was decreased significantly after pretreatment of Tau. To investigate the action of Tau in vitro, the As2O3-treated HepG2 cells were pretreated with Tau at a concentration of 20 μM. The cell viability was elevated significantly (). It suggested that Tau reduced the cell death in As2O3-treated HepG2 cells.

RGS and Tau reduced autophagy in As2O3-treated HepG2 cells

In the study, the level of LC3-II was increased significantly and the expression of P62 was decreased in As2O3-treated HepG2 cells (). After pretreatment with RGS, we found that autophagy was inhibited in As2O3-treated cells (), suggesting that inhibition of PPARγ contributed to As2O3-induced autophagy. The level of autophagy was decreased after pretreatment with Tau in As2O3-treated cells (), suggesting that Tau could protect hepatocytes against As2O3 through modulating PPARγ–autophagy pathway.

Abstract

Taurine (TAU) has been shown to improve exercise time to exhaustion and 3-km running performance; however, no studies have considered the effect of acute TAU ingestion on short duration cycling time trial (TT) performance. The aim of this study was to determine the effects of a single oral acute dose of 1000 mg of TAU on a laboratory simulated 4-km cycling TT. Eleven trained male cyclists performed three, 4-km TTs. The first of the trials was a familiarisation, followed by two subsequent trials which were performed two hours after the consumption of either 1000 mg of TAU or placebo (P), using a double-blind randomised crossover design. Capillary blood samples were obtained prior to the start and immediately after each TT for the measurement of lactate, pH and HCO3 −. There was no effect of TAU (p = 0.731, d = 0.151) on performance (390 ± 27 and 388 ± 21 s for TAU and P, respectively), nor were there any condition main effects for VO2, lactate, pH, or HCO3 − (p > 0.05) despite post TT changes in lactate (7.3 ± 2.5 mmol l−1, p < 0.001, d = 2.86, 7.6 ± 2.0 mmol l−1 p < 0.001, d = 3.75); pH (−0.255 ± 0.1, p < 0.001, d = 2.62, −0.258 ± 0.09, p < 0.001, d = 2.87); HCO3 − (−13.58 ± 2.7 mmol l−1, p < 0.001, d = 5.04 vs. −13.36 ± 2.3, p < 0.001, d = 5.72 for TAU and P, respectively). The findings of this study suggest that a pre-exercise dose of 1000 mg TAU offers no performance advantage during 4-km TT nor does it alter the blood buffering responses in trained cyclists.

Method

Following ethical approval, health screening and informed consent, 11 male trained (De Pauw et al. ) cyclists (mean ± SD age 34.6 ± 11.5 years, height 178.1 ± 5.2 cm, weight 74.8 ± 6.2 kg and body fat 15.5 ± 4.6 %, training >3 h week−1 and at least 2 years’ racing experience) performed three, 4-km TTs on a CompuTrainer Pro cycle ergometer (RacerMate, Seattle, USA). The CompuTrainer was fitted with each participants own bicycle, which was then calibrated in accordance with the manufacturers guidelines. The cyclists were allowed to use either a road or TT bike, but they had to use the same machine and gear ratios for each trial. Participants were instructed to adopt a position on the handlebars which was most comfortable. Using this method, 4-km laboratory TTs have previously been shown to have a coefficient of variation of 1.6 % (Altareki et al. ) for performance times and produce reliable pacing strategies (Stone et al. ) in similar participant populations. Body composition data were measured using air-displacement plethysmography (BodPod V4.2.0, Life Measurement Inc., USA). Prior to each TT, participants were instructed to abstain from any food intake in the preceding 3 h and to adhere to their normal nutritional intake strategy. Nutritional intake was recorded for the 24-h period prior to attending the initial laboratory visit, and replicated on each subsequent occasion. For the preceding 24-h period, participants were also instructed to avoid performing any exercise. Pre-exercise urine samples were obtained to measure urine osmolality using a portable osmometer (Osmocheck, Vitech Scientific, West Sussex, UK) which has previously been shown to be both valid and reliable (Sparks and Close ). This was to ensure that this index of hydration status was consistent prior to each trial.

Experimental procedures

Participants performed a standardised warm-up which required them to cycle at a self-selected intensity for 5 min. This was replicated prior to each subsequent TT. Each laboratory session was performed at the same time of day to minimise the potential effects of circadian variations (Souissi et al. ). The first laboratory visit was a familiarisation TT as this has been shown to improve subsequent test–retest pacing strategy reliability (Ansley et al. ). This initial trial was followed by two experimental trials that took place between five and 7 days apart, which was chosen to limit the confounding effects of fatigue and potential changes in training status. All trials commenced 2 h after the consumption of either a 500 ml drink containing only water (Buxton still mineral water, UK), in the case of the familiarisation and the placebo trials, or after the consumption of 500 ml water containing 1000 mg of TAU (Acrōs Organics, Geel, Belgium). This pre-exercise consumption period was used to elicit peak plasma TAU concentrations at the start of the time trial (Galloway et al. ). The placebo and TAU TTs were conducted using a double-blind randomised crossover design. This dose was chosen because it has previously been shown to improve high intensity running performance in well-trained runners (Balshaw et al. ) and represents the typical dose in many commercially available energy and stimulant drinks. Data were downloaded from the ergometer software at a frequency of 37 Hz to determine each 500 m split time, speed and overall performance time.

Results

There were no main effects for experimental condition on blood lactate (mean difference = 0.19 mmol l−1, f = 1.06, CI = −0.22, 0.60, p = 0.33, ηp2 = 0.10), pO2 (mean difference = 0.10 kPa, f = 0.25, CI = −0.35, 0.56, p = 0.63, pη2 = 0.03), pCO2 (mean difference = 0.01 kPa, f = 0.01, CI = −0.26, 0.24, p = 0.93, ηp2 = 0.01), pH (mean difference = 0.003 pH units, f = 0.12, CI = −0.02, 0.01, p = 0.73, ηp2 = 0.010), nor HCO3 (mean difference = 0.17 mmol l−1, f = 0.50, CI = −0.37, 0.72, p = 0.50, ηp2 = 0.05), but there were significant main effects for time on all of the blood parameters (Table ). This was characterised by post exercise increases in blood lactate (mean difference = 7.41 mmol l−1, f = 112.72, CI = 5.85, 8.96, p < 0.001, ηp2 = 0.92) and pO2 (mean difference = 2.67 kPa, f = 148.39, CI = 2.17, 3.17, p < 0.001, ηp2 = 0.94). Conversely pCO2 (mean difference = −1.04 kPa, f = 155.88, CI = −1.23, −0.85, p < 0.001, ηp2 = 0.94) pH (mean difference = −0.26 pH units, f = 77.52, CI = −0.32, −0.19, p < 0.001, ηp2 = 0.89) and HCO3 (mean difference = −13.47 mmol l−1, f = 334.08, CI = −15.12, −11.83, p < 0.001, ηp2 = 0.97) were all significantly lowered (Table ) following the completion of the TTs. Base excess (Table ) was also consequently unaffected by taurine ingestion (mean difference = 0.18 mEq l−1, f = 0.51, CI = −0.74, 0.38, p = 0.49, ηp2 = 0.05), but significant decreases were observed following the 4-km TTs (mean difference = −16.04 mEq l−1, f = 222.51, CI = −18.44, −13.65, p < 0.001, ηp2 = 0.96).Table 1Mean (±SD) pre and post time trial blood parameter responses to the experimental conditionsParameterTaurinePlaceboLactate (mmol l−1) Pre0.9 ± 0.30.9 ± 0.5 Post8.2 ± 2.4*8.6 ± 2.0*pO2 (kPa) Pre9.6 ± 0.79.8 ± 1.1 Post12.3 ± 0.8*12.4 ± 0.6*pCO2 (kPa) Pre5.4 ± 0.35.3 ± 0.4 Post4.3 ± 0.3*4.3 ± 0.4*pH Pre7.42 ± 0.027.42 ± 0.01 Post7.16 ± 0.1*7.16 ± 0.08*HCO3 (mmol l−1) Pre25.5 ± 0.125.2 ± 1.6 Post11.9 ± 2.7*11.9 ± 2.3*Base Excess (mEq l−1) Pre1.29 ± 1.11.01 ± 1.6 Post−14.84 ± 3.9*−14.96 ± 3.2** Denotes significant post time trial changes (p < 0.001)