The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD.

https://www.physiology.org/doi/pdf/10.1152/ajpregu.00677.2010

Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

Although recent studies indicate that renal ischemic preconditioning (IPC) protects the kidney from ischemia-reperfusion (I/R) injury, the precise protective mechanism remains unclear. In the current study, we investigated whether early IPC could upregulate hypoxia inducible transcription factor-1α (HIF-1α) expression and could reduce endoplasmic reticulum (ER) stress after renal I/R and whether pharmacological inhibition of nitric oxide (NO) production would abolish these protective effects. Kidneys of Wistar rats were subjected to 60 min of warm ischemia followed by 120 min of reperfusion (I/R group), or to 2 preceding cycles of 5 min ischemia and 5 min reperfusion (IPC group), or to intravenously injection of NG-nitro-L-arginine methylester (L-NAME, 5 mg/kg) 5 min before IPC (L-NAME+IPC group). The results of these experimental groups were compared to those of a sham-operated group. Sodium reabsorption rate, creatinine clearance, plasma lactate dehydrogenase (LDH) activity, tissues concentrations of malonedialdehyde (MDA), HIF-1α and nitrite/nitrate were determined. In addition, Western blot analyses were performed to identify the amounts of Akt, endothelial nitric oxide synthase (eNOS) and ER stress parameters. IPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely, IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1α levels as compared to I/R group. Moreover, our results showed that IPC increased the relative amounts of glucose-regulated protein 78 (GRP78) and decreased those of RNA activated protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 4 (ATF4) and TNF-receptor-associated factor 2 (TRAF2) as judged to I/R group. However, pre treatment with L-NAME abolished these beneficial effects of IPC against renal I/R insults. These findings suggest that early IPC protects kidney against renal I/R injury via reducing oxidative and ER stresses. These effects are associated with phosphorylation of Akt, eNOS activation and NO production contributing thus to HIF-1α stabilization. The beneficial impact of IPC was abolished when NO production is inhibited before IPC application.

/pdf/ischemic-preconditioning-reduces-endoplasmic-reticulum-y6i2tc76dm.pdf

Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide

Cysteine sulfinic acid decarboxylase (Csad) is the rate-limiting enzyme in the de novo biosynthesis of taurine. There are a number of physiological roles of taurine, such as bile salt synthesis, osmoregulation, lipid metabolism, and oxidative stress inhibition. To investigate the role of de novo synthesis of taurine during embryonic development, zebrafish csad was cloned and functionally analyzed. Semi-quantitative RT-PCR showed that csad transcripts are maternally deposited, while whole-mount in situ hybridization demonstrated that csad is expressed in yolk syncytial layer and various embryonic tissues such as notochord, brain, retina, pronephric duct, liver, and pancreas. Knockdown of csad significantly reduced the embryonic taurine level, and the affected embryos had increased early mortality and cardiac anomalies. mRNA coinjection and taurine supplementation rescued the cardiac phenotypes suggesting that taurine originating from the de novo synthesis pathway plays a role in cardiac development. Our findings indicated that the de novo synthesis pathway via Csad plays a critical role in taurine homeostasis and cardiac development in zebrafish early embryos.

Taurine homeostasis requires de novo synthesis via cysteine sulfinic acid decarboxylase during zebrafish early embryogenesis

Growing evidence suggests that ozone (O3) protects the host against pathological conditions mediated by reactive oxygen species by increasing the activity of antioxidant enzymes. The purpose of the present study was to examine the effect of O3 on intestinal recovery and enterocyte turnover after intestinal ischemia–reperfusion (IR) injury in rats. Male Sprague–Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy; (2) sham-O3 rats underwent laparotomy and were treated with an ozone/oxygen mixture intraperitoneally and intraluminally (50 %/50 %); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 min followed by 48 h of reperfusion, and (4) IR-O3 rats underwent IR and were treated with an ozone/oxygen mixture similar to group 2. Intestinal structural changes, Park’s injury score, enterocyte proliferation and enterocyte apoptosis were determined 48 h following IR. Western blot was used to determine ERK and Bax protein levels. A non-parametric Kruskal–Wallis ANOVA test was used for statistical analysis with p < 0.05 considered statistically significant. Treatment of IR rats with O3 resulted in a significant increase in mucosal weight in jejunum (70 %) and ileum (32 %), mucosal DNA (twofold increase) and protein (35 %) in ileum, villus height and crypt depth in jejunum (61 and 16 %, correspondingly) and ileum (31 and 43 %, correspondingly) compared to IR animals. IR-O3 rats also had a significantly lower intestinal injury score as well as a lower apoptotic index in jejunum and ileum compared and IR animals. A significant increase in cell proliferation rates in IR-O3 animals was accompanied by increased levels of p-ERK protein. Treatment with ozone prevents intestinal mucosal damage, stimulates cell proliferation and inhibits programmed cell death following intestinal IR in a rat.

Effect of taurine on intestinal recovery following intestinal ischemia-reperfusion injury in a rat

Role of angiotensin-converting enzyme (ACE and ACE2) imbalance on tourniquet-induced remote kidney injury in a mouse hindlimb ischemia-reperfusion model.

Background and purpose CHOP is a C/EBP family transcription factor involved in endoplasmic reticulum (ER) stress-mediated apoptosis. Several studies have demonstrated that ischemia reperfusion resu...

Taurine protects against lung damage following limb ischemia reperfusion in the rat by attenuating endoplasmic reticulum stress-induced apoptosis.

Stress hyperglycemia is a strong neuroendocrine reaction in thehypothalamic pituitary adrenal cortex under severe infection, trauma, burns,hemorrhage, surgery and other harmful stimulated, resulting in increasedsecretion of counter-regulatory hormones. These hormones promotedthe production of sugar and cause glucose metabolism disorders withcytokines and insulin resistance. In this condition, the production of sugarexceeds the utilization of sugar by the tissues, which eventually leads to anincrease in blood glucose levels in plasma. In the intensive care unit, stresshyperglycemia is very common and can occur in patients with or withoutdiabetes. The incidence is as high as 96%, and it is an independent factorin the death of critically ill patients. Hyperglycemia not only prolongsthe hospitalization time, mechanical ventilation time and increased theincidence of serious infections in critically ill patients, but can also leadto the occurrence of type 2 diabetes. Therefore, it is very important tolearn the pathological mechanism of stress hyperglycemia, the harm ofhyperglycemia and blood sugar management.

Jianyi Pu

Papers

Taurine protects against lung damage following limb ischemia reperfusion in the rat by attenuating endoplasmic reticulum stress-induced apoptosis.

Stress Hyperglycemia: A Problem that Cannot be Ignored