Taurine Ameliorates Oxidative Stress in Spinal Cords of Diabetic Rats via Keap1-Nrf2 Signaling.

Hyperglycemia associated with diabetes mellitus (DM) causes oxidative stress, which is involved in the onset and development of diabetic neuropathy. Taurine, a powerful antioxidant, is an effective inhibitor of oxidative stress. The present experiment was conducted to explore the effect of taurine treatment on alterations in body weight, blood glucose, oxidative stress, and Keap1-Nrf2 signaling in the spinal cords of DM rats. The DM rat model was established by STZ injection, and taurine was administered in the drinking water. Body weight and blood glucose were recorded during the experiment. The expression of Gap-43 and MBP proteins was examined by Western blot. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were examined as indicators of oxidative stress. The expression of Keap1, Nrf2, and HO-1 gene was examined by real-time PCR. The results showed that compared with the control group, the body weight was decreased, blood glucose was increased, and both Gap-43 and MBP expression were decreased in DM rats, which were all remarkably reversed by taurine treatment. Oxidative stress, as reflected by lower SOD activity and higher MDA concentration, was inhibited in taurine-treated DM rats. Supplemental taurine also downregulated the mRNA level of Keap1, while upregulating Nrf2 and HO-1 mRNA levels. These results showed that taurine inhibits oxidative stress in the spinal cords of DM rats, an effect that might involve the regulation of Keap1-Nrf2 signaling.

Successful treatment of acute promyelocytic leukemia in a 92-year-old man using all-trans retinoic acid combined with oral arsenic: A case report.

RATIONALE: Acute promyelocytic leukemia is a special subtype of acute myeloid leukemia. The incidence of early death and complications is high. An oral regimen of all-trans retinoic acid combined with the realgar-indigo naturalis formula (RIF) without chemotherapy has provided a new strategy for the treatment of these patients. PATIENT CONCERNS: A 92-year-old male patient was admitted to the hospital due to fatigue and oral bleeding. He had no fever or lung infection. Routine blood test showed white blood cell count 1.0 ×109/L, hemoglobin 100 g/L, and platelets 21 × 109/L. Coagulation function indicated fibrinogen 1.02 g/L and D-dimer 2360 ng/mL. And 28% abnormal promyelocytes were observed in peripheral blood. DIAGNOSIS: A bone marrow morphologic, immunophenotypic, cytogenetic, and molecular examination was performed. Routine bone marrow examination showed active proliferation of nucleated cells, with promyelocytes accounting for 91%; immunophenotyping revealed an early myeloid cell population, accounting for approximately 82.4% of all cells. INTERVENTIONS: From February 15, 2020, 25 mg/m2 all-trans retinoic acid was orally administered daily. After the fusion gene result was obtained, oral administration of 60 mg/kg RIF daily began since February 18, 2020. The combination of the 2 agents was given until March 16, 2020. Oral administration of 25 mg/m2 retinoic acid daily began from March 20, 2020 for 2 weeks, and oral administration of 60 mg/kg RIF daily lasted for 4 weeks as the consolidation therapy. During the treatment, the proportion of promyelocytes in peripheral blood, white blood cell count, platelets, coagulation function, liver function, and QT interval were monitored. OUTCOMES: Oral retinoic acid and oral RIF were given without chemotherapy and the patient achieved bone marrow remission after 1 month, and molecular remission was achieved 2 months later. In the early stage of acute promyelocytic leukemia, combined thrombocytopenia and disseminated intravascular coagulation may develop. Platelet and fresh frozen plasma infusion were proactively given until platelets were stabilized above 30 × 109/L, and the coagulation function returned to normal. LESSONS: The regimen was safe and effective, and subsequent treatment did not require hospitalization, which helped to improve the patient's quality of life.

Taurine inhibits neuron apoptosis in hippocampus of diabetic rats and high glucose exposed HT-22 cells via the NGF-Akt/Bad pathway.

Type 2 Diabetes causes learning and memory deficits that might be mediated by hippocampus neuron apoptosis. Studies found that taurine might improve cognitive deficits under diabetic condition because of its ability to prevent hippocampus neuron apoptosis. However, the effect and mechanism is not clear. In this study, we explore the effect and mechanism of taurine on inhibiting hippocampus neuron apoptosis. Sixty male Sprague-Dawley rats were randomly divided into control, T2D, taurine treatment (giving 0.5%, 1%, and 2% taurine in drinking water) groups. Streptozotocin was used to establish the diabetes model. HT-22 cell (hippocampus neurons line) was used for in vitro experiments. Morris Water Maze test was used to check the learning and memory ability, TUNEL assay was used to measure apoptosis and nerve growth factor (NGF); Akt/Bad pathway relevant protein was detected by western blot. Taurine improved learning and memory ability and significantly decreased apoptosis of the hippocampus neurons in T2D rats. Moreover, taurine supplement also inhibited high glucose-induced apoptosis in HT-22 cell in vitro. Mechanistically, taurine increased the expression of NGF, phosphorylation of Trka, Akt, and Bad, as well as reduced cytochrome c release from mitochondria to cytosol. However, beneficial effects of taurine were blocked in the presence of anti-NGF antibody or Akt inhibitor. Taurine could inhibit hippocampus neuron apoptosis via NGF-Akt/Bad pathway. These results provide some clues that taurine might be efficient and feasible candidate for improvement of learning and memory ability in T2D rats.

Hydrogen sulfide lowers hyperhomocysteinemia dependent on cystathionine γ lyase S-sulfhydration in ApoE-knockout atherosclerotic mice.

BACKGROUND AND PURPOSE: Hydrogen sulfide donors can block the cardiovascular injury of hyperhomocysteinemia. H2 S also lowers serum homocysteine in rats with mild hyperhomocysteinemia, but the pharmacological mechanism is unknown. The present study investigated the mechanism(s) involved. EXPERIMENTAL APPROACH: ApoE-knockout mice were fed a Paigen diet and L-methionine in drinking water for 16 weeks to create a mouse model of atherosclerosis with hyperhomocysteinemia. H2 S donors (NaHS and GYY4137) were administered by intraperitoneal injection. We also assayed the H2 S produced (by methylene blue assay and mito-HS [H2 S fluorescence probe]), cystathionine γ lyase (CSE) mRNA and protein expression, and CSE sulfhydration and nitrosylation and its activity. KEY RESULTS: H2 S donor treatment significantly lowered atherosclerotic plaque area, macrophage infiltration, and serum homocysteine level in the mouse model of atherosclerosis with co-existing hyperhomocysteinemia. mRNA and protein levels of CSE, a key enzyme catalyzing homocysteine trans-sulfuration, were down-regulated with hyperhomocysteinemia, and CSE catalytic activity was inhibited. All these effects were reversed with H2 S donor treatment. Hyperhomocysteinemia induced CSE nitrosylation, whereas H2 S sulfhydrated CSE at the same cysteine residues. Nitrosylated CSE decreased and sulfhydrated CSE increased its catalytic and binding activities towards L-homocysteine. Mutation of C252, C255, C307, and C310 residues in CSE abolished CSE nitrosylation or sulfhydration and prevented its binding to L-homocysteine. CONCLUSIONS AND IMPLICATIONS: Sulfhydration or nitrosylation of CSE represents a yin/yang regulation of catalysis or binding to L-homocysteine. H2 S donor treatment enhanced CSE sulfhydration, thus lowering serum L-homocysteine, which contributed in part to the anti-atherosclerosis effects in ApoE-knockout mice with hyperhomocysteinemia.

Taurine Ameliorates Arsenic-Induced Apoptosis in the Hippocampus of Mice Through Intrinsic Pathway.

Our group previously reported that arsenic (As) exposure induced apoptosis in hippocampus neurons. The aim of the present study was to clarify the protective capacity of taurine (Tau) on As-induced neuronal apoptosis and the related mechanism in mouse hippocampus. Mice were divided into: control group, Tau control group, As exposure group and Tau protective group, randomly. The apoptotic rate of mouse hippocampus was determined by TUNEL staining. The levels of Bcl-2 and Bax gene and protein were analyzed by real time RT-PCR and WB, respectively. Furthermore, cytochrome c (Cyt C) release, and the activity of caspase-8 and caspase-3 were also determined. The results showed that Tau treatment induced the decrease of TUNEL-positive cells, prohibited the disturbance of Bcl-2 and Bax expression, and inhibited Cyt C release and caspase-8 and caspase-3 activation significantly. The results indicated that Tau supplement markedly ameliorates As-induced apoptosis by mitochondria-related pathway in mouse hippocampus.

Protection of Taurine Against Impairment in Learning and Memory in Mice Exposed to Arsenic.

To evaluate protection of taurine against arsenic (As)-induced impairment of learning and memory as well as explore its protective mechanism, mice were divided into control, As and taurine protection groups. Mice of As exposure group exposed to drinking water containing 4 ppm As2O3. Mice of taurine protective group received both 4 ppm As2O3 and 150 mg taurine per kilogram. Mice of control group only drank double-distilled water. All animals were treated for 60 days. Morphology of brain was observed by HE staining. Morris water maze (MWM) tests and step-down passive avoidance task were performed to examine cognition function. Moreover, expressions of some genes and proteins related to regulation learning and memory in brain were tested by Real Time RT-PCR and Western Blot. As a result, abnormal morphologic changes in brain tissue and poor performance in cognition functions were observed in As-exposed mice. The expression of TRß protein, a regulator of CaMK IV gene, significantly decreased in brains of As-exposed mice than in controls. By contrast, impairment in learning and memory, change in brain morphology and disturbance in protein expression were significantly mitigated in mice of taurine protective group. Our results suggest that taurine supplementation protects against neurotoxicity induced by As in mice.

Taurine Normalizes the Levels of Se, Cu, Fe in Mouse Liver and Kidney Exposed to Arsenic Subchronically.

To evaluate the benefits of taurine on the homeostasis of trace elements induced by toxic metals, we investigated the concentration of Selenium (Se), Copper (Cu), Iron (Fe) and Manganese (Mn) in mouse liver and kidney after arsenic exposure for 2 months. The experimental animals were divided into control group, arsenic exposure group (1, 2, 4 ppm) and taurine protective group randomly. Concentrations of serum, liver and kidney trace elements such as Se, Cu, Fe, Mn were measured by Inductively Coupled Plasma-Mass Spectrometry. Our results showed that the concentration of Cu was higher, however, the concentration of Se and Fe was lower in mice liver and kidney exposed to arsenic. The levels of Se, Cu, Fe were alleviated by co-administered with taurine. Furthermore, there was no difference in the concentration of Mn between the three groups. Our finding suggests that taurine may relieve the disturbed levels of Se, Cu and Fe in liver and kidney induced by arsenic.

Protection of Taurine Against Arsenic-Induced DNA Damage of Mice Kidneys.

The purpose of this study was to explore the protective capacity of taurine on arsenic (As)-induced neurotoxicity. Thirty mice were used and ten rats in each group. We treated the As exposure group with 4 ppm As2O3 for 60 days by drinking water and the protective group with 4 ppm As2O3 and 150 mg/kg taurine. Drinking water was only given in the control group. Pathologic changes and DNA damage in the mice kidney were examined by HE staining, immunohistochemistry and comet assay. Abnormal morphological changes were found in the kidney of As exposed mouse. Moreover, 8-hydroxy-2-deoxyguanosine (8-OHdG) expression and comet number, tail moment, and tail length of comet were markedly elevated in the As intoxication mice. However, histopathological changes and low expression of 8-OHdG were shown in the protective group. Our results indicate that supplementation of taurine protects against the histopathologic changes and DNA damage of mouse kidneys in As exposure group.