Protective Role of Taurine against Arsenic-Induced Mitochondria-Dependent Hepatic Apoptosis via the Inhibition of PKCδ-JNK Pathway

BACKGROUND: Oxidative stress-mediated hepatotoxic effect of arsenic (As) is mainly due to the depletion of glutathione (GSH) in liver. Taurine, on the other hand, enhances intracellular production of GSH. Little is known about the mechanism of the beneficial role of taurine in As-induced hepatic pathophysiology. Therefore, in the present study we investigated its beneficial role in As-induced hepatic cell death via mitochondria-mediated pathway. METHODOLOGY/PRINCIPAL FINDINGS: Rats were exposed to NaAsO(2) (2 mg/kg body weight for 6 months) and the hepatic tissue was used for oxidative stress measurements. In addition, the pathophysiologic effect of NaAsO(2) (10 microM) on hepatocytes was evaluated by determining cell viability, mitochondrial membrane potential and ROS generation. As caused mitochondrial injury by increased oxidative stress and reciprocal regulation of Bcl-2, Bcl-xL/Bad, Bax, Bim in association with increased level of Apaf-1, activation of caspase 9/3, cleavage of PARP protein and ultimately led to apoptotic cell death. In addition, As markedly increased JNK and p38 phosphorylation with minimal disturbance of ERK. Pre-exposure of hepatocytes to a JNK inhibitor SP600125 prevented As-induced caspase-3 activation, ROS production and loss in cell viability. Pre-exposure of hepatocytes to a p38 inhibitor SB2035, on the other hand, had practically no effect on these events. Besides, As activated PKCdelta and pre-treatment of hepatocytes with its inhibitor, rottlerin, suppressed the activation of JNK indicating that PKCdelta is involved in As-induced JNK activation and mitochondrial dependent apoptosis. Oral administration of taurine (50 mg/kg body weight for 2 weeks) both pre and post to NaAsO(2) exposure or incubation of the hepatocytes with taurine (25 mM) were found to be effective in counteracting As-induced oxidative stress and apoptosis. CONCLUSIONS/SIGNIFICANCE: Results indicate that taurine treatment improved As-induced hepatic damages by inhibiting PKCdelta-JNK signalling pathways. Therefore taurine supplementation could provide a new approach for the reduction of hepatic complication due to arsenic poisoning

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Not AvailableCharacterization of soil water retention, e.g., water content at field capacity (FC) and permanent wilting point (PWP) over a landscape plays a key role in efficient utilization of available scarce water resources in dry land agriculture; however, direct measurement thereof for multiple locations in the field is not always feasible. Therefore, pedotransfer functions (PTFs) were developed to estimate soil water retention at FC and PWP for dryland soils of India. A soil database available for Arid Western India (N=370) was used to develop PTFs. The developed PTFs were tested in two independent datasets from arid regions of India (N=36) and an arid region of USA (N=1789). While testing these PTFs using independent data from India, root mean square error (RMSE) was found to be 2.65 and 1.08 for FC and PWP, respectively, whereas for most of the tested ‘established’ PTFs, the RMSE was >3.41 and >1.15, respectively. Performance of the developed PTFs from the independent dataset from USA was comparable with estimates derived from ‘established’ PTFs. For wide applicability of the developed PTFs, a user-friendly soil moisture calculator was developed. The PTFs developed in this study may be quite useful to farmers for scheduling irrigation water as per soil type.Not Availabl

Preparation and Characterization of Silica-Coated Magnetic–Fluorescent Bifunctional Microspheres

<p>Abstract</p> <p>Bifunctional magnetic&#8211;fluorescent composite nanoparticles (MPQDs) with Fe₃O₄MPs and Mn:ZnS/ZnS core&#8211;shell quantum dots (QDs) encapsulated in silica spheres were synthesized through reverse microemulsion method and characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, vibration sample magnetometer, and photoluminescence (PL) spectra. Our strategy could offer the following features: (1) the formation of Mn:ZnS/ZnS core/shell QDs resulted in enhancement of the PL intensity with respect to that of bare Mn:ZnS nanocrystals due to the effective elimination of the surface defects; (2) the magnetic nanoparticles were coated with silica, in order to reduce any detrimental effects on the QD PL by the magnetic cores; and (3) both Fe₃O₄MPs and Mn:ZnS/ZnS core&#8211;shell QDs were encapsulated in silica spheres, and the obtained MPQDs became water soluble. The experimental conditions for the silica coating on the surface of Fe₃O₄nanoparticles, such as the ratio of water to surfactant (<it>R</it>), the amount of ammonia, and the amount of tetraethoxysilane, on the photoluminescence properties of MPQDs were studied. It was found that the silica coating on the surface of Fe₃O₄could effectively suppress the interaction between the Fe₃O₄and the QDs under the most optimal parameters, and the emission intensity of MPQDs showed a maximum. The bifunctional MPQDs prepared under the most optimal parameters have a typical diameter of 35 nm and a saturation magnetization of 4.35 emu/g at room temperature and exhibit strong photoluminescence intensity.</p

Arsenic trioxide: Safety issues and their management

Arsenic trioxide (As2O2) has been used medicinally for thousands of years. Its therapeutic use in leukaemia was described a century ago. Recent rekindling in the interest of As2O3 is due to its high efficacy in acute promyelocytic leukaemia (APL). As2O 3 has also been tested clinically in other blood and solid cancers. Most studies have used intravenous As2O3, although an oral As2O3 is equally efficacious. Side effects of As 2O3 are usually minor, including skin reactions, gastrointestinal upset, and hepatitis. These respond to symptomatic treatment or temporary drug cessation, and do not compromise subsequent treatment with As2O3. During induction therapy in APL, a leucocytosis may occasionally occur, which can be associated with fluid accumulation and pulmonary infiltration. The condition is similar to the APL differentiation syndrome during treatment with all-trans retinoic acid, and responds to cytoreductive treatment and corticosteroids. Intravenous As2O 3 treatment leads to QT prolongation. In the presence of underlying cardiopulmonary diseases or electrolyte disturbances, particularly hypokalaemia and hypomagnesaemia, serious arrhythmias may develop, with torsades du pointes reported in 1% of cases. This may be related to a dose-dependent arsenic-mediated inhibition of potassium ion channels that compromises cardiac repolarization. Because of slow intestinal absorption, oral-As2O 3 gives a lower plasma arsenic concentration, which is associated with lesser QT prolongation and hence a more favorable cardiac safety profile. As2O3 does not appear to enter the central nervous system. However, if the blood brain barrier is breached, elemental arsenic may enter the cerebrospinal fluid. As2O3 is predominantly excreted in the kidneys, and dose adjustment is required when renal function is impaired. © 2008 CPS and SIMM.link_to_OA_fulltex