Radiation therapy along with chemotherapy and surgery remain the main cancer treatments. Radiotherapy can be applied to patients externally (external beam radiotherapy) or internally (brachytherapy and radioisotope therapy). Previously, nanoencapsulation of radioactive crystals within carbon nanotubes, followed by end-closing, resulted in the formation of nanocapsules that allowed ultrasensitive imaging in healthy mice. Herein we report on the preparation of nanocapsules initially sealing “cold” isotopically enriched samarium (152Sm), which can then be activated on demand to their “hot” radioactive form (153Sm) by neutron irradiation. The use of “cold” isotopes avoids the need for radioactive facilities during the preparation of the nanocapsules, reduces radiation exposure to personnel, prevents the generation of nuclear waste, and evades the time constraints imposed by the decay of radionuclides. A very high specific radioactivity is achieved by neutron irradiation (up to 11.37 GBq/mg), making the “hot” nanocapsules useful not only for in vivo imaging but also therapeutically effective against lung cancer metastases after intravenous injection. The high in vivo stability of the radioactive payload, selective toxicity to cancerous tissues, and the elegant preparation method offer a paradigm for application of nanomaterials in radiotherapy.

Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). These in vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.

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The hepato-steatogenic compound ethionine has been used to investigate the correlations between in vivo and in vitro toxicity data. The aim was to find a suitable model of toxicity in hepatocyte suspensions or monolayers in vitro, which could predict the known toxicity of ethionine in vivo and which could be implemented in screening compounds of unknown toxicity. Thus a variety of markers of cytotoxicity, metabolic competence and liver-specific functions were investigated in rat hepatocyte suspensions and monolayers and compared with in vivo data in the rat. The following markers were measured in the appropriate system: (1) Neutral red uptake; 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction; lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) leakage (cytotoxicity). (2) ATP levels, protein synthesis and glutathione (GSH) levels (metabolic competence). (3) Urea and triglyceride synthesis and beta-oxidation (liver specific functions). Ethionine (0-30 mM) did not affect the markers of direct cytotoxicity, except neutral red uptake, which was reduced by 18 and 30 mM ethionine after 20 h in culture. ATP and GSH depletion occurred in hepatocyte suspensions at the highest concentrations of ethionine (20 and 30 mM) after 1 h. In monolayers, GSH levels were reduced after 4 h, but not 20 h. Urea synthesis was increased in hepatocyte suspensions from 1 to 3 h by 10-30 mM ethionine and reduced after 20 h in cultured hepatocytes (18-30 mM). Protein synthesis was reduced and beta-oxidation was increased in ethionine-treated hepatocyte suspensions. Unfortunately, there was no measurable effect on triglyceride accumulation within cells (the major biochemical change in vivo) in either system. Ethionine treated hepatocytes in suspension showed the same rate of triglyceride synthesis and transportation out of cells as control cells. Thus, hepatocyte suspensions were able to mimic the early biochemical effects of ethionine in vivo (ATP and GSH depletion, inhibition of protein synthesis) and some effects on urea synthesis, but monolayer cultures appeared to be less sensitive to the toxicity of ethionine. However, neither in vitro system was able to model the effects of ethionine on the accumulation of triglycerides in vivo.

We have previously reported on the changes in urinary taurine levels in rats following treatment with some hepatotoxic agents and compounds reported to affect protein synthesis. This study follows the time course of the elevation of urinary taurine after treatment of rats with cycloheximide which was maximal 8-12 h alter dosing and was dose related. [(3)H]-leucine incorporation into proteins was used as an indicator of protein synthesis. There was a significant reduction in [(3)H]-leucine incorporation into acid precipitable proteins 8 h but not 24 h after dosing. The reduction in incorporation was negatively correlated with the raised levels of both serum and urinary taurine 8 h after dosing. Liver glutathione was raised both 8 and 24 h after dosing rats and liver taurine was significantly reduced at 8 h. It is suggested that measuring urinary taurine in collections made continuously might provide a simple, non-invasive biomarker for monitoring the effects of xenobiotics or other external stimuli on the status of protein synthesis.