Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer.

The antineoplastic effects of 5-hydroxytryptamine (5-HT) receptor antagonists have been shown in previous studies. However, the exact underlying mechanisms mediating these antineoplastic effects are unclear. In the present study, we assessed the antineoplastic effects of tropisetron, a 5-HT receptor antagonist, in an experimental model of lung cancer in BALB/c mouse. Lewis lung carcinoma cell line was used to induce lung cancer. Mice were divided into four groups (n = 6) as follows: tumor-bearing mice + tropisetron (5 mg/kg intraperitoneally [IP]), tumor-bearing mice + tropisetron (10 mg/kg IP), tumor-bearing mice + saline, healthy mice + tropisetron (10 mg/kg). Tumor burden, interferon-γ (IFN-γ), interleukin (IL)-4, pathological response, Ki-67, and E-cadherin were assessed using enzyme-linked immunosorbent assay, and real-time polymerase chain reaction. Comet assay was used to assess DNA toxicity. Tropisetrone-treated animals (either 5 or 10 mg/kg) showed significantly lower tumor sizes at the day 24th after tumor induction. Tropisetron received animals also showed significantly higher levels of IFN-γ, E-cadherin, pathologic response, and necrotic cells compared to the saline-treated counterparts. In addition, the levels of IL-4, and Ki-67 were significantly lower in tropisetrone treated mice in comparison with control. Furthermore, tropisteron coadministration signifcantly reduced H2 O2 -induced DNA toxicity while treatment with tropisteron alone showed no adverse effect on DNA. Tropisetrone can be used as a potential antineoplastic drug in lung cancer. This agent can promote its antineoplastic effects in part through modulating inflammatory and proliferating markers.

Prevention of phosphine-induced cytotoxicity by nutrients in HepG2 cells.

BACKGROUND & OBJECTIVES: Phosphides used as an insecticide and rodenticide, produce phosphine (PH3) which causes accidental and intentional poisoning cases and deaths. There is no specific treatment or antidote available for PH3poisoning. It is suggested that PH3-induced toxicity is associated with adenosine triphosphate (ATP) depletion; therefore, in this study the effect of some nutrients was evaluated on PH3cytotoxicity in a cell culture model. METHODS: PH3was generated from reaction of zinc phosphide (10 mM) with water in the closed culture medium of HepG2 cells, and cytotoxicity was measured after one and three hours of incubation. ATP, glutathione (GSH) and lipid peroxidation were also assessed at one or three hours post-incubation. ATP suppliers including dihydroxyacetone, glyceraldehyde and fructose were added to the culture medium 10 min before PH3generation to prevent or reduce phosphine-induced cytotoxicity. RESULTS: Phosphine caused about 30 and 66 per cent cell death at one and three hours of incubation, respectively. ATP content of the cells was depleted to 14.7 per cent of control at one hour of incubation. ATP suppliers were able to prevent cytotoxicity and ATP depletion induced by PH3. Dihydroxyacetone, α-ketoglutarate, fructose and mannitol restored the ATP content of the cells from 14.7 per cent to about 40 , 34 , 32 and 30 per cent, respectively. Lipid peroxidation and GSH depletion were not significantly induced by zinc phosphide in this study. INTERPRETATION & CONCLUSIONS: The results supported the hypothesis that phosphine-induced cytotoxicity was due to decrease of ATP levels. ATP suppliers could prevent its toxicity by generating ATP through glycolysis. α-keto compounds such as dihydroxyacetone and α-ketoglutarate may bind to phosphine and restore mitochondrial respiration.

Wastewater treatment high rate algal pond biomass for bio-crude oil production.

This study investigates the production potential of bio-crude from wastewater treatment high rate algal pond (WWT HRAP) biomass in terms of yield, elemental/chemical composition and higher heating value (HHV). Hydrothermal liquefaction (HTL) of the biomass slurry (2.2wt% solid content, 19.7kJ/g HHV) was conducted at a range of temperatures (150-300°C) for one hour. The bio-crude yield and HHV varied in range of 3.1-24.9wt% and 37.5-38.9kJ/g, respectively. The bio-crudes were comprised of 71-72.4wt% carbon, 0.9-4.8wt% nitrogen, 8.7-9.8wt% hydrogen and 12-15.7wt% oxygen. GC-MS analysis indicated that pyrroles, indoles, amides and fatty acids were the most abundant bio-crude compounds. HTL of WWT HRAP biomass resulted, also, in production of 10.5-26wt% water-soluble compounds (containing up to 293mg/L ammonia), 1.0-9.3wt% gas and 44.8-85.5wt% solid residue (12.2-18.1kJ/g). The aqueous phase has a great potential to be used as an ammonia source for further algal cultivation and the solid residue could be used as a process fuel source.

Poly(ADP-ribose) polymerase-1 regulates microglia mediated decrease of endothelial tight junction integrity.

Alzheimer's disease pathology includes, beside neuronal damage, reactive gliosis and reduced blood-brain barrier (BBB) integrity. Microglia are intimately associated with the BBB and upon AD pathology, pro-inflammatory responses of microglia could contribute to BBB damage. To study whether microglia can directly affect BBB integrity, the effects of amyloid beta (Aß) -stimulated primary murine microglia on co-cultured mouse brain endothelial cells (bEnd3) and murine astrocyte cultures were assessed. We also assessed whether microglial phenotype modulation via poly(ADP-ribose) polymerase-1 (PARP-1) inhibition/ablation can reverse microglial impact on these BBB forming cells. Unstimulated microglia promoted expression of tight junction proteins (TJPs), zonula ocluden-1 (ZO-1) and occludin in co-cultured endothelia cells, whereas Aß-stimulated microglia reduced endothelial expression of ZO-1 and occludin. Astrocytes co-cultured with microglia showed elevated glial fibrillary acidic protein (GFAP) expression, which was further increased if microglia had been stimulated with Aß. Aß induced microglial release of nitric oxide (NO) and tumour necrosis factor alpha (TNFα), which resulted in reduced endothelial expression of TJPs and increased paracellular permeability. Microglial PARP-1 inhibition attenuated these Aß-induced events. These findings demonstrate that PARP-1 mediated microglial responses (NO and TNFα) can directly reduce BBB integrity by promoting TJP degradation, increasing endothelial cell permeability and inducing astrogliosis. PARP-1 as a modulator of microglial phenotype can prevent microglial BBB damaging events, and thus is a potential therapeutic target.

Biodiesel production potential of wastewater treatment high rate algal pond biomass.

This study investigates the year-round production potential and quality of biodiesel from wastewater treatment high rate algal pond (WWT HRAP) biomass and how it is affected by CO2 addition to the culture. The mean monthly pond biomass and lipid productivities varied between 2.0±0.3 and 11.1±2.5gVSS/m2/d, and between 0.5±0.1 and 2.6±1.1g/m2/d, respectively. The biomass fatty acid methyl esters were highly complex which led to produce low-quality biodiesel so that it cannot be used directly as a transportation fuel. Overall, 0.9±0.1g/m2/d (3.2±0.5ton/ha/year) low-quality biodiesel could be produced from WWT HRAP biomass which could be further increased to 1.1±0.1g/m2/d (4.0ton/ha/year) by lowering culture pH to 6-7 during warm summer months. CO2 addition, had little effect on both the biomass lipid content and profile and consequently did not change the quality of biodiesel.

Winter-time CO2 addition in high rate algal mesocosms for enhanced microalgal performance.

Carbon limitation in domestic wastewater high rate algal ponds is thought to constrain microalgal photo-physiology and productivity and CO2 augmentation is often used to overcome this limitation in summer. However, the implications of carbon limitation during winter are poorly understood. This paper investigates the effects of 0.5%, 2%, 5% and 10% CO2 addition on the winter-time performance of wastewater microalgae in high rate algal mesocosms. Performance was measured in terms of light absorption, photosynthetic efficiency, biomass production and nutrient removal rates, along with community composition. Varying percentage CO2 addition and associated change in culture pH resulted in 3 distinct microalgal communities. Light absorption by the microalgae increased by up to 144% with CO2 addition, while a reduction in the package effect meant that there was less internal self-shading thereby increasing the efficiency of light absorption. Carbon augmentation increased the maximum rate of photosynthesis by up to 172%, which led to increased microalgal biovolume by up to 181% and an increase in total organic biomass for all treatments except 10% CO2. While 10% CO2 improved light absorption and photosynthesis this did not translate to enhanced microalgal productivity. Increased microalgal productivity with CO2 addition did not result in increased dissolved nutrient (nitrogen and phosphorus) removal. This experiment demonstrated that winter-time carbon augmentation up to 5% CO2 improved microalgal light absorption and utilisation, which ultimately increased microalgal biomass and is likely to enhance total annual microalgal areal productivity in HRAPs.

Wastewater treatment high rate algal ponds (WWT HRAP) for low-cost biofuel production.

Growing energy demand and water consumption have increased concerns about energy security and efficient wastewater treatment and reuse. Wastewater treatment high rate algal ponds (WWT HRAPs) are a promising technology that could help solve these challenges concurrently where climate is favorable. WWT HRAPs have great potential for biofuel production as a by-product of WWT, since the costs of algal cultivation and harvest for biofuel production are covered by the wastewater treatment function. Generally, 800-1400 GJ/ha/year energy (average biomass energy content: 20 GJ/ton; HRAP biomass productivity: 40-70 tons/ha/year) can be produced in the form of harvestable biomass from WWT HRAP which can be used to provide community-level energy supply. In this paper the benefits of WWT HRAPs are compared with conventional mass algal culture systems. Moreover, parameters to effectively increase algal energy content and overall energy production from WWT HRAP are discussed including selection of appropriate algal biomass biofuel conversion pathways.

Study of the Effects of ATP Suppliers and Thiol Reductants on Toxicity of Pioglitazone in Isolated Rat Liver Mitochondria.

Pioglitazone (PG) is one of thiazolidinediones used for the treatment of type II diabetes mellitus. Some reports of its hepatotoxicity exist, but the mechanism of its hepatotoxicity is not well known. In the present study, the protective effect of some ATP suppliers are investigated against mitochondrial toxicity of PG in isolated rat mitochondria. Mitochondrial viability was investigated by MTT assay. The effects of PG on superoxide dismutase activity, ATP production, mitochondrial swelling and oxidative stress were also investigated. PG reduced mitochondrial viability with an LC50 of 880±32 µM. It reduced ATP production and superoxide dismutase activity in mitochondria and increased mitochondrial swelling, but no oxidant effect was present as measured by TBARS formation. Fructose, dihydroxyacetone, dithioteritol, and N-acetylcysteine reduced mitochondrial toxicity of PG. Therefore, PG toxicity may be due to its mitochondrial toxicity and energy depletion, and ATP suppliers could be effective in preventing its toxicity.

Protective effect of quercetin on oxidative stress in glucose-6-phosphate dehydrogenase-deficient erythrocytes in vitro.

Glucose-6-phosphate dehydrogenase (G6PD) deficient subjects are vulnerable to oxidative stress. Quercetin, a flavonoids, has been employed as a potent oxygen-free radical scavenger in order to assess the protective effects of quercetin against H2O2-induced oxidative damage in G6PD-deficient and normal human erythrocytes. Erythrocytes of G6PD-deficient (n = 10) and normal (n = 10) subjects were incubated with different concentrations of quercetin. The produced thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) level of erythrocytes were then subsequently measured. Different concentrations of quercetin showed no significant hemolysis, compared with the phosphate buffer solution. Upon challenge with H2O2, there was a significant (p < 0.005) decrease in GSH and an increase in TBARS level in G6PD-deficient erythrocytes. With quercetin, it managed to preserve concentrations of 15 to 75 mM preserved GSH and TBARS levels of normal and G6PD-deficient erythrocytes against H2O2-induced oxidative damage. In addition to its well-established antioxidant effects, quercetin was also found to have cytoprotective properties.