Hyperthermia and Controllable Free Radical Coenhanced Synergistic Therapy in Hypoxia Enabled by Near-Infrared-II Light Irradiation.

Tumor cell metabolism and tumor blood vessel proliferation are distinct from normal cells. The resulting tumor microenvironment presents a characteristic of hypoxia, which greatly limits the generation of oxygen free radicals and affects the therapeutic effect of photodynamic therapy. Here, we developed an oxygen-independent free radical generated nanosystem (CuFeSe2-AIPH@BSA) with dual-peak absorption in both near-infrared (NIR) regions and utilized it for imaging-guided synergistic treatment. The special absorption provides the nanosystem with high photothermal conversion efficiency and favorably matched photoactivity in both I and II NIR biological windows. Upon NIR light irradiation, the generated heat could prompt AIPH release and decompose to produce oxygen-independent free radicals for killing cancer cells effectively. The contrastive research results show that the enhanced therapeutic efficacy of NIR-II over NIR-I is principally due to its deeper tissue penetration and higher maximum permission exposure that benefits from a longer wavelength. Hyperthermia effect and the production of toxic free radicals upon NIR-II laser illumination are extremely effective in triggering apoptosis and death of cancer cells in the tumor hypoxia microenvironment. The high biocompatibility and excellent anticancer efficiency of CuFeSe2-AIPH@BSA allow it to be an ideal oxygen-independent nanosystem for imaging-guided and NIR-II-mediated synergistic therapy via systemic administration.

New Strategies for the Delivery of Some Natural Anti-oxidants with Therapeutic Properties.

Nature offers tremendous potential in the medicine field. Natural antioxidant molecules inhibit or quench free radical reactions and delay or inhibit cellular damage. In the last few years, researchers have been focusing on the health benefits of natural products. Particularly some dietary nutrients, such as curcumin, crocin, resveratrol, quercetin, coenzyme Q10, vitamin C, as well as some polysaccharides have been evaluated for their numerous and unique therapeutic properties. This review focuses on examples of pharmaceutical applications of natural anti-oxidants, with special regards to their encapsulation in micro- and nano- delivery systems. In vitro and in vivo studies have been conducted to investigate the physicochemical and pharmacological properties of different delivery systems containing antioxidant molecules. For instance, ethosomes, organogels, monoolein aqueous dispersions and solid lipid nanoparticle have been considered. It was found that micro and nanoencapsulation strategy can improve the solubility of lipophilic molecules and the chemical stability of labile antioxidants, thus prolonging their efficacy. In vitro and in vivo studies have highlighted that antioxidant encapsulation prolongs release kinetics, bioavailability and antioxidant effects. Noticeably, some encapsulated antioxidants effectively inhibit cancer cell proliferation, cell migration and colony formation, thus suppressing cancer progression.

Alterations of hepatocyte function with free radical generators and reparation or prevention with coffee polyphenols.

Liver diseases are linked in the majority of cases to oxidative stress that antioxidants could neutralize with reducing liver injury. Chlorogenic acid, a coffee polyphenol, possesses antioxidant prosperities. The aim of this study was to evaluate in vitro preventive and corrective effects of cholorogenic acid in hepatocyte toxicity induced by free radicals. Hepatocytes were isolated from adult male Wistar rats. To determine corrective effects and reparation, cells were first exposed to two free radical generators (hydrogen peroxide/iron sulfate for hydroxyl radical formation, and phenazine methosulfate/nicotinamide adenine dinucleotide for superoxide anion formation) for 12H and thereafter treated by chlorogenic acid (1 and 10 µM final concentration) for another 12H. To show preventive effects, cells were pretreated by chlorogenic acid and thereafter exposed to free radical generators. Hepatocyte proliferation, glucose uptake, ATP contents, membrane fluidity and integrity, and intracellular redox status were investigated after 24H culture. The results showed that chlorogenic acid reversed the decrease in cell proliferation, glucose uptake and ATP levels, the increased LDH release and the reduced membrane fluidity and restored the oxidant/antioxidant status under oxidative stress. When pre-treated with chlorogenic acid, hepatocytes became very resistant to oxidative conditions and cellular homeostasis was maintained. In conclusion, chlorogenic acid displayed not only corrective but also preventive effects in hepatocytes exposed to oxidative stress and could be beneficial in patients with or at risk of liver diseases.

Antioxidants and cataract.

The major causes for cataract formation are free radicals, and these free radicals are neutralized by the presence of endogenous antioxidants in the eye. Using xenobiotics, it has been confirmed that free radicals mediate the formation of cataract. Two cataract model-selenite model and the diabetic cataract model-have been developed to study the pathophysiology of cataract formation due to free radicals and the role of antioxidants during the process of cataractogenesis. This review focuses on natural compounds with antioxidant properties that could actually be applied as an interventional strategy on a large scale and are also relatively inexpensive. A brief overview of plants with antioxidant properties that in addition possess potential anti-cataract properties has been discussed. In addition to plants, three natural compounds (curcumin, vitamin C and vitamin E), on which a lot of data exist showing anti-cataract and antioxidant activities, have also been discussed. These antioxidants can be supplemented in the diet for a better defence against free radicals. Studies on vitamin C and vitamin E have proved that they are capable of preventing lipid peroxidation, thereby preventing the generation of free radicals, but their efficacy as anti-cataract agent is questionable. Unlike vitamins C and E, curcumin is well established as an anti-cataract agent, but the issue of curcumin bioavailability is yet to be addressed. Nanotechnology proves to be a promising area in increasing the curcumin bioavailability, but still a lot more research needs to be done before the use of curcumin as an effective anti-cataract agent for humans.

L-cysteine supplementation lowers blood glucose, glycated hemoglobin, CRP, MCP-1, and oxidative stress and inhibits NF-kappaB activation in the livers of Zucker diabetic rats.

This study examined the hypothesis that l-cysteine supplementation can lower insulin resistance, glycemia, oxidative stress, and markers of vascular inflammation in type 2 diabetes using Zucker diabetic fatty (ZDF) rats as a model. Starting at the age of 6 weeks, ZDF rats were supplemented orally (daily gavage, 8 weeks) with saline placebo (D) or l-cysteine (LC; 1 mg/kg bw) and fed a high-calorie diet. Six-week-old rats without any supplementation were considered baseline (BL) rats. D rats showed elevated fasting blood glucose, glycated Hb, CRP, and MCP-1 compared with BL rats in which there was no onset of diabetes. LC supplementation significantly lowered blood levels of glucose (18%, p= 0.05), glycated Hb (8%, p= 0.02), CRP (23%, p= 0.02), MCP-1 (32%, p= 0.01), and insulin resistance (25%) compared with levels seen in saline-supplemented D rats. There was a decrease in plasma protein oxidation levels (p< 0.01); however, GSH levels were similar in LC and D groups. Although LC did not change blood hematocrit or levels of transaminases, it did lower alkaline phosphatase (29%, p= 0.01) levels in comparison to D. Western blotting analyses of liver showed increased activation of NF-kappaB and Akt (50% pNF-kappaB and 20% pAkt) in D compared with BL rats. LC supplementation inhibited these effects (17% pAkt, 18% pNF-kappaB). This is the first report showing that l-cysteine supplementation can lower glycemia and markers of vascular inflammation in diabetes apparently by preventing NF-kappaB activation in a diabetic animal model.

Efectos del extracto de té verde sobre los daños oxidativos inducidos por cisplatino en riñones y testículos de ratas / Effect of green tea extract on cisplatin induced oxidative damage on kidney and testes of rats

Se administró extracto de té verde (Camellia sinensis) por vía oral a las ratas en dosis de 25, 50 y 100 mg/kg para investigar sus efectos sobre la nefrotoxicidad y la toxicidad testicular inducida por cisplatino (3mg/kg). El extracto de té verde restauró el nivel de creatinina, urea, nitrógeno ureico en sangre (NUS) y ácido úrico en el suero de animales tratados con cisplatino en comparación con los animales tratados sólo con cisplatino. Además, se observó que la administración de extracto de té verde restauró los niveles de enzimas antioxidantes como superóxido dismutasa (SOD), catalasa (CAT) y glutatión reducido (GSH), y enzimas ligadas a la membrana como Na Na+K+ATPasa, Ca Ca2+ 2+ ATPasa y Mg Mg2+ 2+ ATPasa y redujo la peroxidación lipídica (MDA) en los riñones y en los testículos de animales con alteraciones tras el tratamiento crónico con cisplatino. Por tanto, se puede concluir que el extracto de té verde posee actividad antioxidante y que, en virtud de esta acción, puede proteger los riñones y los testículos frente a los daños oxidativos inducidos por el cisplatino

Green tea extract (Camellia sinensis) was administered orally to rats at the dose levels of 25, 50,100 mg/kg to investigate its effect on cisplatin (3mg/kg) induced nephrotoxicity and testicular toxicity. Green tea extract restored the level of creatinine, urea, blood urea nitrogen (BUN) and uric acid in serum of animals treated with cisplatin as compared to the animals treated with cisplatin alone. It was further found that administration of green tea extract restored the level of antioxidant enzymes such as, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), and membrane bound enzymes like Na Na+K+ ATPase, Ca Ca2+ 2+ ATPase and Mg Mg2+ 2+ ATPase and decreased lipid peroxidation (MDA) in kidney and in testes of animals which were altered after chronic treatment with cisplatin. Thus it can be concluded that green tea extract possesses antioxidant activity and by virtue of this action it can protect the kidney and testes from cisplatin induced oxidative damage

Antioxidant effects of 1,5-anhydro-D-fructose, a new natural sugar, in vitro.

The antioxidant effects of 1,5-anhydro-D-fructose (1,5-AF), a unique anhydrohexulose, were studied in 1,1-diphenyl-2-picrylhydrazyl (DPPH) solution, in human cells along with lipid peroxidation of low-density lipoprotein (LDL). We have confirmed that 1,5-AF scavenges DPPH radicals directly in solution and inhibits the formation of hydrogen peroxide and superoxide anion, typical reactive oxygen species (ROS), induced by phorbol myristate acetate (PMA) in a dose-dependent manner in THP-1 cells. We also observed the dose-dependent antioxidant effects of 1,5-AF on copper-mediated LDL oxidation. These findings suggest that 1,5-AF might play a role in reducing the risk of atherosclerosis and may help prevent coronary heart disease.