Intraoperative thermal mapping of mammary tumors in dogs.

In this study, videothermometry's application in detecting mammary tumors in dogs is explored in-depth. The research hypothesizes that this technique can effectively identify cancerous tissues during surgery by analyzing thermal patterns. The methodology involved comparing thermal imaging results from dogs with palpable mammary nodules against a control group, focusing on capturing real-time thermal patterns. Results were significant, showing distinct thermal patterns in carcinomas. This indicates videothermometry's capability in accurately identifying micro metastases and differentiating between neoplastic and non-neoplastic changes. The study concludes that videothermometry has considerable potential in enhancing surgical precision, especially in tumor resection and safety margin definition, but emphasizes the need for further research to thoroughly understand the thermal signatures of various mammary tumors in dogs.

Effects of redox modulation on quiescin/sulfhydryl oxidase activity of melanoma cells.

Secreted quiescin/sulfhydryl oxidase (QSOX) is overexpressed in many tumor cell lines, including melanoma, and is usually associated with a pro-invasive phenotype. Our previous work described that B16-F10 cells enter in a quiescent state as a protective mechanism against damage generated by reactive oxygen species (ROS) during melanogenesis stimulation. Our present results show that QSOX activity was two-fold higher in cells with stimulated melanogenesis when compared to control cells. Considering that glutathione (GSH) is one of the main factor responsible for controlling redox homeostasis in cells, this work also aimed to investigate the relationship between QSOX activity, GSH levels and melanogenesis stimulation in B16-F10 murine melanoma cell line. The redox homeostasis was impaired by treating cells with GSH in excess or depleting its intracellular levels through BSO treatment. Interestingly, GSH-depleted cells without stimulation of melanogenesis kept high levels of viability, suggesting a possible adaptive mechanism of survival even under low GSH levels. They also showed lower extracellular activity of QSOX, and higher QSOX intracellular immunostaining, suggesting that this enzyme was less excreted from cells and corroborating with a diminished extracellular QSOX activity. On the other hand, cells under melanogenesis stimulation showed a lower GSH/GSSG ratio (8:1) in comparison with control (non-stimulated) cells (20:1), indicating a pro-oxidative state after stimulation. This was accompanied by decreased cell viability after GSH-depletion, no alterations in QSOX extracellular activity, but higher QSOX nucleic immunostaining. We suggest that melanogenesis stimulation and redox impairment caused by GSH-depletion enhanced the oxidative stress in these cells, contributing to additional alterations of its metabolic adaptive response.

The metabolic response of Araucaria angustifolia embryogenic cells to heat stress is associated with their maturation potential.

Araucaria angustifolia is a critically endangered species and its distribution can be affected by an increase in temperature. In this study, we evaluated the effects of heat stress (30°C) on Araucaria angustifolia cell lines responsive (SE1) and non-responsive (SE6) to the development of somatic embryos. The viability of both cell lines was reduced by heat stress and mitochondria were the organelles most affected. Heat stress for 24h increased the reactive oxygen species (ROS) levels in SE1 cells, followed by a reduction at 48 and 72h. In SE6 cells, an increase occurred after 24 and 48h of stress, returning to control levels at 72h. H2 O2 levels were increased after 24h for both SE1 and SE6 cells, being higher for SE6. Interestingly, at 48 and 72h, H2 O2 levels decreased in SE1 cells, while in SE6, the values returned to the control levels. The respiration of SE6 cells in the presence of oxidisable substrates was inhibited by heat stress, in agreement with the high lipid peroxidation levels. The AaSERK1 gene was identified in both cultures, with greater expression in the SE1 line. Heat stress for 24 and 48h increased gene expression only in this cell line. The activity of peroxidase, superoxide dismutase and enzymes of the glutathione/ascorbate cycle was increased in both cell lines subjected to heat stress. Catalase activity was increased only in SE6 cells at 72h of exposure. These results show that responsive SE1 cells can modulate ROS levels more efficiently than SE6 when these cells are stressed by heat. This ability may be related to the maturation capacity of these cells.

Influence of red wine polysaccharides on cytochrome P450 enzymes and inflammatory parameters in tumor models.

The soluble fraction of polysaccharides from cabernet franc red wine (SFP) previously showed antitumoral effects by modulating the immune system. The present study tested the hypothesis that the SFP can regulate CYPs in vitro in HepG2 cells and in vivo in Walker-256 tumor-bearing rats. The SFP was used in the following protocols: (i) solid tumor, (ii) liquid tumor, and (iii) chemopreventive solid tumor. The SFP reduced solid tumor growth in both solid tumor protocols but did not inhibit liquid tumor development. The SFP reduced total CYP levels in the solid and liquid tumor protocols and reduced the gene expression of Cyp1a1 and Cyp2e1 in rats and CYP1A2 in HepG2 cells. An increase of N-acetylglucosaminidase activity was observed in all SFP-treated rats, and TNF-α levels increased in the solid tumor protocol in the vehicle, SFP, and vincristine (positive control) groups. The chemopreventive solid tumor protocol did not modify CYP levels in the liver or intestine or N-acetylglucosaminidase and myeloperoxidase activity in the liver. The in vitro digestion and nuclear magnetic resonance analyses suggested that SFP was minimally modified in the gastrointestinal system. In conclusion, SFP inhibited CYPs both in vivo and in vitro, likely as a result of its immunoinflammatory actions.

Use of sildenafil and L-arginine in an experimental rat model for the prevention of neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) has a 45% mortality in neonatal intensive care units. This paper aimed to evaluate the isolated and combined effects of sildenafil and L-arginine in the prevention of necrotizing enterocolitis. Neonatal rats were fed formula milk and submitted to hypoxia under a 100% N2 atmosphere for 70 s. Then, animals were subjected to hypothermia (4 °C for 10 min), twice a day for 3 days. Forty neonatal rats were divided into five groups: negative control-not submitted to the protocol (n = 5), sildenafil group-NEC protocol (n = 9), L-arginine group-NEC protocol (n = 9), L-arginine and sildenafil group-NEC protocol (n = 9) and positive control-NEC protocol and intraperitoneal saline solution (n = 8). Jejunum and terminal ileus were removed for histopathologic and immunohistochemical Ki-67 analysis. Kruskal-Wallis test was used to analyze mortality, survival, body weight, intestinal injury score and Ki-67 proliferation index. All animals submitted to the protocol developed enterocolitis. Mortality rate was higher in group that received only L-arginine (p = 0.0293). The Ki-67 analysis showed a higher proliferative index in groups that received interventional drugs (p = 0.017). In conclusion, sildenafil and L-arginine were not effective to reduce intestinal injury.

The mesoionic compound MI-D changes energy metabolism and induces apoptosis in T98G glioma cells.

The mesoionic compound 4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride (MI-D) impairs mitochondrial oxidative phosphorylation and has a significant antitumour effect against hepatocarcinoma and melanoma. This study evaluated the cytotoxic effect of MI-D on T98G glioblastoma cells and investigated whether the impairment of oxidative phosphorylation promoted by MI-D is relevant to its cytotoxic effect. The effects of MI-D on T98G cells cultured in high glucose Dulbecco's modified Eagle's medium (DMEM) HG (glycolysis-dependent) and galactose plus glutamine-supplemented Dulbecco's modified Eagle's medium (DMEM) GAL (oxidative phosphorylation-dependent) were compared. T98G cells grown in DMEM GAL medium exhibited higher respiration rates and citrate synthase activity and lower lactate levels, confirming the metabolic shift to oxidative phosphorylation in these cells. MI-D significantly decreased the cell viability in a dose-dependent manner in both media; however, T98G cells cultured in DMEM GAL medium were more susceptible. The mesoionic significantly inhibited mitochondrial oxidative phosphorylation of glioma cells in both media. At the same time, lactate levels were not altered, indicating an absence of compensatory glycolysis activation. Additionally, MI-D increased the citrate synthase activity of cells in both media, which in DMEM HG-cultivated cells was followed by citrate accumulation. Apoptosis dependent on caspase-3 mediated the toxicity of MI-D on T98G cells. The higher susceptibility of glioma cells cultured in DMEM GAL medium to MI-D indicates that the impairment of mitochondrial functions is involved in mesoionic cytotoxicity. The results of this study indicate the potential use of MI-D for glioblastoma treatment.

The toxicity of 1,3,4-thiadiazolium mesoionic derivatives on hepatocarcinoma cells (HepG2) is associated with mitochondrial dysfunction.

Mesoionic compounds, 4-phenyl-5-(4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivatives (MI-J: X = OH; MI-D: X = NO2), possess significant antitumor and cytotoxic effects on several cancer cells. In this work, we evaluated the cytotoxicity of MI-J and MI-D on human hepatocellular carcinoma (HepG2 cells) grown in either high glucose (HG) or galactose medium (GAL) to clarify whether the effects of mesoionics on mitochondrial bioenergetics are associated with their cytotoxicity in these cells. MI-J and MI-D (5-50 µM) decreased the viability of HepG2 cells in a dose- and time-dependent manner, as assessed by MTT, LDH release and dye with crystal violet assays. Both compounds at lower (5 µM) and intermediate (25 µM) concentrations were more toxic to cells grown in GAL medium. MI-J inhibited the basal state of respiration in HepG2 cells cultured in HG and GAL media; however, in GAL medium, this effect occurred at the lowest concentration (5 µM). A leak-state stimulus was observed only after incubation with MI-J (5 µM) for GAL medium. MI-D stimulated and inhibited the leak state in cells grown in HG medium at concentrations of 5 µM and 25 µM, respectively. In cells cultured in GAL medium, respiration was strongly inhibited by MI-D at the highest concentration (25 µM). In contrast, at 5 µM, the mesoionic inhibited the basal and uncoupled states at 30% and 50%, respectively. The inhibition of the basal state by MI-J and MI-D was consistent with the increase in lactate levels in both media, which was higher for the GAL medium. Both mesoionics slightly decreased pyruvate levels only in cells cultured in GAL medium. Additionally, MI-J (25 µM) reduced the ATP amount in cells cultured in both media, while MI-D (25 µM) promoted a reduction only in cells grown in GAL medium. Our results show that MI-J and MI-D depress mitochondrial respiration and consequently change metabolism and reduce ATP levels, effects associated with their toxicity in hepatocarcinoma cells.

Cytotoxic effect of xyloglucan and oxovanadium (IV/V) xyloglucan complex in HepG2 cells.

It is well known that the chemical structure of polysaccharides is important to their final biological effect. In this study we investigated the cytotoxic effect of xyloglucan from Copaifera langsdorffii seeds (XGC) and its complex with oxovanadium (XGC:VO) on hepatocellular carcinoma cells (HepG2). After 72 h of incubation, XGC and XGC:VO (200 µg/mL) reduced cell viability in ~20% and ~40%, respectively. At same conditions, only XGC:VO increased in ~20% the LDH enzyme release. In permeabilized cells, incubated with XGC and XGC:VO (200 µg/mL) for 72 h, NADH oxidase activity was reduced by ~45% with XGC and XGC:VO. The succinate oxidase activity was reduced by ~35% with XGC and ~65% with XGC:VO, evidencing that polysaccharide complexation with vanadium could intensify its effects on the respiratory chain. According to this result, the mitochondrial membrane potential was also reduced by ~9% for XGC and ~30% for XGC:VO, when compared to the control group. Interestingly, ATP levels were more elevated for XGC:VO in respect to XGC, probably due the enhance in glycolytic flux evidenced by increased levels of lactate. These results show that the xyloglucan complexation with oxovanadium (IV/V) potentiates the cytotoxic effect of the native polysaccharide, possibly by impairment of oxidative phosphorylation.

Mitochondrial bioenergetics and enzymatic antioxidant defense differ in Paraná pine cell lines with contrasting embryogenic potential.

Araucaria angustifolia is classified as a critically endangered species by the International Union for Conservation of Nature. This threat is worsened by the inefficiency of methods for ex-situ conservation and propagation. In conifers, somatic embryogenesis (SE) associated with cryopreservation is an efficient method to achieve germplasm conservation and mass clonal propagation. However, the efficiency of SE is highly dependent on genotype responsivity to the artificial stimulus used in vitro during cell line proliferation and later during somatic embryo development. In this study, we evaluated the activity of antioxidant enzymes and characterized mitochondrial functions during the proliferation of embryogenic cells of A. angustifolia responsive (SE1) and non-responsive (SE6) to the development of somatic embryos. The activities of the antioxidant enzymes GR (EC 1.6.4.2), MDHAR (EC 1.6.5.4), and POX (EC 1.11.1.7) were increased in SE1 culture, while in SE6 culture, only the activity of DHAR (EC 1.8.5.1) was significantly higher. Additionally, SE6 culture presented a higher number of mitochondria, which agreed with the increased rate of oxygen consumption compared to responsive SE1 culture; however, the mitochondrial volume was lower. Although the ATP levels did not differ, the NAD(P)H levels were higher in SE1 cells. NDs, AOX, and UCP were less active in responsive SE1 than in non-responsive cells. Our results show significant differences between SE1 and SE6 embryogenic cells regarding mitochondrial functions and antioxidant enzyme activities, which may be intrinsic to the in vitro proliferation phase of both cell lines, possessing a crucial role for the induction of in vitro maturation process.

Antineoplastic activity of a novel ruthenium complex against human hepatocellular carcinoma (HepG2) and human cervical adenocarcinoma (HeLa) cells.

Novel metal complexes have received much attention recently because of their potential anticancer activity. Notably, ruthenium-based complexes have emerged as good alternatives to the currently used platinum-based drugs for cancer therapy, with less toxicity and fewer side effects. The beneficial properties of Ru, which make it a highly promising therapeutic agent, include its variable oxidative states, low toxicity, and high selectivity for cancer cells. The present study evaluated the cytotoxic effects of a ruthenium complex, namely cis-[Ru(1,10-phenanthroline)2(imidazole)2]2+ (RuC), on human hepatocellular carcinoma (HepG2) and human cervical adenocarcinoma (HeLa) cells and analyzed metabolic parameters. RuC reduced HepG2 and HeLa cell viability at all tested concentrations (10, 50, and 100 nmol/L) at 48 h of incubation, based on the MTT, Crystal violet, and neutral red assays. The proliferation capacity of HepG2 cells did not recover, whereas HeLa cell proliferation partially recovered after RuC treatment. RuC also inhibited all states of cell respiration and increased the levels of the metabolites pyruvate and lactate in both cell lines. The cytotoxicity of RuC was higher than cisplatin (positive control) in both lineages. These results indicate that RuC affects metabolic functions that are related to the energy provision and viability of HepG2 and HeLa cells and is a promising candidate for further investigations that utilize models of human cervical adenocarcinoma and mainly hepatocellular carcinoma.

Hypoxia protects against the cell death triggered by oxovanadium-galactomannan complexes in HepG2 cells.

BACKGROUND: Polysaccharides from various sources have been used in traditional medicine for centuries. The beneficial pharmacological effects of plant-derived polysaccharides include anti-tumor activity. METHODS: Here, we evaluated the anti-cancer effect of the MSAGM:VO complex under hypoxic conditions (1% oxygen). MSAGM:VO is a complex of the hydrolysate of galactomannan (MSAGM) from Schizolobium amazonicum with oxovanadium (IV/V). The hepatocellular carcinoma (HCC) cell line HepG2 was selected as HCC are one of the most hypoxic solid tumors. RESULTS: Our results showed that the strong apoptotic activity of MSAGM:VO observed in HepG2 cells under normoxic conditions was completely lost under hypoxic conditions. We found a dynamic balance between the pro- and anti-apoptotic members of the Bcl-2 protein family. The expressions of anti-apoptotic Mcl-1 and Bcl-XL increased in hypoxia, whereas the expression of pro-apoptotic Bax decreased. MSAGM:VO strongly induced autophagy, which was previously characterized as a pro-survival mechanism in hypoxia. These results demonstrate total elimination of the anti-cancer activity of MSAGM:VO with activation of autophagy under conditions of hypoxia. CONCLUSION: Although this study is a proof-of-concept of the impact of hypoxia on the potential of polysaccharides, further study is encouraged. The anti-tumor activity of polysaccharides could be achieved in normoxia or through raising the activity of the immune system. In addition, combination strategies for therapy with anti-autophagic drugs could be proposed.

Cytotoxicity of xyloglucan from Copaifera langsdorffii and its complex with oxovanadium (IV/V) on B16F10 cells.

The aim of this study was to investigate the effects of xyloglucan extracted from Copaifera langsdorffii seeds (XGC) and its complex with oxovanadium (XGC:VO) in murine melanoma B16F10 cells. The formation of complexes was followed by potentiometric titration and further demonstrated by 51V RMN. The viability and proliferation of B16F10 cells were reduced up 50% by the xyloglucan and its complex, both at 200 µg/mL, from 24 to 72 h. Cytotoxic effects of XGC and XGC:VO do not involve changes in cell cycle progression. Only XGC:VO (200 µg/mL) promoted the cell death evidenced by annexin V stain. XGC increased the respiration and lactate levels in melanoma cells, while XGC:VO reduced about 50% the respiration and levels of pyruvate, without alter the lactate levels, indicating that both xyloglucan preparations interfere with the metabolism of B16F10 cells. No change in activity of the enzyme hexokinase and expression of pyruvate kinase M2 was observed. XGC:VO (200 µg/mL) negatively modulated the expression of the ß subunit of ATP synthase. The results demonstrate that the cytotoxicity of XGC and XGC:VO on murine melanoma B16F10 cells can be related to the impairment of the mitochondrial functions linked to energy provision.

Effects of silymarin on angiogenesis and oxidative stress in streptozotocin-induced diabetes in mice.

The present study evaluated the effects of acute treatment with silymarin, an extract that is obtained from Silybum marianum, on angiogenesis, oxidative stress, and inflammation in normoglycemic and diabetic mice. Diabetes was induced by streptozotocin (80 mg/kg, intraperitoneal) in male Swiss mice, 6 weeks of age. A polyether-polyurethane sponge was surgically implanted in the back of the mice as a model of healing in both diabetic and normoglycemic animals that were treated with oral silymarin or water for 10 days. The pancreas, liver, kidneys, blood, and sponges were collected and analyzed. Diabetes led to impairments of antioxidant defenses, reflected by a reduction of pancreatic superoxide dismutase and hepatic and renal catalase and an increase in pancreatic lipoperoxidation. An inflammatory process was observed in diabetic mice, reflected by an increase in pancreatic tumor necrosis factor α (TNF-α) and the infiltration of inflammatory cells in islets. The number of vessels was lower in the implanted sponges in diabetic mice. Silymarin treatment attenuated this damage, restoring antioxidant enzymes and reducing pancreatic TNF-α and inflammatory infiltration. However, silymarin treatment did not restore angiogenesis or glycemia. In conclusion, treatment with silymarin red uced oxidative stress and inflammation that were induced in the model of streptozotocin-induced diabetes in several organs, without apparent toxicity. Silymarin may be a promising drug for controlling diabetic complications.

Effects of a new antiprotozoal drug, N,N'-diphenyl-4-methoxy-benzamidine, on energy-linked functions of rat liver mitochondria.

Amidines are chemically characterized by the presence of two nitrogen atoms that bind to the same carbon atom in its structure. Several biological activities have been ascribed to these compounds. Pentamidine, an aromatic diamidine, is effective in the treatment against Pneumocystis carinii and leishmaniasis, but it can also have severe side effects. New amidine derivatives have been synthesized, among them N,N'-diphenyl-4-methoxy-benzamidine (methoxyamidine), which is effective against Leishmania amazonensis (LD50 = 20 µM) and Trypanosoma cruzi (LD50 = 59 nM). In the present study, methoxyamidine toxicity was evaluated in isolated rat liver mitochondria at the same range of concentrations that exert antiprotozoal activity. In these organelles, actively oxidizing glutamate + malate inhibited state 3 respiration (25 nmol mg-1 of protein) by ∼15%. The sites of inhibition in the respiratory chain were complex I and the segment between ubiquinone and complex III. Methoxyamidine also stimulated state 4 respiration by ∼32% and ∼43% at 50 and 65 nmol mg-1 of protein, respectively. Its uncoupling effect was confirmed by a dose-dependent increase in oxygen consumption in state 4 respiration that was induced by oligomycin, reaching up to ∼69% (65 nmol mg-1 of protein) and an increase in ATPase activity in intact mitochondria by ∼27% and ∼83% at 50 and 65 nmol mg-1 protein, respectively. Swelling that was supported by the oxidation of glutamate + malate in the presence of sodium acetate was reduced by methoxyamidine by ∼16% and 32% at 50 and 65 nmol mg-1 protein, respectively. Mitochondrial swelling in the absence of substrate and in the presence of K+ and valinomycin was inhibited by ∼20% at the same concentrations, suggesting that methoxyamidine affects mitochondrial membrane permeability and fluidity. Our data show that methoxyamidine has slight effects on the energy-linked functions of isolated mitochondria at concentrations that correspond to the LD50 against Leishmania amazonensis and Trypanosoma cruzi. These findings may prompt further studies that evaluate methoxyamidine toxicity in vivo.

Toxicity of native and oxovanadium (IV/V) galactomannan complexes on HepG2 cells is related to impairment of mitochondrial functions.

Polysaccharides and vanadium compounds have been studied due to their antitumor potential. In this study, the cytotoxic effects of galactomannan preparations on HepG2 cells were investigated. Native galactomannan from S. amazonicum (SAGM) and its modified form (MSAGM) were complexed with oxovanadium resulting in SAGM:VO and MSAGM:VO, respectively. The complexation was confirmed by NMR, FTIR, and AAS. SAGM and MSAGM:VO (250µg/mL) after 72h decreased viability by 51% and 58%, respectively, while the inhibition of the HepG2 cell proliferation was of ∼27% and ∼46%, respectively. SAGM and MSAGM:VO (250µg/mL) significantly inhibited all states of respiration (basal: 85% and 63%; uncoupled: 90% and 70%; and leak: 30% and 58%) after 72h. ROS levels increased by ∼149% after the treatment with MSAGM:VO (250µg/mL) for 72h, while ΔΨm decreased by ∼50%. Our results indicate that galactomannan preparations from S. amazonicum, especially SAGM and the MSAGM:VO complex, could be considered as potential antitumor drugs for further investigations, once they have the ability to make HepG2 cells susceptible to death by affecting vital cellular processes such as respiration and ROS generation.

Ruthenium complex exerts antineoplastic effects that are mediated by oxidative stress without inducing toxicity in Walker-256 tumor-bearing rats.

The present study evaluated the in vivo antitumor effects and toxicity of a new Ru(II) compound, cis-(Ru[phen]2[ImH]2)2+ (also called RuphenImH [RuC]), against Walker-256 carcinosarcoma in rats. After subcutaneous inoculation of Walker-256 cells in the right pelvic limb, male Wistar rats received 5 or 10mgkg-1 RuC orally or intraperitoneally (i.p.) every 3 days for 13 days. A positive control group (2mgkg-1 cisplatin) and negative control group (vehicle) were also used. Tumor progression was checked daily. After treatment, tumor weight, plasma biochemistry, hematology, oxidative stress, histology, and tumor cell respiration were evaluated. RuC was effective against tumors when administered i.p. but not orally. The highest i.p. dose of RuC (10mgkg-1) significantly reduced tumor volume and weight, induced oxidative stress in tumor tissue, reduced the respiration of tumor cells, and induced necrosis but did not induce apoptosis in the tumor. No clinical signs of toxicity or death were observed in tumor-bearing or healthy rats that were treated with RuC. These results suggest that RuC has antitumor activity through the modulation of oxidative stress and impairment of oxidative phosphorylation, thus promoting Walker-256 cell death without causing systemic toxicity. These effects make RuC a promising anticancer drug for clinical evaluation.

Cytotoxic effect of a mannogalactoglucan extracted from Agaricus bisporus on HepG2 cells.

A mannogalactoglucan (RK2-Ab; Mw 1.8×104gmol-1) composed by Man (27.3%), Gal (24.4%) and Glc (48.3%) was extracted and characterized from Agaricus bisporus, and its biological activity was evaluated on human hepatocarcinoma cells (HepG2). The partially-O-methylated alditol acetates together with the NMR data suggest the main chain to be composed of α-d-Galp (32.8%) and ß-d-Glcp (37.0%) units (1→6)-linked, with ß-d-Manp (14.6%), as non-reducing end units, substituting the side chains at O-2 (α-d-Galp units; 3.3%) and O-2 and O-4 (ß-d-Glcp units; 3.6%). (1→2)-linked ß-d-Glcp (2.7%) and ß-d-Manp (6.0%) can also be observed. RK2-Ab reduced cellular viability of HepG2 cells, by both, the MTT and lactate dehydrogenase release assays, promoted the increase of cytochrome c release and decrease of ATP content. Suggesting that the mannogalactoglucan from A. bisporus may have antitumor activity by inducing apoptosis by the mitochondrial death pathway, and could be used in cancer therapy.

Galactomannan from Schizolobium amazonicum seed and its sulfated derivatives impair metabolism in HepG2 cells.

This study evaluated the effects of native galactomannan from Schizolobium amazonicum seeds and its sulfated forms on certain metabolic parameters of HepG2 cells. Aqueous extraction from S. amazonicum seeds furnished galactomannan with 3.2:1 Man:Gal ratio (SAGM) and molar mass of 4.34×105g/mol. The SAGM fraction was subjected to sulfation using chlorosulfonic acid to obtain SAGMS1 and SAGMS2 with DS of 0.4 and 0.6, respectively. Cytotoxicity of SAGM, SAGMS1, and SAGMS2 was evaluated in human hepatocellular carcinoma cells (HepG2). After 72h, SAGM decreased the viability of HepG2 cells by 50% at 250µg/mL, while SAGMS1 reduced it by 30% at the same concentration. SAGM, SAGMS1, and SAGMS2 promoted a reduction in oxygen consumption and an increase in lactate production in non-permeabilized HepG2 cells after 72h of treatment. These results suggest that SAGM, SAGMS1, and SAGMS2 could be recognized by HepG2 cells and might trigger alterations that impair its survival. These effects could be implicated in the modification of the oxidative phosphorylation process in HepG2 cells and activation of the glycolytic pathway.

Polyphenol-Rich Foods Alleviate Pain and Ameliorate Quality of Life in Fibromyalgic Women.

Objectives: The present study aimed to describe the antioxidant dietary intake of patients with fibromyalgia and explore the association of the results with glutathione status, pain, quality of life, and socioeconomic status. METHODS: 38 fibromyalgic female patients and 35 female controls (mean age = 48.6 ± 8.1 and 47.6 ± 10.0 years, respectively) were evaluated. The number of tender points, pain threshold, quality of life, physical activity, socioeconomic status, nutritional status, intake of antioxidant micronutrients and foods with high total antioxidant capacity, and total salivary glutathione were evaluated. RESULTS: The number of tender points, pain threshold, and quality of life were worse in the fibromyalgia group. The consumption of vegetable juices was more common among women with fibromyalgia and consumption of red wine and beer were more common among healthy women. The adjusted mean intakes of antioxidant vitamins as well as selenium were higher for the control group (p ≤ 0.01). There was no difference for salivary levels of glutathione between the groups and no correlation for intake of antioxidant micronutrients and pain or quality of life among fibromyalgic women. However, intake of foods rich in polyphenols was associated with lower numbers of tender points (coffee, r = - 0.346; pear, r = - 0.331) and better quality of life (red fruits, r = - 0.342; dark chocolate, r = - 0.404) in the fibromyalgic group. In these women, associations between glutathione levels and food intake, pain or quality of life were not found. CONCLUSION: This study indicated that antioxidant protection from bioactive compounds present in fruit and vegetables could have an adjuvant role in fibromyalgia treatment.