Protection against oxidative stress in hepatic and pancreatic cells by selected plant-derived chemicals

Persistent accumulation of free radicals in cells leads to oxidative stress, which plays a causative role in the induction and progression of various chronic diseases. Therapeutic focus has therefore shifted towards the use of antioxidants, with recent interest in those of plant origin. This study investigated radical scavenging and cytoprotective activities of phytochemicals (quercetin, curcumin, sulforaphane, rosmarinic acid, caffeic acid, danshensu (3,4-dihydroxyphenyllactic acid), ferulic acid and m-coumaric acid) against DPPH free radical in a non-cellular assay, and oxidative damage in hepatic (HepG2) and pancreatic (1.1B4) cells, elicited by an organic hydroperoxide (tert-butylhydroperoxide - tBHP) and a more physiologically relevant stressor (palmitate). Direct and indirect cytoprotective activities were assessed by neutral red viability assay after 5 h co-exposure and 20 h pre-exposure conditions, respectively. Radical scavenging activities of three well-known phytochemicals - quercetin, curcumin and sulforaphane - were initially validated against DPPH (non-cellular assay), where quercetin was shown to be more potent than curcumin; sulforaphane was without effect. With quercetin as positive control, radical scavenging activities of rosmarinic acid and three of its principal metabolites (caffeic acid, danshensu and ferulic acid) were comparable, while m-coumaric acid lacked antiradical activity against DPPH radical. Subsequently in HepG2 hepatoma cells, quercetin and curcumin were confirmed to possess direct and indirect cytoprotective acitivities against 0.5 mM tBHP while, sulforaphane only had indirect cytoprotective acitivities. Additionally, co-treatment of HepG2 cells with low concentrations of quercetin and curcumin (used together) exhibited direct cytoprotective activities against tBHP. However, direct cytoprotective potencies of rosmarinic acid and caffeic acid were less than quercetin. Similar pattern was observed for indirect cytoprotective activities; with danshensu, ferulic acid and m-coumaric acid lacking hepatoprotective activity in co-exposure and pre-exposure conditions. These results highlight the discrepancy between non-cellular and cellular antioxidant activities, which could be accounted to the poor lipophilicity profiles of rosmarinic acid and its principal metabolites. Cytotoxicity assay in 1.1B4 human pancreatic β-cells revealed that these cells were more vulnerable to tBHP-induced oxidative damage than HepG2 cells. An investigation of selected phytochemicals in 1.1B4 cells produced novel findings, with quercetin exhibiting direct and indirect cytoprotective activities against tBHP (0.125 mM and 0.5 mM). Curcumin and caffeic acid were also cytoprotective against 0.125mM tBHP but only exhibited direct cytoprotection against 0.5mM tBHP. Sulforaphane lacked both direct and indirect cytoprotective activities in 1.1B4 cells, exhibiting marked cytotoxic effects in both conditions. Further analysis in both HepG2 and 1.1B4 cells proved that indirect cytoprotective activities of selected phytochemicals were not dependent on pro-proliferative activities of quercetin, curcumin, caffeic acid and sulforaphane. Moreover, it was observed that high concentrations of curcumin and sulforaphane caused necrosis in both cell types, rather than apoptosis; caffeic acid also produced necrotic effect in 1.1B4 cells. Whilst prolonged exposure of HepG2 and 1.1B4 cells to high glucose concentrations failed to elicit any evidence of glucotoxicity, sodium palmitate caused concentration-dependent cytotoxicity after short-term (5 h) and long-term (20 h) exposure to both cell types. Overall, selected phytochemicals caused additive cytotoxicity in the presence of palmitate, although quercetin demonstrated direct cytoprotection alone in HepG2 cells. Using Western blot, curcumin, caffeic acid and sulforaphane did not upregulate NQO1, but 20 h exposure to 0.1 mM quercetin resulted in upregulation in HepG2 cells, amidst high basal levels of NQO1 in this cell type. However, both basal and inductive expression of NQO1 has not been observed in 1.1B4 cells. Thus, although rosmarinic acid, danshensu, caffeic acid and ferulic acid may possess good intrinsic antioxidant properties, their physicochemical properties may limit pharmacological activities at the cellular level. Moreover, the additive cytotoxicity resulting from treatment with selected phytochemicals and sodium palmitate highlights a discrepancy between mechanisms of cytotoxicities by tBHP and palmitate

Police views of suicidal persons and the law criminalizing attempted suicide in Ghana: A qualitative study with policy implications

The penal code of Ghana condemns suicide attempt. The present study sought to explore the views of the police on persons who attempt suicide and the law criminalizing the act. Qualitative in-depth interviews were used to explore the views of 18 officers of the Ghana Police Service. Data were analyzed using thematic analysis technique. Findings showed that the police officers profiled suicide attempters as needy, enigmatic, ignorant, and blameworthy. Majority (n = 14) of them disagreed with the law and suggested a repeal, whereas only four of them agreed with the law. Regardless of their positions on criminalization, they showed an inclination to help, rather than arrest, when confronted with such persons in line of their duty. Educating the police on suicidal behavior may help to deepen their understanding and help improve the way they handle suicidal persons. This may also strengthen police suicide prevention gatekeeping obligations

Protection against oxidative stress in hepatic and pancreatic cells by selected plant-derived chemicals

Persistent accumulation of free radicals in cells leads to oxidative stress, which plays a causative role in the induction and progression of various chronic diseases. Therapeutic focus has therefore shifted towards the use of antioxidants, with recent interest in those of plant origin. This study investigated radical scavenging and cytoprotective activities of phytochemicals (quercetin, curcumin, sulforaphane, rosmarinic acid, caffeic acid, danshensu (3,4-dihydroxyphenyllactic acid), ferulic acid and m-coumaric acid) against DPPH free radical in a non-cellular assay, and oxidative damage in hepatic (HepG2) and pancreatic (1.1B4) cells, elicited by an organic hydroperoxide (tert-butylhydroperoxide - tBHP) and a more physiologically relevant stressor (palmitate). Direct and indirect cytoprotective activities were assessed by neutral red viability assay after 5 h co-exposure and 20 h pre-exposure conditions, respectively. Radical scavenging activities of three well-known phytochemicals - quercetin, curcumin and sulforaphane - were initially validated against DPPH (non-cellular assay), where quercetin was shown to be more potent than curcumin; sulforaphane was without effect. With quercetin as positive control, radical scavenging activities of rosmarinic acid and three of its principal metabolites (caffeic acid, danshensu and ferulic acid) were comparable, while m-coumaric acid lacked antiradical activity against DPPH radical. Subsequently in HepG2 hepatoma cells, quercetin and curcumin were confirmed to possess direct and indirect cytoprotective acitivities against 0.5 mM tBHP while, sulforaphane only had indirect cytoprotective acitivities. Additionally, co-treatment of HepG2 cells with low concentrations of quercetin and curcumin (used together) exhibited direct cytoprotective activities against tBHP. However, direct cytoprotective potencies of rosmarinic acid and caffeic acid were less than quercetin. Similar pattern was observed for indirect cytoprotective activities; with danshensu, ferulic acid and m-coumaric acid lacking hepatoprotective activity in co-exposure and pre-exposure conditions. These results highlight the discrepancy between non-cellular and cellular antioxidant activities, which could be accounted to the poor lipophilicity profiles of rosmarinic acid and its principal metabolites. Cytotoxicity assay in 1.1B4 human pancreatic β-cells revealed that these cells were more vulnerable to tBHP-induced oxidative damage than HepG2 cells. An investigation of selected phytochemicals in 1.1B4 cells produced novel findings, with quercetin exhibiting direct and indirect cytoprotective activities against tBHP (0.125 mM and 0.5 mM). Curcumin and caffeic acid were also cytoprotective against 0.125mM tBHP but only exhibited direct cytoprotection against 0.5mM tBHP. Sulforaphane lacked both direct and indirect cytoprotective activities in 1.1B4 cells, exhibiting marked cytotoxic effects in both conditions. Further analysis in both HepG2 and 1.1B4 cells proved that indirect cytoprotective activities of selected phytochemicals were not dependent on pro-proliferative activities of quercetin, curcumin, caffeic acid and sulforaphane. Moreover, it was observed that high concentrations of curcumin and sulforaphane caused necrosis in both cell types, rather than apoptosis; caffeic acid also produced necrotic effect in 1.1B4 cells. Whilst prolonged exposure of HepG2 and 1.1B4 cells to high glucose concentrations failed to elicit any evidence of glucotoxicity, sodium palmitate caused concentration-dependent cytotoxicity after short-term (5 h) and long-term (20 h) exposure to both cell types. Overall, selected phytochemicals caused additive cytotoxicity in the presence of palmitate, although quercetin demonstrated direct cytoprotection alone in HepG2 cells. Using Western blot, curcumin, caffeic acid and sulforaphane did not upregulate NQO1, but 20 h exposure to 0.1 mM quercetin resulted in upregulation in HepG2 cells, amidst high basal levels of NQO1 in this cell type. However, both basal and inductive expression of NQO1 has not been observed in 1.1B4 cells. Thus, although rosmarinic acid, danshensu, caffeic acid and ferulic acid may possess good intrinsic antioxidant properties, their physicochemical properties may limit pharmacological activities at the cellular level. Moreover, the additive cytotoxicity resulting from treatment with selected phytochemicals and sodium palmitate highlights a discrepancy between mechanisms of cytotoxicities by tBHP and palmitate

Reactions of some Confectionery Groundnut Accessions to Plant Parasitic Nematodes Infection

Investigations were conducted at four locations in Ghana during 2011 growing season to evaluate some confectionery groundnut accessions reactions to plant parasitic nematodes infection. Sixteen groundnut accessions were evaluated at Fumesua, Wenchi, Ejura and Atebubu in a 4 x 4 lattice design with three replications. Seeds were sown in four-row plots, five metres long at spacing of 50 cm between and 20 cm within rows. Plant parasitic nematodes populations per 200 cm3 soil, days of groundnut to 50% anthesis, days to maturity, pods/plant and pod yield were analyzed using GenStat statistical package. Three accessions; ICGV97040, ICGV97051 and ICGV97058 significantly (P < 0.05) reduced nematodes populations by (92, 94 and 79%), (92, 89 and 97%) and (86, 79 and 100%) in Meloidogyne arenaria, Pratylenchus brachyurus and Aphelenchoides arachidis compared with ICGV97045, ICGV97047 and ICGV97049 respectively at Wenchi. ICGV97051 which yielded the highest (3.2 t/ha) was approximately 97% higher than ICGV97061 (0.1 t/ha) the lowest yielding accession. ICGV97051 was identified as the most promising accession on account of high yielding and nematode suppression potential.Keywords: Aphelenchoides arachidis, Arachis hypogaea, Meloidogyne arenaria, Pratylenchus brachyurus, Rotylenchulus reniformis, Scutellonema bradys

Three specific gut bacteria in the occurrence and development of colorectal cancer: a concerted effort

Colorectal cancer (CRC), which develops from the gradual evolution of tubular adenomas and serrated polyps in the colon and rectum, has a poor prognosis and a high mortality rate. In addition to genetics, lifestyle, and chronic diseases, intestinal integrity and microbiota (which facilitate digestion, metabolism, and immune regulation) could promote CRC development. For example, enterotoxigenic Bacteroides fragilis, genotoxic Escherichia coli (pks+ E. coli), and Fusobacterium nucleatum, members of the intestinal microbiota, are highly correlated in CRC. This review describes the roles and mechanisms of these three bacteria in CRC development. Their interaction during CRC initiation and progression has also been proposed. Our view is that in the precancerous stage of colorectal cancer, ETBF causes inflammation, leading to potential changes in intestinal ecology that may provide the basic conditions for pks+ E. coli colonization and induction of oncogenic mutations, when cancerous intestinal epithelial cells can further recruit F. nucleatum to colonise the lesion site and F. nucleatum may contribute to CRC advancement by primarily the development of cancer cells, stemization, and proliferation, which could create new and tailored preventive, screening and therapeutic interventions. However, there is the most dominant microbiota in each stage of CRC development, not neglecting the possibility that two or even all three bacteria could be engaged at any stage of the disease. The relationship between the associated gut microbiota and CRC development may provide important information for therapeutic strategies to assess the potential use of the associated gut microbiota in CRC studies, antibiotic therapy, and prevention strategies

Inhibition of human carbonyl reducing enzymes by plant anthrone and anthraquinone derivatives

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Critical Role of Monooxygenase in Biodegradation of 2,4,6-Trinitrotoluene by <i>Buttiauxella</i> sp. S19-1

2,4,6-Trinitrotoluene (TNT) is an aromatic pollutant that is difficult to be degraded in the natural environment. The screening of efficient degrading bacteria for bioremediation of TNT has received much attention from scholars. In this paper, transcriptome analysis of the efficient degrading bacterium Buttiauxella sp. S19-1 revealed that the monooxygenase gene (BuMO) was significantly up-regulated during TNT degradation. S-ΔMO (absence of BuMO gene in S19-1 mutant) degraded TNT 1.66-fold less efficiently than strain S19-1 (from 71.2% to 42.9%), and E-MO mutant (Escherichia coli BuMO-expressing strain) increased the efficiency of TNT degradation 1.33-fold (from 52.1% to 69.5%) for 9 h at 180 rpm at 27 °C in LB medium with 1.4 µg·mL−1 TNT. We predicted the structure of BuMO and purified recombinant BuMO (rBuMO). Its specific activity was 1.81 µmol·min−1·mg−1 protein at pH 7.5 and 35 °C. The results of gas chromatography mass spectrometry (GC–MS) analysis indicated that 4-amino-2,6-dinitrotoluene (ADNT) is a metabolite of TNT biodegradation. We speculate that MO is involved in catalysis in the bacterial degradation pathway of TNT in TNT-polluted environment

Integral use of Argentinean Solanum betaceum red fruits as functional food ingredient to prevent metabolic syndrome: effect of in vitro simulated gastroduodenal digestion

The “red chilto” (Solanum betaceum Cav) is a native fruit from the Yungas forest of Argentina. Red chilto is a neglected and underutilized native species (NUS). The objective of this work was to evaluate the potentiality of pulp, seed and skin from “red chilto” as a functional food ingredient to add value to a native resource of Argentine Yungas to promote sustainable integral use of it. The powders have low carbohydrate and sodium content and are a source of vitamin C, phenolic acids (rosmarinic acid and caffeoylquinic acid), anthocyanins, condensed tannins, carotenoids, potassium, and fiber. The phenolics of chilto powders showed, before and after simulated gastroduodenal digestion, antioxidant activity (ABTS•+; H2O2; O2 •; HO•) and were able to inhibit enzymes related to metabolic syndrome, such as α-glucosidase, α-amylase and lipase. Chilto powder showed hypoglycemic effect by increasing glucose adsorption, decreasing glucose diffusion rate and by promoting glucose transport across the cell membrane. These results suggest the potential of Argentinean “red chilto” fruits as functional food ingredients or dietary supplements to prevent metabolic syndrome principally by its antioxidant, hypoglycemic and hypolipemic effects.Fil: Orqueda, Maria Eugenia. Universidad Nacional de Tucumán. Instituto de Bioprospección y Fisiología Vegetal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Bioprospección y Fisiología Vegetal; ArgentinaFil: Torres, Sebastián. Universidad Nacional de Tucumán. Instituto de Bioprospección y Fisiología Vegetal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Bioprospección y Fisiología Vegetal; Argentina. Universidad Nacional de Tucumán; ArgentinaFil: Zampini, Iris Catiana. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Universidad Nacional de Tucumán. Instituto de Bioprospección y Fisiología Vegetal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Bioprospección y Fisiología Vegetal; ArgentinaFil: Cattaneo, Florencia. Universidad Nacional de Tucumán. Instituto de Bioprospección y Fisiología Vegetal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Bioprospección y Fisiología Vegetal; ArgentinaFil: Fernández Di Pardo, Agustina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Valle, Estela Marta. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Jiménez Aspee, Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Schmeda Hirschmann, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Isla, Maria Ines. Universidad de Talca; Chile. Universidad Nacional de Tucumán. Instituto de Bioprospección y Fisiología Vegetal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Bioprospección y Fisiología Vegetal; Argentin