Protective effect of carnosic acid on acrylamide‐induced liver toxicity in rats: Mechanistic approach over Nrf2‐Keap1 pathway

Acrylamide is a food contaminant with a range of toxic effects. Carnosic acid (C₂₀H₂₈O₄) is a phenolic compound found in plants and has many beneficial effects. In this study, we aimed at investigating the effect of carnosic acid on acrylamide‐induced liver damage. Rats (n = 7) were allotted to control, carnosic acid, acrylamide, acrylamide + carnosic acid groups. Animals were euthanized. Their blood was taken for biochemical analysis, and liver tissue was excised for morphological, immunohistochemical, and immunoblotting analyses. As a result, acrylamide reduced bodyweight, liver weight, catalase, and total antioxidant capacity levels but increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total oxidant status, oxidative stress index levels, Nrf2, and Keap1 protein levels. In addition, acrylamide disrupted liver histology leading to vascular congestion, cellular infiltration, necrotic cells, and so forth. Carnosic acid cotreatment ameliorated the altered biochemical parameters, liver histology, Nrf2, and Keap1 enzyme levels. In conclusion, carnosic acid has the potential to be used as a protective agent against acrylamide‐induced liver damage.     

Effect of drought stress implemented at pre- or post-anthesis stage on some physiological parameters as screening criteria in chickpea cultivars

Drought is one of the most important factors limiting chickpea production in arid and semi-arid regions. There is little information regarding genotypic variation for drought tolerance in chickpea cultivars. Screening for drought tolerance is very important. It is essential to identify the physiological mechanisms of drought tolerance to complete conventional breeding program. Glasshouse experiment was carried out to study the genotypic variation among 11 chickpea (Cicer arietinum L.) cultivars. Plants were grown either under optimum conditions or drought stress was implemented at pre-or post-anthesis stages. The drought susceptibility index (DSI) was used as the measure of drought tolerance. Relationships between DSI and excised-leaf water loss (RWL), relative water content (RWC), membrane permeability, ascorbic acid, proline, and chlorophyll contents, lipid peroxidation, and hydrogen peroxide concentrations were determined in order to find out whether these physiological parameters could be used as the genotypic selection criteria for drought tolerance. The results of this study indicated that there was a wide variation in tolerance to drought stress among the chickpea cultivars, which could be exploited in breeding new chickpea cultivars with high drought tolerance. The results also demonstrated that drought-tolerant cultivars had a higher RWC, ascorbic acid and proline concentrations, but lower RWL and membrane permeability in comparison to drought-sensitive cultivars. The significant and a well defined relationships between DSI and RWC, RWL, ascorbic acid, proline, and membrane permeability were found. It was concluded that these parameters could be instrumental in predicting the drought tolerance of chickpea cultivars. This text was submitted by the authors in English.     

Atypical heterochromatin organization and replication are rapidly acquired by somatic cells following fusion-mediated reprogramming by mouse ESCs

We recently reported that mouse embryonic stem cells (ESCs) in S/G₂ are more efficient at reprogramming somatic cells than ESCs at other stages of the cell cycle. We also provided evidence that DNA replication is induced in the nuclei of somatic partners upon fusion with ESC partners, and showed that this was critical for their conversion toward a pluripotent state.¹ Here we have used counterflow centrifugal elutriation to enrich for ESCs at different cell cycle phases, so as to examine in detail the properties of S/G₂ phase cells. This revealed that the replication and organization of DAPI-intense heterochromatin in ESCs is unusual in two respects. First, replication of heterochromatin occurred earlier during S phase and was associated with precocious H3S10 phosphorylation. Second, heterochromatin protein 1 α (HP1α), which invariably marks DAPI-intense and H3K9me3-enriched pericentromeric domains in mouse somatic cells,² was not necessarily associated with these H3K9me3-enriched domains in undifferentiated ESCs. These data, which complement recent replication timing³ and electron spectroscopic imaging (ESI) analyses,⁴ suggest that heterochromatin is atypical in ESCs. Interestingly, as these unusual features were rapidly acquired by somatic nuclei upon ESC fusion-mediated reprogramming, our results suggest that fundamental changes in cell cycle structure and heterochromatin dynamics may be important for conferring pluripotency.     

Valproic acid inhibits the proliferation of SHSY5Y neuroblastoma cancer cells by downregulating URG4/URGCP and CCND1 gene expression

Valproic acid (VPA), used for the treatment of epilepsy and bipolar disorder, regulates several signaling pathways in brain cells. The up-regulated gene 4 (URG4/URGCP) is a novel gene located on 7p13. URG4/URGCP stimulates cyclin D1 (CCND1) mRNA expression, and URG4/URGCP silencing diminishes CCND1 mRNA expression in HepG2 cells. This study was performed to investigate the anti-cancer mechanism of action of VPA by analyzing the expression of novel gene URG4/URGCP, CCND1, p21, p53, p65 (RelA), Bax, and Bcl-2 in SHSY5Y neuroblastoma (NB) cancer cells. Cytotoxic effects of VPA in SHSY5Y were noticed in time and dose dependent manner with the IC₅₀ doses within the range of 0.5–10 mM. IC₅₀ doses in the SHSY5Y were detected as 7.5 mM. Expression profiles were determined by semi quantitative RT-PCR and URG4/URGCP protein change by western blot analysis. Our results suggest that VPA induces cell cycle arrest in SHSY5Y due to the decrease in URG4/URGCP, CCND1 gene expression and the increase in p65. To conclude, VPA may be a prospective agent for the treatment of NB as a single agent or in combination with other drugs. Thus, more studies should be designed to find a safe dose with the best effects of VPA.     

Silicon-mediated changes of some physiological and enzymatic parameters symptomatic for oxidative stress in spinach and tomato grown in sodic-B toxic soil

We investigated effect of silicon (Si) on the growth, uptake of sodium (Na), chloride (Cl), boron (B), stomatal resistance (SR), lipid peroxidation (MDA), membrane permeability (MP), lipoxygenase (LOX) activity, proline (PRO) accumulation, H₂O₂ accumulation, non-enzymatic antioxidant activity (AA) and the activities of major antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT and ascorbate peroxidase, APX) of spinach and tomato grown in sodic-B toxic soil. Si applied to the sodic-B toxic soil at 2.5 and 5.0 mM concentrations significantly increased the Si concentration in the plant species and counteracted the deleterious effects of high concentrations of Na, Cl and B on root and shoot growth by lowering the accumulation of these elements in the plants. Stomatal resistance, MP, MDA and the concentrations of H₂O₂ and PRO were higher in the plants grown in sodic-B toxic soil without Si: LOX activity of excised leaves of both species was increased by Si. Antioxidant activities of both species were significantly affected by Si, with the activities of SOD, CAT and APX decreased and AA increased by applied Si. For most of the parameters measured, it was found that 5 mM Si was more effective than the 2.5 mM Si. Based on the present work, it can be concluded that Si alleviates sodicity and B toxicity of the plants grown in sodic-B toxic soil by preventing both oxidative membrane damage and also translocation of Na, Cl and B from root to shoots and/or soil to plant, and lowering the phytotoxic effects of Na, Cl and B within plant tissues. It was concluded that tomato was more responsive to Si than spinach since it was more salt sensitive than spinach. To our knowledge, this is the first report that Si improves the combined salt and B tolerance of spinach and tomato grown in naturally sodic-B toxic soil, and which describes membrane-related parameters and antioxidant responses.     

The Effects of Inhaled <Emphasis Type="Italic">Pimpinella peregrina</Emphasis> Essential Oil on Scopolamine-Induced Memory Impairment,Anxiety, and Depression in Laboratory Rats

In the present study, we identified the effects of inhaled Pimpinella peregrina essential oil (1 and 3 %, for 21 continuous days) on scopolamine-induced memory impairment, anxiety, and depression in laboratory rats. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by means of the elevated plus-maze and forced swimming tests. The scopolamine alone-treated rats exhibited the following: decrease of the spontaneous alternation percentage in Y-maze test, increase of the number of working and reference memory errors in radial arm-maze test, along with decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. Inhalation of the P. peregrina essential oil significantly improved memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. Our results suggest that the P. peregrina essential oil inhalation ameliorates scopolamine-induced memory impairment, anxiety, and depression. Moreover, studies on the P. peregrina essential oil may open a new therapeutic window for the prevention of neurological abnormalities closely related to Alzheimer’s disease.     

Computational insights on the competing effects of nitric oxide in regulating apoptosis

Despite the establishment of the important role of nitric oxide (NO) on apoptosis, a molecular-level understanding of the origin of its dichotomous pro- and anti-apoptotic effects has been elusive. We propose a new mathematical model for simulating the effects of nitric oxide (NO) on apoptosis. The new model integrates mitochondria-dependent apoptotic pathways with NO-related reactions, to gain insights into the regulatory effect of the reactive NO species N(2)O(3), non-heme iron nitrosyl species (FeL(n)NO), and peroxynitrite (ONOO(-)). The biochemical pathways of apoptosis coupled with NO-related reactions are described by ordinary differential equations using mass-action kinetics. In the absence of NO, the model predicts either cell survival or apoptosis (a bistable behavior) with shifts in the onset time of apoptotic response depending on the strength of extracellular stimuli. Computations demonstrate that the relative concentrations of anti- and pro-apoptotic reactive NO species, and their interplay with glutathione, determine the net anti- or pro-apoptotic effects at long time points. Interestingly, transient effects on apoptosis are also observed in these simulations, the duration of which may reach up to hours, despite the eventual convergence to an anti-apoptotic state. Our computations point to the importance of precise timing of NO production and external stimulation in determining the eventual pro- or anti-apoptotic role of NO.     

Essential oil composition of two endemic Centaurea species from Turkey, Centaurea mucronifera and Centaurea chrysantha, collected in the same habitat

The essential oils of two endemic Centaurea species from Turkey, C. mucronifera and C. chrysantha, collected in the same habitat, have been studied. The main compounds of the former were germacrene D (29.3%), β-eudesmol (17.4%) and β-caryophyllene (7.3%), while in the latter germacrene D (27.4%), caryophyllene oxide (9.5%) and bicyclogermacrene (5.4%) were detected among its major constituents. The two species produced many similar compounds in their essential oils that could be justified by the similar ecological conditions of their habitat, but also many differences were found that could confirm their taxonomic separation.