RESUMO
Hypoxia can cause significant changes in the glucose metabolism of cancer cells that prefer aerobic glycolysis for energy production instead of the conventional oxidative phosphorylation mechanism. In this study, breast cancer cells (MCF-7) were exposed to glucose (0-5.5-15-55 mM), during specific incubation periods (3, 6, 12, or 24 hours) under normoxic and hypoxic conditions. The expression levels of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and glycolytic enzymes at varying glucose concentrations in cells were investigated in the different oxygen environments. It was determined that glycolytic enzymes [Hexokinase 2 (HK2), Pyruvate Kinase M2 (PKM2), Glucose-6-phosphate dehydrogenase (G6PD), Lactate Dehydrogenase A (LDHA), Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH), and Phosphofructokinase M (PFKM)] increased at the transcriptional level, especially in the first hours. This increase indicates that major metabolic reprogramming in response to hypoxia probably occurs over a short period of time. The increase in G6PD gene expression under high glucose and hypoxia conditions suggests that the pentose phosphate pathway (PPP) is used by cancer cells to synthesize necessary precursors for the cell. The results of the study showed that there is a significant interaction between hypoxia and glycolytic metabolism in cancer cells. It is thought that metabolic pathways activated by hypoxia and related genes located in these pathways will contribute to the literature by offering the potential to be target molecules for therapeutic purposes.
RESUMO
The increase in the rate of inflammation in the post-menopause period also leads to a significant increase in the use of anti-inflammatory agents. This study aimed to investigate the effect of BA supplementation on pro-and anti-inflammatory cytokines in ovariectomy (OVX) induced rats. A total of 48 nonpregnant female Wistar albino rats (80-100 g) were used in the experiment. Forty-eight rats were divided into six equal groups (n=8): Control, OVX, OVX+5 mg/kg BA (OVX+BA5), OVX+10 mg/kg BA (OVX+BA10), 5 mg/kg BA (BA5), 10 mg/kg BA (BA10). Serum TNF-α cytokine levels of rats in the OVX group were higher than in control rats (P<0.05). TNF-α levels were significantly reduced in the OVX-induced rats with 5 mg/kg BA and 10 mg/kg BA supplementation (P<0.05). While serum IL-1α and IL-6 levels were not different between OVX and control rats, serum IL-3 levels were low (P<0.05) and not affected by 5 mg/kg and 10 mg/kg BA supplementation. Serum IL-11 levels increased significantly in the OVX rats with 5 mg/kg and 10 mg/kg BA supplementation (P<0.05). As far as we know, certain doses (5 and 10 mg/kg) of BA are the first study on the prevention of increased inflammation in rats induced by OVX. Results suggest that the supplementation of BA regulates the inflammatory changes associated with OVX and thus has beneficial for menopause management.
Assuntos
Citocinas , Fator de Necrose Tumoral alfa , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácidos Bóricos , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Ovariectomia/efeitos adversos , Ratos , Ratos WistarRESUMO
Biotransformation enzymes are stimulated or inhibited depending on the exposure to xenobiotics and widely used as a biomarker. In this study, EROD activity, GST activity, reduced GSH amount, amount of lipid peroxidation product MDA as oxidative stress parameter, and ACHE inhibition as a neuromuscular parameter were measured in liver and muscle tissues of rainbow trout (Oncorhynchus mykiss) produced in aquaculture of Kemer Dam and in concrete ponds located in Fethiye. Samples were collected in January and July from fish farming in net cages in Kemer Dam and concrete cages in Fethiye in order to evaluate seasonal changes. Also, physicochemical properties of water samples collected from trout farms were measured and evaluated together with five biomarkers. Significant ACHE inhibition was observed in both stations in parallel with the increase in ammonium nitrogen in the July period (p ≤ 0.05). In parallel with the increase in turbidity in the Kemer Dam, a significant increase in GSH, MDA level, and GST activity was detected (p ≤ 0.05). As a result of the assessment of all data, significant increases were detected in EROD induction, GST activity, MDA level, and ACHE inhibition in concrete cages in Fethiye when compared to Kemer Dam (p ≤ 0,05). It was observed that pollution was at a lower level in July compared to January, and in Kemer Dam compared to Fethiye.
Assuntos
Monitoramento Ambiental , Oncorhynchus mykiss , Animais , Aquicultura , Biomarcadores , FígadoRESUMO
Hypoxia plays an important role in tumor phenotype and progression and alters glycolysis, with changes in signaling pathways that develop in response to hypoxia. In this study, the effects of oxygen (normoxia/hypoxia) and of glucose levels on the glucose metabolism was investigated in MCF-7 cancer cells. Under either normoxia or hypoxia conditions, the cells were exposed to glucose at different concentrations (0, 5.5, 15 or 55 mM) for either 3, 6, 12, 24 or 48 h. In all groups, cell viability, levels of key enzymes reflecting glycolytic metabolism in cell lysates, glucose consumed in the medium and extracellular lactate levels and wound closure percentages were determined. In hypoxic cells, intracellular consumption of glucose, and extracellular lactate levels due to increased glucose concentration were observed to be higher (compared to normoxia) and as a result of prolonged exposure to hypoxia, cells were observed to develop resistance to the prolonged exposure to hypoxia. The number of glycolytic enzymes obtained at different levels proved that cells had different potential capacities and changing mechanisms for the metabolic needs of the cell depending on the glucose amount in the medium and time in adapting to the oxygen tension. This study showed that there was an important interaction between hypoxia and glucose metabolism in general, and it was concluded that metabolic processes activated by hypoxia could offer new therapeutic targets.
RESUMO
The present study aimed at detecting DNA damage and fragmentation as well as histone acetylation depending on oxidative stress caused by CCl4 intoxication. Also, the protective role of N-acetyl cysteine, a precursor for GSH, in DNA damage is investigated. Sixty rats were used in this study. In order to induce liver toxicity, CCl4 in was dissolved in olive oil (1/1) and injected intraperitoneally as a single dose (2 ml/kg). N-acetyl cysteine application (intraperitoneal, 50 mg/kg/day) was started 3 days prior to CCl4 injection and continued during the experimental period. Control groups were given olive oil and N-acetyl cysteine. After 6 and 72 h of CCl4 injection, blood and liver tissue were taken under ether anesthesia. Nuclear extracts were prepared from liver. Changes in serum AST and ALT activities as well as MDA, TAS, and TOS levels showed that CCl4 caused lipid peroxidation and liver damage. However, lipid peroxidation and liver damage were reduced in the N-acetyl cysteine group. Increased levels in 8-hydroxy-2-deoxy guanosine and histone acetyltransferase activities, decreased histone deacetylase activities, and DNA breakage detected in nuclear extracts showed that CCl4 intoxication induces oxidative stress and apoptosis in rat liver. The results of the present study indicate that N-acetyl cysteine has a protective effect on CCl4-induced DNA damage.
Assuntos
Acetilcisteína/metabolismo , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dano ao DNA , Acetilação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Histona Acetiltransferases/metabolismo , Histona Desacetilases/metabolismo , Histonas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The purpose of this study was to evaluate the acute phase protein (serum amyloid A, C-reactive protein, haptoglobin, ceruloplasmin and fibrinogen) profiles in pregnant dogs as well as bitches at various stages of the estrus cycle and to verify possible relationship(s) among the APPs profile and hormonal status. A total of 60 bitches of various breeds were enrolled. The animals were divided into six groups. B-mode ultrasonographic scanner (concept M/C) was used for pregnancy diagnosis, involving the first and second halves of pregnancy. Proestrus, estrus, diestrus and anestrus stages of sexual cycles were differentiated by use of vaginal cytology and blood progesterone and estradiol 17-beta levels. Serum C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin, ceruloplasmin and fibrinogen levels were determined. No statistically significant differences were observed between the groups with regard to the serum SAA and CRP concentrations. Haptoglobin, ceruloplasmin and fibrinogen concentrations were elevated in pregnant dogs compared to non-pregnant groups', independently from the pregnancy stage. No statistically significant differences in acute phase protein concentrations in dogs at various stages of estrus could be detected. Results of this study indicated that ceruloplasmin and fibrinogen levels may have potential importance in the diagnosis of pregnancy, and acute phase proteins may be used for monitoring the health status of the pregnant dogs.
Assuntos
Proteínas de Fase Aguda/metabolismo , Estro/fisiologia , Prenhez/metabolismo , Animais , Proteína C-Reativa/metabolismo , Ceruloplasmina/metabolismo , Cães , Feminino , Fibrinogênio/metabolismo , Haptoglobinas/metabolismo , Gravidez , Proteína Amiloide A Sérica/metabolismoRESUMO
The aim of this study was to determine the zinc, iron, copper, calcium, phosphorus, and magnesium levels in blood serum and zinc and copper levels in hair of dogs with canine visceral leishmaniasis. The serum zinc and iron levels were found to be significantly lower in diseased dogs than those of healthy controls. Serum copper levels were significantly higher, whereas no significant differences were observed for calcium, phosphorus, and magnesium. There were no significant differences in the zinc and copper levels in hair. Our results show that the serum zinc, iron, and copper levels are altered in canine leishmaniasis.