Genetic differences in the metabolism of xenobiotics have recently been suggested as modifiers of individual susceptibility to bladder cancer (BC). The objective of this study was to investigate the relationship between bladder tumor and variants of cytochrome p450 1A2 (CYP1A2) 734 C --> A, cytochrome p450 2D6 (CYP2D6) 1934 G --> A, glutathione S-transferase M1, (GSTM1 null), glutathione S-transferase T1 (GSTT1 null), and glutathione S-transferase P1 (GSTP1) I105 V. We investigated the distribution of these polymorphisms in 135 BC patients and in 128 age and sex-matched cancer-free controls. The polymorphisms were analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay and the multiplex PCR method. Genotype and allele frequencies and their associations with BC risk, demographic factors, smoking status, and tumor stage were investigated. The prevalence of GSTT1 null genotype in cases was 23%, compared with 7% in the control group (OR = 3.94, 95% CI = 1.70-9.38, P = 0.001). There was no association between the studied polymorphisms of CYP1A2, CYP2D6, GSTM1, and GSTP1 genes and BC. There was an association between smoking status and BC. These data seem to indicate that GSTT1 gene polymorphism may be associated with BC in the Turkish population studied. Further studies will be needed to clarify the role of such variation in determining susceptibility to BC.
An overdose of acetaminophen (APAP) produces centrilobular hepatocellular necrosis. We aimed to investigate the hepatoprotective effects of N-acetylcysteine (NAC) only and hyperbaric oxygen (O(2)) treatment (HBOT) combined with NAC, and their anti-inflammatory properties in liver tissue. In the current study, a total of 32 male Sprague Dawley rats were divided into 4 groups: sham, APAP, NAC, and NAC + HBOT. In the APAP, NAC, and NAC + HBOT groups, liver injury was induced by oral administration of 1 g/kg APAP. The NAC group received 100 mg/kg NAC per day. NAC + HBOT group received intraperitoneal injection of 100 mg/kg/day NAC and were given HBOT at 2.8 ATA pressure with 100% O(2) inhalation for 90 min every 12 h for 5 days. Rats in the sham group received distilled water only by gastric tube. All animals were killed on day 6 after APAP or distilled water administration. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic neopterin, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) levels were measured. There was a significant increase in serum AST and ALT activities in the APAP group compared with the sham group (in both p = 0.001). NAC and NAC + HBOT groups had significant decreases in hepatic neopterin, TNF-α, and IL-6 levels compared with the APAP group. APAP administration caused extensive hepatic necrosis. NAC and NAC + HBO treatments significantly reduced APAP-induced liver injury. Our results showed that the liver damage in APAP toxicity was attenuated by NAC and NAC + HBO treatments. NAC + HBOT exhibit hepatoprotective activity against APAP-induced liver injury in rats.
Objectives: Shock wave lithotripsy treatment (SWT) is not completely free from side effects; one of the accused mechanisms for renal injury during SWT is oxygen-and nitrogen-derived free radical productions. Therefore, we aimed to evaluate the effect of inhibition of nitric oxide (NO) production by N-[3(aminomethyl) benzyl) acetamidine] (1400W), highly selective inducible nitric oxide synthase (iNOS) inhibitor, at SWT-induced kidney damage. Materials and methods: Twenty-four rats those underwent right nephrectomy procedure were divided equally into three groups as control, SWT, and SWT + 1400W. 1400W was administered at a dose of 10 mg/kg at 2 h prior to SWT procedure and at the beginning of SWT procedure via intraperitoneal route and continued daily for consecutive 3 days. At the end of the fourth day, animals were killed via decapitation and trunk blood and the left kidneys were taken for biochemical and histopathologic evaluation. Results: SWT caused renal tubular damage and increased lipid peroxidation and antioxidant enzyme activities and SWT also significantly increased nitro-oxidative products. Inhibition of iNOS via administration of 1400W ameliorated renal injury and decreased tissue lipid peroxidation (malondialdehyde), superoxide dismutase, glutathione peroxidase and nitrite/nitrate levels (NO x ). In addition, it was seen that histolopathological changes were attenuated in the SWT + 1400W group when compared to SWT group. Conclusion: SWT-induced renal injury might be due to excessive production of oxygen free radicals and NO production. Inhibition of iNOS attenuates renal injury following SWT treatment. It can be concluded that iNOS inhibitors or peroxynitrite scavengers might be used to protect the kidneys against SWT-induced morphological and functional injuries.
Dextrose solutions (in 1%, 5%, 10%, 15%, 20% and 25% concentrations) were applied on adult human fibroblasts in vitro culture condition. Cell proliferation assay was used for finding the cell deaths in cell culture. Up to 80% fibroblast cells died in high dextrose concentrations (15%, 20% and 25%). The deaths of cells were visualized on inverted microscope. In low dextrose concentrations (1%, 5% and 10%), viable cell ratio was above 80%. The gene expression analysis were performed on selected genes which have roles on angiogenesis and apopitosis [VEGFA (Vascular Endothelial Growth Factor A-OMIM ABSTRACTObjectives: Hypertonic dextrose injection in prolotherapy is an injection-based treatment used in chronic musculoskeletal conditions. Dextrose prolotherapy raises growth factor levels and enhances tissue repair, reduces musculoskeletal pain. Despite of uses for many years, the effect of dextrose solution on cellular and molecular base is not fully clear. Here, the roles of dextrose solutions was tried to find out in different concentrations on human fibroblasts in vitro. Gene expression alterations were analyzed in uses of dextrose solutions on growth and apoptotic factors. Methods:The effects of dextrose solution (1%, 5%, 10%-low doses, 15%, 20% and 25%-high doses) were evaluated in vitro by using human fibroblast culture. In each condition total RNA extraction and cDNA synthesis were performed. The gene expression levels of angiogenic and apoptotic factors were analyzed by using real-time polymerase chain reaction. The gene expression results of growth and apoptotic factors were correlated with control results. Results:Results;Dextrose solutions were affected the viability of fibroblast cells in culture flask in high concentrations. In high doses dextrose concentrations, up to 80% of fibroblasts were died because of toxic conditions. Viable fibroblast cell ratios were decreased proportionally due to the dextrose concentration. Low dextrose concentrations increased gene expressions in angiogenic (VEGFA, PDGFA, PDGFB, IGF1) and in apopitotic factors (CASP3 and CASP8) in fibroblasts. Conclusions: Conclusion; Dextrose solution in high concentrations, decreases viable cell ratios on adult fibroblast cell line. Dextrose solutions in proper concentrations increase the gene expressions of angiagenic and apopitotic factors on viable cells in adult fibroblast cell culture.
IntroductionMultiple myeloma (MM) is a hematologic cancer characterized by uncontrolled monoclonal plasma cell proliferation (1). MM is currently an incurable B-cell malignancy that accounts for nearly 10% of human hematopoietic cancers and 1% of all human cancers (2). Presently, the 2 most effective treatment choices for patients with MM are tandem high-dose chemotherapy followed by autologous stem cell infusion, or allogeneic hematopoietic stem cell transplantation after myeloablative therapy or reduced-intensity conditioning (1). The proteasome inhibitor bortezomib is a novel drug with promising efficacy, even for patients with relapsed refractory MM (3,4). Nevertheless, these choices are not appropriate in all patients, and drug resistance often increases over time. Consequently, there is a need for new treatment options that can augment the effectiveness of current treatments (5,6).Background/aim: In this study, the in vitro and in vivo effectiveness of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE) in combination with bortezomib, a proteasome inhibitor, was explored in multiple myeloma (MM) cells. Materials and methods:The cytotoxic effects of CAPE and bortezomib were determined by XTT cell proliferation assay. Apoptosis levels were analyzed with annexin V-fluorescein isothiocyanate, nuclear factor kappa beta (NF-κB) was analyzed with electrophoretic mobility-shift assay, and interleukin (IL)-6 levels were analyzed with enzyme-linked immunosorbent assay to evaluate CAPE's mechanism of action. To investigate the in vivo effectiveness of CAPE and bortezomib, an experimental plasmacytoma model was induced in BALB/c mice.Results: Increasing concentrations of CAPE and bortezomib decreased the proliferation of ARH-77 cells in a dose-dependent manner. With doses of CAPE IC50, a significant increase in apoptosis and a significant decrease in IL-6 levels were detected. The NF-κB DNAbinding activity decreased compared to the basal ARH-77 level. The administration of CAPE alone or in combination with bortezomib increased the rate of survival compared to the control group. Conclusion:We think that our study, which is the first to demonstrate the in vitro and in vivo effectiveness of the combined use of CAPE and bortezomib, will be a pioneer for future human applications of CAPE in MM.
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