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ABSTRACT: Effects of Cu(2+), Ni(2+) or Cu(2+) + Ni(2+) on lipid peroxide and glutathione (GSH) levels in U937 cells were investigated. Cells were treated with 0, 5, 10, and 20 µM of Cu(2+) and/or Ni(2+) and H(2)O(2) (0.01 mM) and incubated for 24 hours at 37°C. Lipid peroxides were measured by the thiobarbituric acid assay (TBA). GSH intracellular levels were assayed by the GSH assay kit from EMD/Calbiochem (San Diego, California, USA). Cu(2+) or Ni(2+) significantly (P < 0.01) increased lipid peroxides in a dose-dependent manner, compared to controls. The effect was more pronounced for Cu(2+), compared to the Ni(2+)-treated samples. Cu(2+) + Ni(2+) increased lipid peroxides in a significant (P < 0.001), dose-dependent manner, compared to Cu(2+) or Ni(2+) alone (i.e., ratio of 2.5:1-fold for combined versus single treatments, respectively). Cu(2+) or Ni(2+) significantly decreased GSH levels in U937 cells, with the effect being pronounced for Cu(2+). Cu(2+) + Ni(2+) metal ions significantly (P < 0.001) depleted cells of GSH in a dose-dependent manner. Ethylene diamine tetraacetic acid (EDTA) at 50 or 100 µM moderately reduced the Cu(2+)- or Ni(2+)-induced effects on GSH levels. Interestingly, GSH levels generally decreased to half (except for the combined metal dose of 20 µM at 100 µM EDTA) of its level at the highest metal concentration tested for both the single or combined treatments. In conclusion, multiple exposures of cells to metal ions may be lethal to cells, compared to their single treatments.
Drug and Chemical Toxicology 05/2012; · 1.08 Impact Factor
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ABSTRACT: BackgroundColorectal cancer (CRC), the most lethal long-term complication of inflammatory bowel disease (IBD), is the culmination of
a complex sequence of molecular and histologic derangements of the colon epithelium that are initiated and at least partially
sustained by prolonged chronic inflammation. Dysplasia, the earliest histologic manifestation of this process, plays an important
role in cancer prevention by providing the first clinical alert that this sequence is under way and by serving as an endpoint
in colonoscopic surveillance of patients at high risk for CRC. Restorative proctocolectomy (RPC) is indicated for patients
with IBD, specifically for ulcerative colitis that is refractory to medical treatment, emergency conditions, and/or in case
of neoplastic transformation. Even after RPC with mucosectomy, pouch-related carcinomas have recently been reported with increasing
frequency since the first report in 1984. We review IBD-associated CRC and pouch-related neoplasia prevalence, adverse events,
risk factors, and surveillances.
MethodsLiterature of IBD-associated CRC patients and those undergoing RPC surgeries through 2010 were prospectively reviewed.
ResultsWe found 12 studies from retrospective series and 15 case reports. To date, there are 43 reported cases of pouch-related cancers.
Thirty-two patients had cancer in the anal transit zone (ATZ); of these, 28 patients had mucosectomy. Eleven patients had
cancer found in the pouch body.
ConclusionRPC with mucosectomy does not necessarily eliminate risks. There is little evidence to support routine surveillance of pouch
mucosa and the ATZ except for patients associated with histological type C changes, sclerosing cholangitis, and unremitting
pouchitis.
KeywordsInflammatory bowel disease-associated colorectal cancer–Proctocolectomy–Mucosectomy–Pouch-related cancer
International Journal of Colorectal Disease 04/2012; 26(5):533-552. · 2.38 Impact Factor
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ABSTRACT: Colorectal cancer (CRC), the most lethal long-term complication of inflammatory bowel disease (IBD), is the culmination of a complex sequence of molecular and histologic derangements of the colon epithelium that are initiated and at least partially sustained by prolonged chronic inflammation. Dysplasia, the earliest histologic manifestation of this process, plays an important role in cancer prevention by providing the first clinical alert that this sequence is under way and by serving as an endpoint in colonoscopic surveillance of patients at high risk for CRC. Restorative proctocolectomy (RPC) is indicated for patients with IBD, specifically for ulcerative colitis that is refractory to medical treatment, emergency conditions, and/or in case of neoplastic transformation. Even after RPC with mucosectomy, pouch-related carcinomas have recently been reported with increasing frequency since the first report in 1984. We review IBD-associated CRC and pouch-related neoplasia prevalence, adverse events, risk factors, and surveillances.
Literature of IBD-associated CRC patients and those undergoing RPC surgeries through 2010 were prospectively reviewed.
We found 12 studies from retrospective series and 15 case reports. To date, there are 43 reported cases of pouch-related cancers. Thirty-two patients had cancer in the anal transit zone (ATZ); of these, 28 patients had mucosectomy. Eleven patients had cancer found in the pouch body.
RPC with mucosectomy does not necessarily eliminate risks. There is little evidence to support routine surveillance of pouch mucosa and the ATZ except for patients associated with histological type C changes, sclerosing cholangitis, and unremitting pouchitis.
International Journal of Colorectal Disease 02/2011; 26(5):533-52. · 2.38 Impact Factor
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ABSTRACT: The effect of 1,4-bis-(4-(1H-benzo[d]imidazol-2-yl-phenyl)) piperazine (BIPP), a newly synthesized piperazine derivative, on U937 leukemia cell viability was investigated. We show that BIPP induces dose-responsive apoptotic cell death in U937 cells by intrinsic mechanisms of apoptosis. Maximum apoptotic effect of BIPP on U937 cells was observed at 12.8μM. BIPP-induced apoptosis was evident by characteristics such as altered annexin-V binding, caspase activation, loss of mitochondrial membrane potential (MMP) and cytochrome c release. BIPP also differentially activates initiator and effector caspases combined with the loss of MMP strongly suggesting that BIPP causes an intrinsic apoptosis in U937 leukemia cells. Due to our observations that BIPP induces leukemia cell death without significantly affecting normal cells, our data suggests that it may be a potential therapeutic agent for human myeloid leukemia.
International journal of biochemistry and molecular biology. 01/2011; 2(1):78-88.
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ABSTRACT: The effects of flavonoids quercetin and genistein were investigated according to their potency to inhibit the oxidation of U937 cells via Fenton's pathway through the analysis of lipid peroxides and glutathione (GSH) levels. Human leukemia (U937) cells from the American Type Culture Collection were maintained at 37 degrees C for 24 h under 5% CO2 tension in RPMI-1640 medium containing 10% fetal bovine serum and 50 units ml(-1) each of penicillin and streptomycin. Cells were oxidized with iron 50 microM) or copper (50 microM) in H2O2 (0.01 mM) without or with a flavonoid sample (10 or 20 microM) for the lipid peroxidation studies. The GSH levels were measured (GSH Kit) before and after oxidation as above with different concentrations of flavonoids (0-40 microM). Lipid peroxide was measured by the thiobarbituric acid assay. Both quercetin and genistein at either the 10 or 20 microM level decreased lipid peroxidation significantly compared with their respective controls (P < 0.01). Lipid peroxides by Fe compared to the Cu-treated samples did not differ significantly from each other. However, the combination of flavonoids at the doses tested significantly (P < 0.001) decreased lipid peroxides, the effect being the same for both metal ions. The GSH levels increased significantly before exposure to the metal ions (for the different doses for the differences between the flavonoid samples and their respective untreated levels). For quercetin and genistein the increases in GSH above their untreated levels were 4.5, 8.3, 11.7 and 15 and 3.8, 7.9, 12.5 and 14.6 nmol 10(-6) cells, respectively, for the 5-40 microM levels tested for each flavonoid. Following the exposure to the metal ions, GSH levels remained almost the same for the different concentrations for each of the flavonoids tested but significantly above all of the controls and same for those of the untreated samples. The results indicate that both flavonoids inhibited lipid peroxides and the inhibition may be attributed to the prevention of loss of intracellular GSH levels in U937 cells.
Journal of Applied Toxicology 25(1):82-8. · 2.48 Impact Factor
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ABSTRACT: The single and combined effects of two abundant flavonoids, namely quercetin and genistein, were investigated according to their ability to inhibit the oxidation of methyl linolenate via Fenton's pathway. Antioxidative activity was determined by oxidizing methyl linolenate suspended in a buffer solution with either Fe2+ (50 microM) or Cu2+ (50 microM) and hydrogen peroxide (0.01 mM) without or with a flavonoid sample (10 or 20 microM). Lipid peroxidation products were measured by the thiobarbituric acid (TBA) assay and the amounts of thiobarbituric acid-reactive substances (TBARS) were calculated from a calibration curve using 1,1,3,3-tetraethoxypropane as the standard. Both quercetin and genistein at the 10 or 20 microM level decreased lipid peroxidation significantly compared with their respective controls. Of the two flavonoids tested, quercetin had a more marked effect on inhibiting lipid peroxides. Peroxidation products for the control samples were higher for the Fe2+-treated samples compared with the Cu2+ samples. Combination of both flavonoids at the same dose levels continued to decrease lipid peroxidation, the effect being the same for both metal ions. The data suggest that the combined flavonoids offered better protection than the single treatments and this may be attributed to the better radical scavenging or increased chelating capabilities of the combined over the single treatments. The differences in peroxide levels for the single treatment of quercetin compared with the genistein-treated samples may reflect the structural differences between these compounds in combating oxidative stress.
Journal of Applied Toxicology 23(5):363-9. · 2.48 Impact Factor
