Antioxidants and micronutrients.
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Antioxidants↗
Biomedical subjects
Emmanuel C Opara
Publications and source records attributed to Emmanuel C Opara.
Effect of alginate composition and gelling cation on micro-bead swelling.
PURPOSE: The purpose of this study was to determine the roles of alginate composition and gelling cations on bead swelling, which affects its durability. METHOD: Using a 2-channel droplet generator, microspheres were generated with 1.5% solutions of low viscosity high-mannuronic acid (LVM), medium viscosity high-mannuronic acid (MVM), low viscosity high-guluronic acid (LVG) and medium viscosity high-guluronic acid (MVG) alginate. They were gelled by cross-linking with 1.1% solution of either BaCl2 or CaCl2. The diameters of the micro-beads were measured and recorded on day 0. The micro-beads were subsequently washed and incubated in saline at 37 degrees C for 2 weeks with size assessment every 2 days. The data were normalized by calculation of the percentage change from control (day 0) for all groups of micro-beads. RESULTS: Diameters of all beads were between 550 and 700 microm on day 0. Viscosity had no effect on swelling of Ba++- and Ca++-alginate micro-beads. Ca++-alginate micro-beads were more prone to swelling than the corresponding Ba++-alginate beads. High G-Ba++ beads had only a modest increase in size over time, in contrast to the high M-Ba++. CONCLUSION: Alginate composition and the gelling cation have significant effects on bead swelling.
Alginates↗
Effect of alginate composition and gelling cation on microbead swelling.
PURPOSE: The purpose of this study was to determine the roles of alginate composition and gelling cations on bead swelling, which affects its durability. METHOD: Using a 2-channel droplet generator, microspheres were generated with 1.5% solutions of low viscosity high-mannuronic acid (LVM), medium viscosity high-mannuronic acid (MVM), low viscosity high-guluronic acid (LVG) and medium viscosity high-guluronic acid (MVG) alginate. They were gelled by cross-linking with 1.1% solution of either BaCl2 or CaCl2. The diameters of the microbeads were measured and recorded on day 0. The microbeads were subsequently washed and incubated in saline at 37 degrees C for 2 weeks with size assessment every 2 days. The data were normalized by calculation of the percentage change from control (day 0) for all groups of microbeads. RESULTS: Diameters of all beads were between 550-700 microns on day 0. Viscosity had no effect on swelling of Ba++- and Ca++-alginate microbeads. Ca++-alginate microbeads were more prone to swelling than the corresponding Ba++-alginate beads. High G-Ba++ beads had only a modest increase in size over time, in contrast to the high M-Ba++. CONCLUSION: Alginate composition and the gelling cation have significant effects on bead swelling.
Alginates↗
Effects of esomeprazole magnesium on nonsteroidal anti-inflammatory drug gastropathy.
It has been proposed that tissue damage induced by nonsteroidal anti-inflammatory drugs is related to increased tissue free radical production with antioxidant depletion. We have shown that esomeprazole increases gastric total antioxidant capacity in mice and, therefore, hypothesized that the protective effect of esomeprazole during treatment with a nonsteroidal anti-inflammatory drug is related to increased gastric antioxidant capacity and decreased tissue free radical production. A/J mice received one of four treatments by daily gavage: saline in vehicle (control), indomethacin, esomeprazole, or indomethacin and esomeprazole. After 10 days, all mice were sacrificed and validated assays were used to measure gastric total antioxidant capacity, lipid peroxide levels, and myeloperoxidase activity. Indomethacin-treated mice developed weight loss and melena. No mice receiving indomethacin and esomeprazole died, but the death rate while receiving indomethacin was 38% (chi2, P = 0.05). Gastric lipid peroxide levels increased in mice receiving indomethacin treatment compared to treatment with esomeprazole and indomethacin (P = 0.03). There was a strong trend (P = 0.08) toward increased gastric total antioxidant capacity in mice receiving esomeprazole and indomethacin compared to mice receiving indomethacin. Gastric myeloperoxidase activities were not different among the four groups. Esomeprazole significantly improved survival in mice that received indomethacin, reduced free radical production, as estimated by lipid peroxide levels, and appeared to increase gastric total antioxidant capacity. The mechanisms for the beneficial effects of esomeprazole in the treatment of gastropathy are more complex than previously thought.
Animals↗
Characteristics of Poly-L-Ornithine-coated alginate microcapsules.
Poly-L-Lysine (PLL) is the most widely used biomaterial for providing perm-selectivity in alginate microcapsules for islet transplantation. We had previously reported that Poly-L-Ornithine (PLO) is less immunogenic than PLL, and in the present study, we have compared the physical characteristics of PLO- and PLL-coated hollow alginate microcapsules. Microspheres made with 1.5% alginate were divided into 2 groups that were first coated with either 0.1% PLO or PLL, followed by a second coating with 0.25% alginate. After liquefaction of the inner alginate core with sodium citrate, the microcapsules were washed with saline and used for experiments. Pore size exclusion studies were performed with FITC-labeled lectins incubated with encapsulated pig islets followed by examination for fluorescence activity. Mechanical strength was assessed by an osmotic pressure test and by 36 h of mechanical agitation of microcapsules with inert soda lime beads. The pore size exclusion limit of microcapsules after 20 min of coating was significantly smaller with PLO. While the mean +/- SEM diameter of PLL-coated microcapsules increased from 718+/-17 to 821 +/- 17 microm (p < 0.05) during 14 days incubation at 37 degrees C, the PLO group did not change in size. Also, PLL group had a higher percentage of broken capsules (52.7 +/- 4.9%) compared to 3.1 +/- 2.05% for PLO capsules (p < 0.0001,n = 6). We conclude that PLO-coated alginate microcapsules are mechanically stronger and provide better perm-selectivity than PLL-coated microcapsules.
Alginates↗
Effect of the H, K-ATPase inhibitor, esomeprazole magnesium, on gut total antioxidant capacity in mice.
Antioxidant depletion is believed to be a mechanism involved in the pathophysiology of several upper gastrointestinal disorders, and H, K-ATPase inhibitors can alter free radical production by neutrophils. We hypothesized that the H, K-ATPase inhibitor esomeprazole magnesium would decrease gut free radical production with a concomitant increase in gut total antioxidant capacity. A/J mice (n = 10/group) received either vehicle (control) or one of three concentrations of esomeprazole magnesium in vehicle by once-daily gavage for 10 days. Using tissue extracts from stomach and colon, total antioxidant capacity, lipid peroxide levels, and constitutive Cu/Zn-superoxide dismutase were measured using validated assays. There was a dose-related increase in total antioxidant capacity (analysis of variance, P < 0.001) in stomach, but there was no change in the colon. In the assessment of free radical production, there was a trend toward decreased lipid peroxide levels in stomach from mice receiving esomeprazole. In stomach, Cu/Zn-superoxide dismutase activity was increased (ANOVA: p=.03) in mice receiving esomeprazole. In conclusion, gastric total antioxidant capacity and Cu/Zn-superoxide dismutase activity are increased by esomeprazole, and these changes may result in part from decreased free radical production. The present results support the notion that the pharmacological effects of this agent on upper intestinal tissue are more complex than previously thought, and appear to involve both enzymatic and nonenzymatic tissue antioxidants.
Animals↗
Role of oxidative stress in the etiology of type 2 diabetes and the effect of antioxidant supplementation on glycemic control.
Oxidative stress is a situation in which the amount of reactive oxygen species (ROS) exceeds the levels of neutralizing substances referred to as antioxidants. Numerous studies have shown that oxidative stress is associated with type 2 diabetes, and there is compelling biochemical evidence that suggests that ROS may even play a role, if only secondary, in the pathogenesis of type 2 diabetes. These observations have provided sufficient impetus for the use of antioxidant supplements as adjunct therapy for control of blood sugar in diabetic patients. However, there is currently no optimum regimen of antioxidant supplementation for diabetic patients. Studies are required to determine appropriate doses of relevant individual micronutrients that perhaps should be used in combination to diminish oxidative stress and improve glycemic control in individuals afflicted with type 2 diabetes.
Antioxidants↗
Oxidative stress in nonalcoholic fatty liver disease: pathogenesis and antioxidant therapies.
Nonalcoholic fatty liver disease is a common cause of chronic liver disease, a common finding on liver biopsy in those patients with abnormal blood transaminase levels, and a common cause of cryptogenic cirrhosis in the United States. The prevalence of this disorder is expected to rise with the increase in obesity, and the clinical spectrum can range from simple steatosis (fatty liver) to cirrhosis of the liver. Insulin resistance is thought to be pivotal for the development of steatosis, and oxidative stress may be a potential factor that can promote hepatic necroinflammation and fibrosis. Preliminary studies have examined the role of oxidative stress and antioxidants in animal and human studies of this disorder. Efforts to improve the hepatic antioxidant system could be achieved by optimizing the patient's diet, by supplementation with precursors for antioxidants, or by supplementation with essential metals and/or antioxidants. Randomized, controlled trials are required to examine these potential approaches using patients with this disorder.
Animals↗
Polyvinyl pyrrolidone: a novel cryoprotectant in islet cell cryopreservation.
The present study was performed on the basis of the hypothesis that the low molecular weight (MW) compounds, DMSO and glycerol, permeate the cell and interact hydrophobically with intracellular proteins, thereby perturbing the cytoskeletal architecture of frozen cells and diminishing islet cell integrity and function. Isolated rat islets were cultured overnight (18-24 h) at 37 degrees C in RPMI medium supplemented with 10% fetal calf serum and 1% mixture of penicillin/streptomycin. Using a programmable temperature controller, samples of precounted islets were then frozen under liquid nitrogen, in the presence of either 2 M DMSO (MW = 0.078 kDa), 3 M glycerol (MW = 0.092 kDa), 5% polyethylene glycol (PEG, MW = 20 kDa), or 10% polyvinylpyrrolidone (PVP, MW = 40 kDa), and stored at -80 degrees C for 1 week. Following thawing and overnight (18-24 h) culture, intact islet recovery was determined by islet counting after dithizone staining. Islet function was assessed by determination of glucose-stimulated insulin secretion in perifusion experiments with Krebs-Ringer bicarbonate buffer, pH 7.4, containing either basal (3.3 mM) or high (16.7 mM) glucose concentrations. The assessment of islet recovery and function of all cryopreserved samples was performed only after thawing and overnight culture (18-24 h) of islets. The mean +/- SEM percent intact islet recovery was higher with PVP compared with DMSO (82 +/- 4.6 vs. 62.7 +/- 3.1%, respectively, p < 0.005, n = 9). Furthermore, the glucose stimulation index of insulin secretion by islets taken from samples frozen with PEG and PVP, after thawing and overnight culture, was comparable to that of freshly isolated islets, in contrast to DMSO and glycerol. There was no significant difference in intact islet recovery and function between samples frozen with PVP and those frozen with PEG. Samples frozen with DMSO and glycerol had similar results in islet recovery and function. These data show that PVP is a new and potent cryoprotectant for islet cell freezing.
Animals↗
Total antioxidant capacity following extrinsic denervation and small intestinal transplantation in the rat.
Transplantation of small intestine in a rat model has been shown to affect expression of neurochemicals within enteric inhibitory nerves. However, the mechanism for altered expression of inhibitory neurochemicals is uncertain. Based on our previous studies, we hypothesized that small intestinal transplantation would result in altered intestinal levels of antioxidant capacity. Glutathione, total antioxidant capacity, and lipid peroxide levels were measured at 3 months following (1) transection of rat small intestine, (2) transection and extrinsic denervation of rat intestine, and (3) isotransplantation of rat ileum or (4) allotransplantation of rat ileum with cyclosporine therapy to suppress rejection. Glutathione levels were not significantly different among the four groups. There were trends toward increased lipid peroxide levels following isografting and extrinsic denervation. Total antioxidant capacity was increased following extrinsic denervation (P=0.05). Increased intestinal total antioxidant capacity in response to extrinsic denervation may represent a compensatory mechanism for protection against oxidative stress. This result enhances our understanding of the relationship between tissue antioxidant levels and alteration of enteric nerves.
Animals↗
Effects of omeprazole and ascorbate on gastric emptying and antioxidant levels in a mouse model of glutathione depletion.
Increased free radical production with depletion of the antioxidant, glutathione, is a suggested mechanism for the development of ulcer disease in patients with Helicobacter pylori. The effects of ascorbate and omeprazole as potential gut antioxidants are incompletely understood. We hypothesized that as antioxidants, ascorbate and omeprazole protect against glutathione depletion. This study was designed to determine the effects of ascorbate and omeprazole on gastric emptying and gastric antioxidant levels in a mouse model of glutathione depletion. In an acute (10-day) mouse model, glutathione depletion was induced by inhibiting the rate limiting enzyme, gamma-glutamylcysteine synthetase. Enzymatic blockade produced depletion of gastric glutathione (P < 0.05) without increasing gastric lipid hydroperoxides. Glutathione depletion was associated with accelerated liquid gastric emptying. These effects were not prevented by supplementation with ascorbate or omeprazole. Omeprazole induced increased (P < 0.05) gastric and colonic total antioxidant capacity. One of the beneficial effects of omeprazole in patients may involve increased total antioxidant capacity.
Animals↗
Immunoisolation techniques for islet cell transplantation.
Diabetes remains a devastating disease, with tremendous cost in terms of human suffering and healthcare expenditures. The burden of diabetes is primarily related to the multiple complications, including retinopathy, nephropathy, neuropathy and cardiovascular disease that can develop as the disease progresses. It has been shown that these complications can be prevented, and in some cases, reversed by islet cell transplantation, which, until recently, had remained elusive as a viable routine treatment modality. In recent studies, islet cell transplantation has shown great promise as a viable alternative to solid pancreas transplantation. However, severe shortage of human pancreases and the need to use immunosuppressive drugs to prevent transplant rejection, remain major obstacles to routine use of islet cell transplants for the treatment of patients with Type 1 diabetes. In the attempt to overcome these barriers, many procedures have been designed to immunoisolate islet cells for transplantation. The ultimate goal in islet cell transplantation is the availability of unlimited supply of cells to be transplanted in a simple procedure performed with little or no use of immunosuppressive drugs. The development of reliable procedures to immunoisolate islets by microencapsulation prior to transplantation has a great deal of potential to accomplish this objective.
Animals↗