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Andrew A House - One of the best experts on this subject based on the ideXlab platform.
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Mesna for treatment of hyperhomocysteinemia in hemodialysis patients a placebo controlled double blind randomized trial
Clinical Journal of The American Society of Nephrology, 2008Co-Authors: Bradley L. Urquhart, Murray J. Cutler, David J Freeman, David J Spence, Rahul Mainra, Andrew A HouseAbstract:Background and objectives: Increased plasma total homocysteine is a graded, independent risk factor for the development of atherosclerosis and thrombosis. More than 90% of patients with end-stage renal disease have hyperhomocysteinemia despite vitamin supplementation. It was shown in previous studies that a single intravenous dose of Mesna 5 mg/kg caused a drop in plasma total homocysteine that was significantly lower than predialysis levels 2 d after dosing. It was hypothesized 5 mg/kg intravenous Mesna administered thrice weekly, before dialysis, for 8 wk would cause a significant decrease in plasma total homocysteine compared with placebo. Design, setting, participants, & measurements: Patients with end-stage renal disease were randomly assigned to receive either intravenous Mesna 5 mg/kg or placebo thrice weekly before dialysis. Predialysis plasma total homocysteine concentrations at weeks 4 and 8 were compared between groups by paired t test. Results: Mean total homocysteine at 8 wk in the placebo group was 24.9 μmol/L compared with 24.3 μmol/L in the Mesna group (n = 22 [11 pairs]; mean difference 0.63). Interim analysis at 4 wk also showed no significant difference between Mesna and placebo (n = 32 [16 pairs]; placebo 26.3 μmol/L, Mesna 24.5 μmol/L; mean difference 1.88). Multivariable adjustments for baseline characteristics did not alter the analysis. Plasma Mesna seemed to reach steady-state concentrations by 4 wk. Conclusions: It is concluded that 5 mg/kg Mesna does not lower plasma total homocysteine in hemodialysis patients and that larger dosages may be required.
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Mesna as a nonvitamin intervention to lower plasma total homocysteine concentration implications for assessment of the homocysteine theory of atherosclerosis
The Journal of Clinical Pharmacology, 2007Co-Authors: Bradley L. Urquhart, David J Freeman, David J Spence, Andrew A HouseAbstract:Abstract Elevated plasma total homocysteine is independently associated with atherosclerosis. Recent randomized trials show that vitamins lower total homocysteine but do not prevent cardiovascular events, suggesting the need for nonvitamin therapies to evaluate whether a causative relationship exists. Mesna (sodium 2-mercaptoethanesulfonate) is a thiol-containing drug capable of liberating homocysteine bound by disulfide bonds to proteins, facilitating its excretion. The effect of oral Mesna on total homocysteine has not been evaluated and was the objective of this study. Eleven healthy volunteers received vehicle or 10 mg/kg Mesna in random order, after which serial blood and urine samples were collected over 4 hours. Plasma total homocysteine decreased by 24.2% (P < .0001) following Mesna. Urinary homocysteine excretion was significantly greater with Mesna (3.9 +/- 2.4 mumol) compared to vehicle (0.4 +/- 0.1 mumol), P < .01. Oral Mesna decreases plasma total homocysteine and is a potential nonvitamin treatment for assessing the homocysteine theory of atherosclerosis.
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the effect of Mesna on plasma total homocysteine concentration in hemodialysis patients
American Journal of Kidney Diseases, 2007Co-Authors: Bradley L. Urquhart, David J Freeman, David J Spence, Andrew A HouseAbstract:Background Plasma total homocysteine (tHcy) level is an independent risk factor for the development of atherosclerosis. The degree of risk in most of the population is decreased by using dietary vitamin supplementation; however, more than 90% of patients with end-stage renal disease have increased tHcy levels despite supplementation. Only a small fraction of tHcy is removed by hemodialysis because of extensive disulfide bonding to albumin. The objective of this study is to determine whether a single intravenous dose of Mesna, a thiol-containing drug analogue of taurine, facilitates tHcy clearance during hemodialysis. Methods Initial in vitro thiol exchange tests were performed with Mesna in plasma from dialysis patients. Mesna, 300 μmol/L (49.2 mg/L), was incubated with plasma at 37°C, and free homocysteine was measured at various times. In vivo, Mesna activity was tested in 10 hemodialysis patients by administering 2.5 or 5.0 mg/kg of Mesna intravenously at the beginning of a treatment cycle. Blood samples were drawn throughout dialysis, and plasma tHcy levels were compared with those obtained from a previous dialysis session in which Mesna was not administered. Results In vitro, Mesna liberated 36.5% ± 2.5% of protein-bound homocysteine in 30 minutes. In vivo, a single 2.5-mg/kg dose of Mesna was ineffective; however, at 5.0 mg/kg, it caused a 55.2% ± 3.9% decrease in plasma tHcy levels postdialysis compared with a 34.2% ± 5.3% decrease with dialysis alone ( P Conclusion Intravenous Mesna causes a rapid decrease in plasma tHcy levels during hemodialysis.
Bradley L. Urquhart - One of the best experts on this subject based on the ideXlab platform.
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In vitro and in vivo assessment of renal drug transporters in the disposition of Mesna and diMesna.
The Journal of Clinical Pharmacology, 2011Co-Authors: Murray J. Cutler, Thomas J. Velenosi, Bradley L. Urquhart, Brenda F. Leake, Henriette E. Meyer Zu Schwabedissen, Rommel G. Tirona, George K Dresser, Dave FreemanAbstract:Abstract Mesna and its dimer, diMesna, are coadministered for mitigation of ifosfamide- and cisplatin-induced toxicities, respectively. DiMesna is selectively reduced to Mesna in the kidney, producing its protective effects. In vitro screens of uptake and efflux transporters revealed saturable uptake by renal organic anion transporters OAT1, OAT3, and OAT4. Efflux transporters breast cancer resistance protein; multidrug and toxin extrusion 1 (MATE1); multidrug resistance proteins MRP1, MRP2, MRP4, and MRP5; and P-glycoprotein (Pgp) significantly reduced diMesna accumulation. Further investigation demonstrated that renal apical efflux transporters MATE1, MRP2, and Pgp were also capable of Mesna efflux. Administration of OAT inhibitor probenecid to healthy subjects significantly increased combined Mesna and diMesna plasma exposure (91% ± 34%) while decreasing the renal clearance due to net secretion (67.0% ± 12.7%) and steady-state volume of distribution (45.2% ± 13.4%). Thus, the kidney represents a significant sink of total Mesna, whereas function of renal drug transporters facilitates clearance in excess of glomerular filtration rate and likely the presence of active Mesna in the urine. Loss of renal transporter function due to genetic variability or drug-drug interactions may decrease the efficacy of chemoprotectants, increasing the risk of ifosfamide- and cisplatin-induced toxicities.
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Mesna for treatment of hyperhomocysteinemia in hemodialysis patients a placebo controlled double blind randomized trial
Clinical Journal of The American Society of Nephrology, 2008Co-Authors: Bradley L. Urquhart, Murray J. Cutler, David J Freeman, David J Spence, Rahul Mainra, Andrew A HouseAbstract:Background and objectives: Increased plasma total homocysteine is a graded, independent risk factor for the development of atherosclerosis and thrombosis. More than 90% of patients with end-stage renal disease have hyperhomocysteinemia despite vitamin supplementation. It was shown in previous studies that a single intravenous dose of Mesna 5 mg/kg caused a drop in plasma total homocysteine that was significantly lower than predialysis levels 2 d after dosing. It was hypothesized 5 mg/kg intravenous Mesna administered thrice weekly, before dialysis, for 8 wk would cause a significant decrease in plasma total homocysteine compared with placebo. Design, setting, participants, & measurements: Patients with end-stage renal disease were randomly assigned to receive either intravenous Mesna 5 mg/kg or placebo thrice weekly before dialysis. Predialysis plasma total homocysteine concentrations at weeks 4 and 8 were compared between groups by paired t test. Results: Mean total homocysteine at 8 wk in the placebo group was 24.9 μmol/L compared with 24.3 μmol/L in the Mesna group (n = 22 [11 pairs]; mean difference 0.63). Interim analysis at 4 wk also showed no significant difference between Mesna and placebo (n = 32 [16 pairs]; placebo 26.3 μmol/L, Mesna 24.5 μmol/L; mean difference 1.88). Multivariable adjustments for baseline characteristics did not alter the analysis. Plasma Mesna seemed to reach steady-state concentrations by 4 wk. Conclusions: It is concluded that 5 mg/kg Mesna does not lower plasma total homocysteine in hemodialysis patients and that larger dosages may be required.
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Mesna as a nonvitamin intervention to lower plasma total homocysteine concentration implications for assessment of the homocysteine theory of atherosclerosis
The Journal of Clinical Pharmacology, 2007Co-Authors: Bradley L. Urquhart, David J Freeman, David J Spence, Andrew A HouseAbstract:Abstract Elevated plasma total homocysteine is independently associated with atherosclerosis. Recent randomized trials show that vitamins lower total homocysteine but do not prevent cardiovascular events, suggesting the need for nonvitamin therapies to evaluate whether a causative relationship exists. Mesna (sodium 2-mercaptoethanesulfonate) is a thiol-containing drug capable of liberating homocysteine bound by disulfide bonds to proteins, facilitating its excretion. The effect of oral Mesna on total homocysteine has not been evaluated and was the objective of this study. Eleven healthy volunteers received vehicle or 10 mg/kg Mesna in random order, after which serial blood and urine samples were collected over 4 hours. Plasma total homocysteine decreased by 24.2% (P < .0001) following Mesna. Urinary homocysteine excretion was significantly greater with Mesna (3.9 +/- 2.4 mumol) compared to vehicle (0.4 +/- 0.1 mumol), P < .01. Oral Mesna decreases plasma total homocysteine and is a potential nonvitamin treatment for assessing the homocysteine theory of atherosclerosis.
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the effect of Mesna on plasma total homocysteine concentration in hemodialysis patients
American Journal of Kidney Diseases, 2007Co-Authors: Bradley L. Urquhart, David J Freeman, David J Spence, Andrew A HouseAbstract:Background Plasma total homocysteine (tHcy) level is an independent risk factor for the development of atherosclerosis. The degree of risk in most of the population is decreased by using dietary vitamin supplementation; however, more than 90% of patients with end-stage renal disease have increased tHcy levels despite supplementation. Only a small fraction of tHcy is removed by hemodialysis because of extensive disulfide bonding to albumin. The objective of this study is to determine whether a single intravenous dose of Mesna, a thiol-containing drug analogue of taurine, facilitates tHcy clearance during hemodialysis. Methods Initial in vitro thiol exchange tests were performed with Mesna in plasma from dialysis patients. Mesna, 300 μmol/L (49.2 mg/L), was incubated with plasma at 37°C, and free homocysteine was measured at various times. In vivo, Mesna activity was tested in 10 hemodialysis patients by administering 2.5 or 5.0 mg/kg of Mesna intravenously at the beginning of a treatment cycle. Blood samples were drawn throughout dialysis, and plasma tHcy levels were compared with those obtained from a previous dialysis session in which Mesna was not administered. Results In vitro, Mesna liberated 36.5% ± 2.5% of protein-bound homocysteine in 30 minutes. In vivo, a single 2.5-mg/kg dose of Mesna was ineffective; however, at 5.0 mg/kg, it caused a 55.2% ± 3.9% decrease in plasma tHcy levels postdialysis compared with a 34.2% ± 5.3% decrease with dialysis alone ( P Conclusion Intravenous Mesna causes a rapid decrease in plasma tHcy levels during hemodialysis.
Goksel şener - One of the best experts on this subject based on the ideXlab platform.
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protective effect of Mesna 2 mercaptoethane sulfonate against hepatic ischemia reperfusion injury in rats
Surgery Today, 2005Co-Authors: Goksel şener, Ozer A şehirli, Nursal Gedik, Feriha Ercan, Serap Sirvanci, Ayhan KacmazAbstract:Purpose Reoxygenation of ischemic tissue generates various reactive oxygen metabolites (ROMs), which have a deleterious effect on various cellular functions. We evaluated the possible protective effect of 2-mercaptoethane sulfonate (Mesna) on hepatic ischemia/reperfusion (I/R) injury.
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protective effects of Mesna 2 mercaptoethane sulphonate against acetaminophen induced hepatorenal oxidative damage in mice
Journal of Applied Toxicology, 2005Co-Authors: Goksel şener, Ozer A şehirli, şule Cetinel, Nursal Gedik, Berrak G Yegen, Gul AyanogludulgerAbstract:Acetaminophen, a widely used analgesic and antipyretic, is known to cause hepatic and renal injury in humans and experimental animals when administered in high doses. It was reported that these toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. In this study we aimed to investigate the possible beneficial effect of 2-mercaptoethane sulphonate (Mesna), an antioxidant agent, against acetaminophen toxicity in mice. Balb-c mice were injected i.p. with: vehicle (the control group); a single dose of 150 mg kg(-1) Mesna (MES group); a single dose of 900 mg kg(-1) i.p. acetaminophen (AA4h and AA24h groups); and Mesna, at a dose of 150 mg kg(-1) after acetaminophen injection (AA4h-MES and AA24h-MES groups). The Mesna injection was repeated once more 12 h after the first injection in the AA24h-MES group. Blood urea nitrogen, serum creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood and glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver and kidney tissues were measured. Tissues also were examined microscopically. Blood urea nitrogen and serum creatinine, which were increased significantly (P < 0.001) following acetaminophen treatment were decreased significantly (P < 0.05-0.001) after treatment with Mesna. The ALT and AST levels were also increased significantly (P < 0.001) after acetaminophen treatment but were not reduced with Mesna. Acetaminophen treatment caused a significant (P < 0.05-0.001) decrease in GSH levels whereas MDA levels and MPO activity were increased in both tissues. These changes were reversed by Mesna treatment. Collagen contents of the liver and kidney tissues were increased by acetaminophen treatment (P < 0.001) and reversed back to the control levels with Mesna. Our results imply that acetaminophen causes oxidative damage in hepatic and renal tissues and that Mesna, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role as a 'tissue injury-limiting agent' must be elucidated further in drug-induced oxidative damage.
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Mesna 2 mercaptoethane sulfonate prevents ischemia reperfusion induced renal oxidative damage in rats
Life Sciences, 2004Co-Authors: Levent Kabasakal, Ozer A şehirli, şule Cetinel, Esra Cikler, Nursal Gedik, Goksel şenerAbstract:Abstract Reoxygenation of the ischemic tissue promotes the generation of various reactive oxygen metabolites (ROM) which are known to have deleterious effects on various cellular functions. This study was designed to determine the possible protective effect of Mesna (2-Mercaptoethane Sulfonate) on renal ischemia/reperfusion (I/R) injury. Wistar albino rats were unilaterally nephrectomized, and 15 days later they were subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Mesna (Mesna, 150 mg/kg, i.p.; an effective dose against I/R injury) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. Kidney samples were taken for histological examination or determination of the free radicals, renal malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Renal tissue collagen content, as a fibrosis marker was also determined. Creatinine and urea concentrations in blood were measured for the evaluation of renal function. The results demonstrated that renal I/R caused nephrotoxicity, as evidenced by increases in blood urea and creatinine levels, which was reversed by Mesna treatment. Increased free radical levels, as assessed by nitroblue-tetrazolium test were reduced with Mesna. Moreover, the decrease in GSH and increases in MDA levels, and MPO activity induced by I/R indicated that renal injury involves free radical formation. Treatment of rats with Mesna restored the reduced GSH levels while it decreased MDA levels as well as MPO activity. Increased collagen contents of the kidney tissues by I/R were reversed back to the control levels by Mesna treatment. Since Mesna administration reversed these oxidant responses, improved renal function and microscopic damage, it seems likely that Mesna protects kidney tissue against I/R induced oxidative damage.
Kazuki Sumiyama - One of the best experts on this subject based on the ideXlab platform.
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a feasibility study of chemically assisted endoscopic submucosal mechanical dissection using Mesna for superficial esophageal squamous cell carcinomas
Surgical Endoscopy and Other Interventional Techniques, 2015Co-Authors: Akira Dobashi, Kazuki Sumiyama, Hirobumi Toyoizumi, Tomohiko R Ohya, Masakuni Kobayashi, Kenichi Goda, Masayuki Kato, Tomohiro Kato, Masato Matsushima, Hisao TajiriAbstract:Background Injection of Mesna into submucosal layers was recently reported to chemically soften connective tissue and facilitate the gastric endoscopic submucosal dissection (ESD) procedure. This study aimed to evaluate the safety and feasibility of similarly using Mesna for esophageal ESD (Mesna ESD).
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chemically assisted peroral endoscopic myotomy with submucosal Mesna injection in a porcine model
Minimally Invasive Therapy & Allied Technologies, 2015Co-Authors: Yosuke Kawahara, Kazuki Sumiyama, Hisao TajiriAbstract:AbstractBackground: Peroral endoscopic myotomy (POEM) is a less invasive alternative to standard surgery for the treatment of achalasia. Previous studies have demonstrated that submucosal injections of Mesna soften tissues and facilitate endoscopic submucosal dissection. Material and methods: We studied the technical feasibility of a chemically assisted POEM procedure with Mesna injection (CA-POEM) in ten pigs compared with POEM with saline injection in five pigs. We also compared two dissection techniques in CA-POEM, diathermy needle knife dissection (n = 5) and balloon mechanical dissection (n = 5). A 10 cm esophageal submucosal tunnel was created with a needle knife or with balloon mechanical dissection following Mesna or saline submucosal injection. Approximately 5 cm of inner circular muscle was then dissected within the tunnel. The tunnel was closed with endoclip application at the mucosal endoscopic entry point. Pigs were sacrificed one week post procedure. Results: All procedures were successful a...
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a double blind block randomized placebo controlled trial to identify the chemical assistance effect of Mesna submucosal injection for gastric endoscopic submucosal dissection
Gastrointestinal Endoscopy, 2014Co-Authors: Kazuki Sumiyama, Hirobumi Toyoizumi, Tomohiko R Ohya, Akira Dobashi, Shoryoku Hino, Masakuni Kobayashi, Kenichi Goda, Hiroo Imazu, Yumi Kawakita, Tomohiko KatoAbstract:Background Previous animal studies and a pilot clinical trial demonstrated that submucosal injection of a thiol compound called Mesna could chemically soften connective tissues and thus facilitate endoscopic submucosal dissection (ESD). Objective To evaluate whether Mesna injection could reduce procedural times for gastric ESD. Design Double-blind, block-randomized, controlled trial. Setting University hospital. Patients A total of 101 patients with superficial gastric cancer indicated for ESD were enrolled and randomly assigned to either the Mesna or control (saline solution) group. Intervention Traditional ESD was performed with a single bolus injection of Mesna or saline solution. Main Outcome Measurements Time for submucosal dissection (TSD). Results En bloc resection was achieved for all lesions in the Mesna group (53/53) and 51 of 52 lesions (98.08%) in the control group. TSD was not statistically different between the groups (18.62 ± 13.9 [mean ± SD] minutes for the Mesna group and 24.58 ± 24.55 [mean ± SD] minutes for the control group; P = .128), and there were fewer time-consuming cases (times over 30 minutes) in the Mesna group compared with controls (7/53 vs 15/52; P = .049). Multivariate regression analysis demonstrated that use of Mesna, specimen size, and the presence of fibrous scars were significantly correlated with TSD ( P .05). Limitations Single-center study. Conclusion TSD was not significantly different between the Mesna and control injection groups, but multivariate analysis indicated that Mesna injection reduced procedural challenges associated with the submucosal dissection. (Clinical trial registration number: UMIN000003786.)
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chemically assisted endoscopic mechanical submucosal dissection by using Mesna
Gastrointestinal Endoscopy, 2008Co-Authors: Kazuki Sumiyama, Christopher J Gostout, Elizabeth Rajan, Timothy A Bakken, Mary A KnipschieldAbstract:Background A class of thiol compounds, Mesna (sodium-2-mercaptoethanesulfonate), has been used to facilitate tissue dissection in surgical fields. Objectives To evaluate the technical feasibility and efficacy of chemically assisted endoscopic mechanical submucosal dissection (CAEMSD) by using Mesna. Design An in vivo controlled blind trial by using porcine models. Settings Nonsurvival study in an animal laboratory. Interventions Six pigs were studied. Mucosal targets of about 2 cm (estimated) for treatment were created with a circle of cauterized spots along the greater curvature of the gastric body and the antrum. A Mesna solution or the control hydroxypropyl methylcellulose solution was submucosally injected. The target mucosa was mechanically isolated with balloon dissection and removed by circumferential incision with a hook-knife inserted into the submucosal space. Necropsy and mucosal specimens from both groups were examined by histology. Results En bloc resection of the target was achieved in all 8 attempts of the Mesna group and in 7 of 8 attempts of the control group. Use of Mesna significantly reduced tissue resistance to the initial balloon-catheter insertion into the submucosa and the technical difficulty of subsequent submucosal balloon dissection by using a subjective grading system ( P Conclusions CAEMSD is a unique methodology to facilitate mucosal resection.
Constantinos Simopoulos - One of the best experts on this subject based on the ideXlab platform.
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Mesna protects splanchnic organs from oxidative stress induced by pneumoperitoneum
Surgical Endoscopy and Other Interventional Techniques, 2009Co-Authors: Petros Ypsilantis, Ioannis Tentes, Konstantinos Anagnostopoulos, Alexandros Kortsaris, Constantinos SimopoulosAbstract:We investigated the potential beneficial effect of the antioxidant 2-mercaptoethane-sulfonate (Mesna) against oxidative stress induced by pneumoperitoneum in splanchnic organs. Wistar rats were subjected to either (a) CO2 pneumoperitoneum (15 mmHg for 60 min) (group P), (b) pretreatment with Mesna (400 mg/kg, p.o.) followed by pneumoperitoneum with a 180 min interval (group MP), (c) sham operation (group S), or (d) administration of Mesna only (group M). Forty-five minutes after desufflation (groups P and MP), 60 + 45 min after the induction of anesthesia (group S), or 180 min after Mesna administration (group M), tissue specimens were excised from liver, kidneys, jejunum and stomach. Tissue oxidative state was assessed on the basis of glutathione-to-glutathione disulfide ratio, malondialdehyde concentration , and superoxide dismutase activity. Pneumoperitoneum deteriorated all the oxidative stress markers in the organs studied. Mesna prevented the occurrence of oxidative stress following pneumoperitoneum in all the organs studied. In the absence of pneumoperitoneum, the administration of Mesna caused mild enhancement of the oxidative state of liver, stomach, and kidneys compared to sham controls. Prophylaxis with Mesna prevents oxidative stress induced by pneumoperitoneum in splanchnic organs.
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prophylaxis with Mesna prevents oxidative stress induced by ischemia reperfusion in the intestine via inhibition of nuclear factor κb activation
Journal of Gastroenterology and Hepatology, 2008Co-Authors: Petros Ypsilantis, Ioannis Tentes, Maria Lambropoulou, Konstantinos Anagnostopoulos, Nikolaos Papadopoulos, Alexandros Kortsaris, Constantinos SimopoulosAbstract:Background and Aim: Mesna (2-mercaptoethane-sulfonate) has been shown to attenuate oxidative injury induced by ischemia reperfusion (I/R) in the kidneys, the liver, and the intestine; however, its mechanism of action has not been fully elucidated. We sought to determine a prophylactic admininstration schedule of Mesna that would confer optimal antioxidant protection on the intestinal mucosa following I/R and to investigate whether Mesna's action is mediated via inhibition of nuclear factor-κB (NF-κB) activity. Methods: Wistar rats were subjected to one of the following: (a) induction of 30 min ischemia followed by 60 min reperfusion (I30/R60) of the intestine, (b) pretreatment with intraperitoneal or oral Mesna at various time- and dose- administration schedules plus I30/R60, (c) sham operation, (d) no operation (controls), or (e) oral Mesna alone. At the end of the reperfusion period or at various time points after Mesna alone administration, the oxidative state of the intestinal mucosa was assessed in terms of glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity. In addition, NF-κB activity in the intestinal mucosa was assessed immunohistochemically in the oral Mesna plus I/R and in the oral Mesna alone groups. Results: Sham operation caused mild stress, while I/R caused substantial oxidative stress in the intestinal mucosa. Mesna pretreatment had an antioxidant effect which varied from attenuation to prevention of oxidative stress. Over the two routes of administration, the oral proved to be more effective and had a time- and dose- dependent effect. The antioxidant action of Mesna was not related to enhancement of the intestinal mucosa oxidative state. Furthermore, I/R induced NF-κB activation in the intestinal mucosa which was inhibited by Mesna pretreatment. In the absence of oxidative damage, Mesna led to downregulation of activated NF-κB. Conclusions: Prophylaxis with Mesna prevents oxidative stress induced by I/R in the intestine via inhibition of NF-κB activation.
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Mesna protects intestinal mucosa from ischemia reperfusion injury
Journal of Surgical Research, 2006Co-Authors: Petros Ypsilantis, Ioannis Tentes, Maria Lambropoulou, Nikolaos Papadopoulos, Alexandros Kortsaris, Constantinos SimopoulosAbstract:Background Mesna is a thiol used for the prevention of oxazaphosphorine-induced hemorrhagic cystitis. However, its antioxidant properties on renal and hepatorenal oxidative damage, as well as its mucoprotective effect on the intestinal epithelium have also been shown. The aim of this study was to investigate the potential beneficial effect of Mesna on ischemia/reperfusion (I/R)-induced oxidant damage of the intestinal mucosa. Materials and methods Wistar rats were subjected to intestinal I/R for 30 min, induced by occlusion of the superior mesenteric artery, followed by 60 min reperfusion. Mesna was administered at 3 time points relative to ischemia; 60 min before ischemia, at the onset of ischemia or at the onset of reperfusion. At the end of the study period, jejunal segments were excised and assessed for histopathologic score, apoptotic index using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) assay and glutathione/glutathione disulfide (GSH/GSSG) ratio, as a marker of oxidative stress. Results I/R caused deterioration of histological characteristics and induction of apoptosis and oxidative stress in the intestinal mucosa. Changes regarding histology and apoptosis were prevented when Mesna was administered 60 min before ischemia, but were attenuated when Mesna was administered at the onset of ischemia or reperfusion. In all Mesna groups, oxidative stress was reduced. Conclusions Mesna can ameliorate or even prevent intestinal I/R injury by reducing oxidative stress.
