mesna and Reperfusion-Injury

The lung is severely affected by intestinal ischemia-reperfusion (I-R) injury. Mesna, a thiol compound, possess anti-inflammatory and antioxidant properties. We aimed in the present work to explore the potential beneficial effects of Mesna on the acute lung damage mediated by intestinal I-R in a rat model. Forty male adult albino rats were randomly separated into; control, intestinal I-R, Mesna I and Mesna II groups. Mesna was administered by intraperitoneal injection at a dose of 100 mg/kg, 60 min before ischemia (Mesna I) and after reperfusion (Mesna II). Arterial blood gases and total proteins in bronchoalveolar lavage (BAL) were measured. Lung tissue homogenates were utilized for biochemical assays of proinflammatory cytokines and oxidative stress markers. Lung specimens were managed for examination by light and electron microscopy. Our results revealed that Mesna attenuated the histopathological changes and apoptosis of the lung following intestinal I-R. Mesna also recovered systemic oxygenation. Mesna suppressed neutrophil infiltration (as endorsed by the reduction in MPO level), reduced ICAM-1 mRNA expression, inhibited NF-κB pathway and reduced the proinflammatory cytokines (TNF-α, IL-1β and IL-6) in the lung tissues. Mesna maintained the antioxidant profile as evidenced by the elevation of the tissue GPx and SOD and down-regulation of HSP70 immune-expressions. Accordingly, Mesna treatment can be a promising way to counteract remote injury of the lung resulted from intestinal I-R.

Topics: Acute Lung Injury; Animals; Antioxidants; Apoptosis; Cytokines; Down-Regulation; HSP72 Heat-Shock Proteins; Inflammation; Intercellular Adhesion Molecule-1; Intestines; Lung; Male; Malondialdehyde; Mesna; Neutrophil Infiltration; Oxidative Stress; Rats; Reperfusion Injury; RNA, Messenger

Although the precise mechanism by which ischemia/reperfusion injury occurs in the spinal cord remains unclear, it is evident that free oxygen radicals and apoptosis play major roles in the destruction of membrane lipids, damage to DNA and cell death. The apoptotic process involves activation of the caspase-3 cascade. Although it is widely used as a protective agent against cell injury, it is unknown whether mesna (2-mercaptoethane sulfonate) ameliorates neuronal ischemic injury. The aim of this study was to determine the effect of mesna on caspase-3 activity in a rabbit model. Adult rabbits underwent spinal cord ischemic injury via occlusion of the abdominal aorta for 20 min. Twenty-four hours after ischemia, spinal cord samples were obtained and tissue caspase-3 activity was measured. Rabbits that had been given a single dose of 150 mg/kg mesna had decreased caspase-3 activity in the spinal cord following ischemia/reperfusion injury, indicating a protective effect. However, caspase-3 activity was lower in rabbits given methylprednisolone than in those given mesna, indicating that methylprednisolone has the stronger protective effect of the two agents.

Topics: Animals; Apoptosis; Caspase 3; Female; Mesna; Methylprednisolone; Neuroprotective Agents; Rabbits; Reperfusion Injury; Spinal Cord Injuries; Spinal Cord Ischemia

We investigated the role of the prophylactic administration of the antioxidant 2-mercaptoethane sulfonate (mesna) on the hepatocyte-regenerating capacity following partial hepatectomy (PH) with concurrent Pringle maneuver.. Wistar rats were subjected to PH (70% hepatectomy), 30 min Pringle maneuver, PH plus Pringle with or without mesna pretreatment (400 mg/kg, per os, 3 h before Pringle), or sham operation. At 24 h, 48 h, 72 h, and 1 week after operation, relative liver weight, hepatocyte mitotic activity (mitotic index), the histopathological score and serum aspartate aminotransferase, and alanine aminotransferase concentrations were assessed. At 1 h after operation, oxidative stress markers (glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity) and nuclear factor-kappaB (NF-kappaB) activity were assessed.. Hepatectomy stimulated the regenerating process and induced mild oxidative stress and the activation of NF-kappaB in hepatocytes, while causing tissue injury in the remnant liver. When PH was performed under Pringle maneuver, hepatocyte mitotic activity was substantially suppressed, although Pringle alone initiated a delayed regenerating response. Furthermore, Pringle maneuver deteriorated oxidative stress markers, markedly increased NF-kappaB activity, and aggravated tissue injury, as compared to hepatectomy alone. Mesna pretreatment prevented the Pringle-induced antimitotic effect and the induction of oxidative stress, inhibited the activation of NF-kappaB, while attenuating liver injury after PH under Pringle.. The excessive activation of NF-kappaB is related to the suppression of hepatocyte-regenerating activity following PH with concurrent liver ischemia. Mesna pretreatment protects the liver against the Pringle-induced antimitotic effect after PH via the prevention of oxidative stress and the inhibition of NF-kappaB activation.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Glutathione; Hepatectomy; Liver; Liver Regeneration; Malondialdehyde; Mesna; Mitotic Index; Models, Animal; NF-kappa B; Organ Size; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase; Time Factors

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 administration 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-kappaB (NF-kappaB) activity.. 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-kappaB activity in the intestinal mucosa was assessed immunohistochemically in the oral mesna plus I/R and in the oral mesna alone groups.. 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-kappaB activation in the intestinal mucosa which was inhibited by mesna pretreatment. In the absence of oxidative damage, mesna led to downregulation of activated NF-kappaB.. Prophylaxis with mesna prevents oxidative stress induced by I/R in the intestine via inhibition of NF-kappaB activation.

Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Down-Regulation; Glutathione Disulfide; Immunohistochemistry; Injections, Intraperitoneal; Intestinal Mucosa; Intestines; Malondialdehyde; Mesna; NF-kappa B; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase; Time Factors

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.. 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.. 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.. Mesna can ameliorate or even prevent intestinal I/R injury by reducing oxidative stress.

Topics: Animals; Antioxidants; Apoptosis; Constriction; Glutathione; In Situ Nick-End Labeling; Intestinal Mucosa; Jejunum; Mesenteric Artery, Superior; Mesna; Oxidation-Reduction; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury

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.. Wistar albino rats were subjected to 45-min hepatic ischemia, followed by 60-min reperfusion. 2-Mercaptoethane sulfonate, 150 mg/kg, or saline was given intraperitoneally (i.p.) twice, 15 min before ischemia and immediately before reperfusioin. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels to assess liver function. Liver tissue samples were taken to measure the levels of malondialdehyde (MDA), an end-product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. We also measured hepatic collagen content, as a fibrosis marker.. Plasma ALT and AST levels were higher in the I/R group than in the control group, but this increase was significantly decreased by MESNA treatment. Hepatic GSH levels, which were significantly depressed by I/R, increased back to the control levels in the MESNA-treated I/R group. Increases in tissue MDA levels and MPO activity caused by I/R injury decreased back to the control levels after MESNA treatment. Similarly, the increased hepatic collagen content in the I/R group decreased to the level of the control group after MESNA treatment.. The fact that MESNA alleviated I/R-induced injury of the liver and improved hepatic structure and function suggests that its antioxidant and oxidant scavenging properties may be of therapeutic value in protecting the liver against oxidative injury caused by I/R.

Topics: Animals; Free Radical Scavengers; Liver Diseases; Male; Mesna; Models, Animal; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury

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.

Topics: Animals; Collagen; Creatinine; Free Radicals; Glutathione; Kidney; Kidney Function Tests; Male; Malondialdehyde; Mesna; Nitroblue Tetrazolium; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury