Attenuated mild colonic inflammation and improved survival from severe DSS-colitis of transgenic Cu/Zn-SOD mice

Mucosal tissue damage in chronic inflammatory bowel disease (IBD) is partly caused by an enduring exposure to excessive amounts of reactive oxygen metabolites (ROM). To protect themselves from the toxic effects of ROM, most intestinal cell types constitutively express the highly specific, key ROM-neutralizing cytosolic enzyme Cu/Zn-superoxide dismutase (SOD). Under inflammatory conditions, however, its protein and activity levels have consistently been reported as being decreased. To elucidate a direct functional relationship between intracellular Cu/Zn-SOD expression and intestinal inflammation, we investigated the effects of transgenic human Cu/Zn-SOD overexpression in acute and chronic murine dextran sodium sulfate (DSS)-induced colitis. When subjected to a mild form of acute colitis, the Cu/Zn-SOD overexpressing mice showed a significantly lower colonic activity of neutrophilic myeloperoxidase (MPO) than their nontransgenic littermates. This difference was particularly evident in the male animals. In contrast, a severe acute colitis did not lead to any differences in MPO activity between both groups. Yet, when the animals were subsequently allowed to recover, MPO levels were again significantly lower in the transgenes, suggesting an involvement of Cu/Zn-SOD in, particularly, the clearance of neutrophils. Specific, immunohistochemical identification of neutrophils confirmed the validity of the MPO activity measurements. In addition, transgenic animals showed a remarkable survival benefit from severe DSS colitis over their nontransgenic littermates, particularly during or shortly after the acute inflammatory phase. During the chronic inflammatory phase, which was not characterized by massive neutrophil infiltration, no effects of Cu/Zn-SOD overexpression were noted. Paradoxically, overexpression of Cu/Zn-SOD did not obviously improve the colitis-related (oxidative) injury or symptoms at any stage of the experiment. Surprisingly, however, we did observe a pronounced male gender preference for DSS susceptibility that was reflected by increased male colitis mortality. Our findings provide direct in vivo evidence for a protective, neutrophil-related role for Cu/Zn-SOD in intestinal inflammation. As such, they support the concept of SOD-based (adjunct) antioxidant treatment strategies for inflammatory bowel disease.     

Melatonin and N-acetylcysteine have beneficial effects during hepatic ischemia and reperfusion

This study was designed to study the effects of Melatonin (Mel) and N-Acetylcystein (NAC) on hepatic ischemia/reperfusion (I/R) injury in rats. For this purpose Wistar albino rats were subjected to 45 minutes of hepatic ischemia followed by 60 minutes of reperfusion period. Melatonin (10 mg/kg) or NAC (150 mg/kg) were administered alone or in combination, intraperitoneally, 15 minutes prior to ischemia and just before reperfusion. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Liver tissues were taken for determination of malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; protein carbonyl concentration (protein oxidation) (PO), a specific marker of oxidative damage of proteins; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Plasma ALT and AST activities were higher in ischemia/reperfusion group than in control. They were decreased in the groups given Mel, NAC or the combination. Hepatic GSH levels, significantly depressed by I/R, were elevated to control levels in the combination group, whereas treatment with Mel or NAC alone provided only a limited protection. Hepatic MDA and PO levels, and MPO activity were significantly increased by I/R. The increase in these parameters were partially decreased by Mel or NAC alone, whereas treatment with the combination reduced these values back to control levels. In conclusion, considering the dosages used, Mel appeared to be significantly more potent than NAC in reversing the oxidative damage induced by I/R. Our findings show that Mel and NAC have beneficial effects against the I/R injury and due to their synergistic effects, when administered in combination, may have a more pronounced protective effects on the liver.     

Effect of copper- and zinc-methionine supplementation on bioavailability,mineral status and tissue concentrations of copper and zinc in ewes

The effect of feeding Cu- and Zn-methionine to ewes was studied in a 240d feeding trial. The plasma and tissue Cu and Zn concentrations and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) activity were employed to assess the relative bioavailability from Cu- and Zn-methionine. The macro and micronutrient intake, utilization, plasma mineral status, tissue accumulation of Cu and Zn as well as wool concentration of Cu and Zn were studied in ewes (n=12) fed a corn-soybean meal based basal diet with 50% more Cu and Zn supplementation over the basal diet either from Cu- and Zn-sulfate (Cu-Sulf+Zn-Sulf group) or Cu- and Zn-methionine (Cu-Meth+Zn-Meth group). The average daily feed intake and body weight gain of ewes did not differ due to dietary supplementation of Cu- and Zn-methionine. However, dry matter intake was comparatively lower and thus resulted in better feed: gain in Cu- and Zn-methionine group as compared to ewes fed Cu- and Zn-sulfate. Supplementation of Cu and Zn over the basal diet either from methionine-chelated or sulfate sources resulted in increased plasma Cu and Zn as well as Cu/Zn-SOD activity on d-30, which indicated a positive correlation between plasma Cu and Zn and Cu/Zn-SOD activity. The gut absorption, liver concentrations of Cu and Zn, and liver Cu/Zn-SOD activity were significantly (P<0.01) higher in ewes supplemented with Cu- and Zn-methionine compared to Cu- and Zn-sulfate. Periodical analysis of wool samples indicated no significant difference in Cu and Zn content between Cu-and Zn-methionine and Cu- and Zn-sulfate groups. Feeding of Cu and Zn from methionine-chelated source resulted in reduced (P<0.01) excretion of Cu and Zn in feces indicating their better utilization, and this will have positive implication on environment. The gut absorption values, plasma and liver tissue concentrations of Cu and Zn supported the hypothesis that Cu- and Zn-methionine supplements have better bioavailability compared to Cu- and Zn-sulfate and Cu- and Zn-dependent enzyme (Cu/Zn-SOD) could be used to determine the bioavailability of Cu and Zn.     

Pulmonary protective effects of hyberbaric oxygen and N-acetylcysteine treatment in necrotizing pancreatitis

The purpose of this study is to analyze the protective effect of combining N-acetylcysteine (NAC) and hyberbaric oxygen (HBO) treatment in the lung tissue during acute pancreatitis. Sixty Sprague-Dawley male rats were randomly divided into five groups; Group I; Control group (n=12), Group II; pancreatitis group (n=12), Group III; pancreatitis + NAC treatment group (n=12), Group IV; pancreatitis + HBO treatment group (n=12), Group V; pancreatitis + HBO + NAC treatment group (n=12). HBO was applied postoperatively for 5 days, twice a day at 2.5 fold absolute atmospheric pressure for 90 min. Lung tissue was obtained for measuring malondialdehyde (MDA), superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GSH-Px) levels along with histopathological tissue examinations. This study showed that all three treated groups (HBO alone, NAC alone and combined HBO+NAC treatment) had pulmonary protective effects during acute necrotizing pancreatitis.     

Oxidative stress in the brain tissue of laboratory mice with acute post insulin hypoglycemia

Malondialdehyde (MDA), Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and selenium-dependent glutathione peroxidase (GSPHx) are currently considered to be basic markers of oxidative stress. MDA is one of the end-products of the peroxidation of membrane lipids, whereas enzymes Cu,Zn-SOD and GSHPx belong to the natural antioxidants. The role of oxygen free radicals in the pathogenesis of many diseases is well documented. The aim of this study was to ascertain the influence of insulin-induced acute hypoglycemia on oxidative stress in the brain tissue. Hypoglycemia was induced in ICR mice by intraperitoneal administration of insulin at a dose 24 IU/kg. There was a correlation between the severity of hypoglycemia and the levels of MDA, Cu,Zn-SOD and GSHPx. The results showed that in severe hypoglycemia (serum glucose concentration below 1.0 mmol/l) the lipoperoxidation in brain tissue expressed as the level of MDA was higher in comparison with normoglycemic controls (glycemia around 3.7 mmol/l) as well as in comparison with the levels of MDA during moderate hypoglycemia (glycemia ranging between 1-2 mmol/l). This indicates the enhancement of lipoperoxidation in the brain tissue during severe hypoglycemia. However, both enzymes - Cu,Zn-SOD or GSHPx - did not show a similar tendency.     

Modulating effect of Hesperidin on experimental murine colitis induced by dextran sulfate sodium

Hesperidin, a flavanone-type flavonoid, is abundant in citrus fruit and has a wide range of pharmacological effects. Here we investigated the effect of Hesperidin on dextran sulphate sodium (DSS)-induced experimental ulcerative colitis in mice. Sulfasalazine (positive control) and Hesperidin in doses of 10, 40 and 80 mg/kg were administered orally once a day for 7 days, beginning concurrently with exposure to DSS. The symptom of ulcerative colitis was evaluated by disease activity index (DAI) and the wet weight of colon. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content and the levels of interleukin-4 (IL-4) and interleukin-6 (IL-6) in serum were measured to observe the possible mechanisms. Oral administration of Hesperidin significantly decreased DAI, MPO activity, MDA content and the level of IL-6 in serum (p<0.01), while there was no significantly effect on the level of IL-4 in serum. These results demonstrate that Hesperidin can ameliorate DSS-induced experimental colitis, and may be useful in the prevention and treatment of colitis.     

Effect of the new thiazolidinedione-pioglitazone on the development of oxidative stress in liver and kidney of diabetic rabbits

Impaired homeostasis under diabetic conditions is connected with the increased production of free radicals and deficiency of antioxidative systems. The aim of this study was to analyze the effect of new oral antidiabetic drug-pioglitazone on activity of antioxidant factors and lipid peroxidation in vivo. The liver and kidney of alloxan-induced diabetic rabbits were examined after 4 and 8 weeks of treatment. After 4 weeks of diabetes the superoxide dismutase (Cu,Zn-SOD) activity in the liver was diminished while the catalase (CAT) activity and the level of ascorbic acid (AA) were elevated in comparison with the control group. Pioglitazone treatment during 4 weeks decreased the catalase activity in relation to the control diabetic animals. After 8 weeks of diabetes the CAT activity in the liver was elevated in comparison with the control group. Pioglitazone treatment during 8 weeks decreased the CAT activity and the level of lipid peroxidation products (LPO), and increased the Cu,Zn-SOD activity in relation to control diabetic animals. After 4 weeks of diabetes in the kidney the Cu,Zn-SOD activity and the level of ascorbic acid (AA) were diminished while the CAT activity and the LPO level were elevated in comparison with the control group. Pioglitazone treatment during 4 weeks increased the AA and decreased the LPO levels in relation to non-treated diabetic animals. After 8 weeks of disease the Cu,Zn-SOD activity in the kidney was diminished in comparison with the control group. Pioglitazone during 8 weeks decreased the LPO level in relation to non-treated diabetic animals. This study shows that diabetic animals undergo an important oxidative stress, which is partially corrected by pioglitazone treatment.     

Specific induction of metallothionein synthesis by mitochondrial oxidative stress.

Metallothionein (MT), a sulfhydryl-rich protein, may be increased by administration of a variety of agents, including metals, cytokines and oxidative stress agents. Mitochondria are a major source of reactive oxygen species, but antioxidant systems against mitochondrial free radicals are not fully understood. In this study, we examined the induction of MT synthesis by administration of mitochondrial-specific reactive oxygen generators such as antimycin A (AA), an electron transfer inhibitor, and 2,4-dinitrophenol (DNP), an uncoupling agent. Subcutaneous administration of AA to mice significantly increased the hepatic MT concentration in a dose- and time-dependent manner. AA slightly elevated glutathione peroxidase (GSHPx) activity, but the rate of increase in GSHPx (1.3-fold) was smaller than that in MT (11.8-fold). Other antioxidants such as catalase, manganese-superoxide dismutase (Mn-SOD), copper/zinc-superoxide dismutase (Cu/Zn-SOD) and GSHPx were not activated by AA treatment. Moreover, administration of DNP induced the synthesis of MT in the liver. Although DNP slightly elevated Mn-SOD activity, the rate of increase in Mn-SOD (1.3-fold) was smaller than that in MT (3.7-fold). Other antioxidants such as catalase, Cu/Zn-SOD and GSHPx were not activated by DNP treatment. These data suggest that MT plays a major role in protection against oxidative stress induced in mitochondria.     

Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism

Oxytocin (OT), a nonapeptide produced in the paraventricular and the supraoptical nuclei in the hypothalamus has a wide range of effects in the body. However, the role of OT on the gastrointestinal (GI) tract has to be settled. OT may participate in the regulation of motility, secretion, blood flow, cell turnover and release of neurotransmitters and/or peptides in the GI tract, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in the modulation of immune and inflammatory processes. The present work was conducted to assess the possible therapeutic effects of OT against the acetic acid-induced colonic injury in the rat. METHODS: Colitis was induced by intracolonic administration of acetic acid (5%) in Sprague-Dawley rats (200-250 g). Either saline or OT (0.5 mg/kg) was injected subcutaneously, immediately after the induction of colitis and repeated two times a day for 4 days. On the 4th day, rats were decapitated and distal 8 cm of the colon were removed for the macroscopic and microscopic damage scoring, determination of tissue wet weight index (WI), malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Colonic collagen content, as a fibrosis marker was also determined. Lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) levels were assayed in serum samples. In the acetic acid-induced colitis, macroscopic and microscopic damage scores, WI, MDA and MPO levels were significantly increased, while GSH levels were decreased when compared to control group (p <0.05-<0.001). Treatment with OT abolished the colitis-induced elevations in damage scores, WI, MDA and MPO levels and restored the GSH levels (p <0.05-0.001). Similarly, acetic acid increased the collagen content of colonic tissues and OT-treatment reduced this value to the level of the control group. Serum LDH and TNF-alpha levels were also elevated in the acetic acid-induced colitis group as compared to control group, while this increase was significantly decreased by OT treatment. The results suggest that OT, which improves the antioxidative state of the colonic tissue and ameliorates oxidative colonic injury via a neutrophil-dependent mechanism, requires further investigation as a potential therapeutic agent in colonic inflammation.     

The effect of hyperbaric oxygen treatment on oxidative stress in experimental acute necrotizing pancreatitis

Various protocols may be used for acute pancreatitis treatment. Recently, the benefit of hyperbaric oxygen (HBO) has been demonstrated. To clarify the mechanism of HBO on the process of the acute pancreatitis, we determined the levels of antioxidant enzymes in an acute pancreatitis model. Forty-five Sprague-Dawley rats were randomly divided into three groups: Group I: sham group (n=15), Group II: pancreatitis group (n=15), Group III: pancreatitis group undergoing HBO therapy (n=15). HBO was applied postoperatively for 5 days, two sessions per day at 2.5 fold absolute atmospheric pressure (ATA) for 90 min. Superoxide dismutase (Cu/Zn-SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH Px) activity were measured in pancreatic tissue and erythrocyte lysate. MDA and GSH Px were also determined in plasma. In addition, amylase levels were measured in the serum. While serum amylase levels and MDA values in erythrocyte, plasma and pancreatic tissue were decreased, the levels of GSH Px and SOD were found to be significantly increased in the Group III as compared to those of the Group II. The findings of our study suggest that HBO has beneficial effects on the course of acute pancreatitis and this effect may occur through the antioxidant systems.     

Trace element concentrations and superoxide dismutase and catalase activities in benign and malignant larynx tumors

The plasma and erythrocyte levels of zinc, copper, and magnesium and the activities of red-cell copper-zinc superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) were determined in patients with benign and malignant tumors of the larynx. Blood samples from patients and healthy controls were drawn using heparinized tubes. The erythrocyte Cu/Zn-SOD and CAT activities were determined spectrophotometrically and the zinc, copper, and magnesium concentrations were determined in erythrocyte and plasma by atomic absorption spectrometry. Variance analysis was employed in the statistical evaluation of the findings. There was a significant increase in red-cell Cu/Zn-SOD activity in the subjects with malignant and benign tumors compared to controls (p<0.001). The CAT activity increased only in the benign tumor group (p<0.01). The plasma zinc concentrations were significantly lower in the malignant tumor group (p<0.05) and significantly higher in the benign tumor group (p<0.01). The erythrocyte copper concentrations were significantly lower in both benign and malignant tumor groups (p<0.001). The plasma copper and magnesium and the erythrocyte magnesium concentrations did not show significant differences relative to controls (p>0.05). The increases in the activities of SOD and CAT activities and the changes in trace elements concentrations can indicate the presence of increased reactive oxygen species that might play a part in the pathogenesis larynx tumors. Presented at the IX Asian-Pacific Congress of Clinical Biochemistry, March 9–14, 2002, New Delhi, India.     

Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation

Acute inflammation is a common feature of many life-threatening pathologies, including septic shock. One hallmark of acute inflammation is the peroxidation of polyunsaturated fatty acids forming bioactive products that regulate inflammation. Myeloperoxidase (MPO) is an abundant phagocyte-derived hemoprotein released during phagocyte activation. Here, we investigated the role of MPO in modulating biologically active arachidonic acid (AA) and linoleic acid (LA) metabolites during acute inflammation. Wild-type and MPO-knockout (KO) mice were exposed to intraperitoneally injected endotoxin for 24 h, and plasma LA and AA oxidation products were comprehensively analyzed using a liquid chromatography–mass spectrometry method. Compared to wild-type mice, MPO-KO mice had significantly lower plasma levels of LA epoxides and corresponding LA- and AA-derived fatty acid diols. AA and LA hydroxy intermediates (hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids) were also significantly lower in MPO-KO mice. Conversely, MPO-deficient mice had significantly higher plasma levels of cysteinyl-leukotrienes with well-known proinflammatory properties. In vitro experiments revealed significantly lower amounts of AA and LA epoxides, LA- and AA-derived fatty acid diols, and AA and LA hydroxy intermediates in stimulated polymorphonuclear neutrophils isolated from MPO-KO mice. Our results demonstrate that MPO modulates the balance of pro- and anti-inflammatory lipid mediators during acute inflammation and, in this way, may control acute inflammatory diseases.     

Alterations of trace elements (Zn, Se, Cu, Fe) and related metalloenzymes in rabbit blood after severe trauma

To investigate the status of the trace elements (TEs) and related metalloenzymes activities in the injury and repair process after severe trauma, we established a rabbit model of severe trauma whose Injury Severity Score (ISS) was 22. Concentrations of blood selenium (Se) and serum copper (Cu), zinc (Zn), iron (Fe), and ferritin were measured on D0 (before injury), and day (D) 1, D2, D3, D6, D9, D14, D21, D28 after trauma, respectively. The activities of glutathione peroxidase (GPx), Cu/Zn superoxide dismutase (Cu/Zn-SOD), myeloperoxidase (MPO), the contents of lipid peroxidation product malondialdehyde (MDA) and serum biochemical profile were detected synchronously. In addition, the morphologic changes of major organs were observed at different time intervals. Results showed that blood Se and serum Zn, Fe contents decreased significantly within 2 weeks after injury. Serum Cu concentration was significantly reduced on D1 but normalized quickly. Serum ferritin level increased during the first week while following an obvious decrease thereafter. The blood GPx activity dropped markedly from D1 to D6, the serum Cu/Zn-SOD activity decreased on D1 and then increased significantly within 2 weeks, and the blood MPO-positive stained cells increased within a week after trauma and followed by a decrease from D14 to D21. The serum MDA increased significantly on D6. Seven of 34 rabbits died in 4-6 days after injury. Biochemistry values and pathological features revealed these rabbits died of multiple organ dysfunction syndrome (MODS). Our experiment suggested that the circulating TEs status is dramatically modified in response to trauma, which might be a factor in MODS.     

Combined Effects of Muscular Dystrophy,Ecological Stress,and Selenium on Blood Antioxidant Status in Broiler Chickens

The results obtained in this study demonstrated that experimentally induced alimentary muscular dystrophy (MD) in Cobb 500 broiler chickens resulted in increased plasma concentrations of malondialdehyde (MDA), deviations in activities of erythrocyte antioxidant enzymes Cu,Zn-SOD (decrease), and CAT (increase) as well as reduction in plasma concentrations of trace elements Cu, Zn, and Se in affected birds. These data evidenced the presence of oxidative stress in birds with MD, reared both under conditions of ecological comfort and ecological stress. The increased MDA and САТ levels and the reduced Cu,Zn-SOD, Cu, Zn, and Se concentrations in healthy chickens reared under unfavorable microclimatic conditions such as higher air temperature and humidity, higher ammonia concentrations, and lower light intensity were indicative about an induced ecological stress. After the 10-day oral treatment with a selenium-containing preparation, the levels of MDA, Cu,Zn-SOD, CAT, Cu, Zn, and Se attained their normal values in chickens with MD, reared under ecologically comfortable conditions. According to our results, ecological stress was shown to exert independently a significant adverse effect upon the levels of the studied parameters and possibly to be a cause for their slower and not complete normalization despite the selenium therapy in experimental broiler chickens.     

Modification of cardiac oxidative stress in alloxan-induced diabetic rabbits with repaglinide treatment

The aim of this study was to analyze the antioxidative effect of repaglinide in the heart of alloxan-induced diabetic rabbits. The activities of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), products of lipid peroxidation (LPO) and protein carbonyl groups (PCG) were estimated after 4 and 8 weeks of repaglinide treatment (1 mg daily). At significance level p<0.05, in diabetic heart the activities of Cu,Zn-SOD and CAT were elevated as compared to control values (by 60.7% and 55.3% for Cu,Zn-SOD, and by 89.7% and 77.4% for CAT after 4 and 8 weeks, respectively). The level of AA was diminished by 52.5% and 41.5% while GSH-Px and GSSG-R activities were decreased after 4 weeks of experiment (by 11.5% and 14.4%, respectively). GSH level was diminished by 33.2% after 8 weeks. Simultaneously, in diabetic heart the levels of LPO and PCG were elevated as compared to control values (by 51.6% and 111.3% for LPO, and by 72.0% and 132.9% for PCG after 4 and 8 weeks, respectively). In diabetic animals, repaglinide normalized GSH-Px activity and GSH level. It modified the activities of Cu,Zn-SOD, CAT and AA as compared to diabetic non-treated animals. In diabetic-treated rabbits the level of LPO was diminished as compared to diabetic non-treated animals, while the level of PCG was not affected. In the present study, repaglinide did not affect blood glucose and plasma insulin concentrations in diabetic rabbits. Nevertheless, the drug showed some beneficial antioxidative properties in the heart tissue.     

Investigation of the relationship between GSTM1 gene variations and serum trace elements,plasma malondialdehyde levels in patients with colorectal cancer

Background

The aim of this study is to investigate of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patient with colorectal cancer.

Mateials and Methods.

Genotype distributions of GSTM1 gene variations were determined using real-time polymerase chain reaction method. Serum trace element levels were determined using atomic absorption spectrophotometer method and plasma MDA levels were measurement by spectrophotometric method.

Results

Serum Cu levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GA heterozygous genotype of the GSTM1 (rs 112,778,559) gene variation compared to healthy controls (p?<?0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in patients carrying GG homozygous genotype of the GSTM1 (rs 112778559) gene variation compared to healthy controls carrying same genotype (p?<?0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GG homozygous genotype of the GSTM1 (rs 12068997) gene variation compared to healthy controls (p?<?0.05). On the other hand, serum Se levels were detected significantly lower in CRC patients carrying GA heterozygous and GG homozygous genotypes for GSTM1 (rs 112,778,559) and (rs 12,068,997) gene variations compared to healthy controls (p?<?0.05).

Conclusion

In our study, the evaluation of serum Cu, Zn and Se trace element levels and plasma MDA levels according to GSTM1 gene variations genotype distributions were enabled to obtain important biomarkers in terms of CRC development and progression.

     

Protective Effects of Erdosteine and Vitamins C and E Combination on Ischemia–Reperfusion-Induced Lung Oxidative Stress and Plasma Copper and Zinc Levels in a Rat Hind Limb Model

The aim of this study was to investigate the protective effects of erdosteine and vitamins C and E (VCE) on the lungs after performing hind limb ischemia–reperfusion (I/R) by assessing oxidative stress, plasma copper (Cu), and zinc (Zn) analysis. The animals were divided randomly into four groups as nine rats each as follows: control, I/R, I/R plus erdosteine, and I/R plus VCE combination. I/R period for 60 min was performed on the both hind limbs of all the rats in the groups of I/R, erdosteine with I/R, VCE with I/R allowing 120 min of reperfusion. The animals received orally erdosteine one time in a day and 3 days before I/R in the erdosteine group. In the VCE group, the animals VCE combination received one time in a day and 3 days before I/R, although placebo was given to control and I/R group animals. Lung lipid peroxidation (malondialdehyde [MDA]) level, superoxide dismutase (SOD), and catalase activities were increased, although lung glutathione (GSH) and plasma Zn levels decreased in I/R group in lung tissue compared with the control group. Serum MDA level, creatine kinase, and lactate dehydrogenase activities were increased in I/R group compared with the control. Lung MDA and plasma Zn levels and lung SOD activity were decreased by erdosteine administration, whereas lung GSH levels after I/R increased. The plasma Zn levels and lung SOD activity were decreased by VCE administration, although the plasma Cu and lung GSH levels increased after I/R. In conclusion, erdosteine has an antioxidant role on the values in the rat model, and it has more protective affect than in VCE in attenuating I/R-induced lung injury in rats.     

缺血预处理对肢体缺血/再灌注大鼠胃粘膜损伤的保护效应

目的：观察肢体缺血再灌注（LI／R）对胃粘膜的损伤作用及缺血预处理对其影响,探讨胃粘膜损伤的机制及缺血预处理（IPC）的作用机理。方法：观察并测定肢体缺血4h再灌注4h后以及应用肢体缺血预处理干预后各组胃粘膜损伤指数,胃结合粘液量;检测胃粘膜中髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）、丙二醛（MDA）、黄嘌呤氧化酶（XOD）含量的变化以及血浆中乳酸脱氢酶（LDH）的含量变化。结果：大鼠LI／R后胃粘膜损伤指数增加;胃结合粘液量较对照组显著下降;胃粘膜中MPO、MDA、XOD的值均较对照组增加,血浆中LDH的含量亦较对照组显著增加,胃粘膜组织中SOD的酶活力下降;IPC组与LIR组对比,胃结合粘液量较LIR组显著增加：胃粘膜损伤指数、胃粘膜中MPO的含量、以及胃粘膜中MDA、XOD、LDH均较LI／R组明显降低;胃粘膜中SOD酶活力增强。结论：LI／R作为应激原可引起胃粘膜损伤,导致应激性溃疡的发生;自由基在肢体缺血再／灌注后继发胃粘膜损伤过程中发挥作用。缺血预处理可减轻肢体缺血再灌注后的胃粘膜损伤,其作用机制可能是通过减少自由基的产生而发挥其保护作用。     

The pathogenesis of L-arginine-induced acute necrotizing pancreatitis: inflammatory mediators and endogenous cholecystokinin.

This study was aimed at an assessment of the role of oxygen-derived free radicals, cytokines and endogenous cholecystokinin (CCK) in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat. We measured the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn- and Cu, Zn-SOD) in pancreatic tissue, the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and CCK, and evaluated the protective effect of the xanthine oxidase inhibitor allopurinol and a novel CCK receptor antagonist KSG-504. Acute pancreatitis was induced in male Wistar rats by injecting 2x 250 mg/100 g body weight of Arg intraperitoneally in an 1-h interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. 200 mg x kg(-1) allopurinol 30 min before the first Arg treatment or 50 mg x kg(-1) KSG-504 30 min before and 6, 18 and 36 h after the first Arg injection was administered subcutaneously. Rats were killed at 6, 12, 24 and 48 h following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 h after the Arg injection (30,800 +/- 3,813 versus 6,382 +/- 184 U x L(-1) in the control) and normalized at 48 h. The tissue concentration of MDA was significantly elevated at 24 h, and reached the peak value at 48 h (5.00 +/- 1.75 versus 0.28 +/- 0.05 nM x mg(-1) protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 h, and the Cu, Zn-SOD activity was significantly lower at 12 h after the Arg injection as compared with the controls. Both the TNF-alpha and the IL-6 levels were already elevated significantly at 12 h and peak at 24 h versus the controls (19.1 +/- 7.9 U x mL(-1) and 57.6 +/- 11.2 pg x mL(-1) versus 3.1 +/- 0.8 U x mL(-1) and 15.2 +/- 3.1 pg x mL(-1), respectively). No significant changes in plasma CCK levels were observed. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 +/- 2.257 U x L(-1) at 24 h), prevented the increase in tissue MDA concentration (0.55 +/- 0.09 nM x mg(-1) protein at 48 h) and significantly ameliorated the pancreatic edema, necrosis and inflammation at 48 h after Arg administration. KSG-504 administration did not exert any beneficial effect on the development of histopathological changes neither modified the serum amylase or cytokine levels. Oxygen-derived free radicals and cytokines are involved, while endogenous CCK does not seem to play a role in the pathogenesis of Arg-induced acute pancreatitis.