Postnatal surgery for myelomeningocele in neonates: neurodevelopmental outcomes.

BACKGROUND: The study aims to evaluate the neurodevelopmental outcomes of neonates with myelomeningocele (MMC) operated in the postnatal period. METHODS: This is a prospective follow-up study in a tertiary neonatal intensive care unit. Neurodevelopmental outcomes of term neonates operated for MMC and healthy term newborns were compared with the Bayley Scales of Infant and Toddler Development -Third Edition (BSID III) at 12-18 months. RESULTS: A total of 57 cases were included in the study (patient group = 27; control group = 30). Demographic data between the groups were similar. Cognitive, linguistic, and motor composite scores of the patient group were lower than those of the control group (p < 0.001). In the patient group, those who underwent ventriculoperitoneal shunt had lower cognitive, language and motor scores than those without shunt (p < 0.05). The cognitive, linguistic, and motor composite scores in the patient group who underwent surgery before 72 h were better than those who underwent surgery after 72 h. DISCUSSION: In our study, it was found that the neurodevelopmental prognosis of MMC cases requiring ventriculoperitoneal shunt in the postnatal period was significantly worse than those without shunt. It is the first study in which the neurodevelopment of patients with MMC who were operated in the postnatal period was evaluated with BSID III evaluated and delays in all areas were shown in cases with MMC compared to normal cases. Better neurodevelopmental outcomes in patients operated in the first 72 h suggest that early surgery will improve neurodevelopmental outcomes in patients with MMC.

Comparison of the neurocognitive outcomes in term infants treated with levetiracetam and phenobarbital monotherapy for neonatal clinical seizures.

PURPOSE: This study aims to compare the neurocognitive outcome in term infants who were treated using phenobarbital (PB) and levetiracetam (LEV) monotherapy for neonatal clinical seizures. METHODS: Term infants who were treated using PB or LEV monotherapy as the first-line anti-epileptic treatment for neonatal clinical seizures and followed-up in a pediatric neurology outpatient clinic were enrolled in this study. Neurodevelopmental outcome assessments were carried out using the Bayley Scales of Infant Development, third edition (BSID-III), including cognitive, receptive language, expressive language, fine motor and gross motor subscales. RESULTS: The study group consisted of 62 infants who received monotherapy with PB monotherapy (n = 22) and LEV (n = 40). The mean duration of monotherapy treatment was 8 ± 6 months. There was no statistically significant difference between PB and LEV monotherapy groups concerning each outcome parameter on the BSID-III. There was also no statistically significant difference between PB and LEV monotherapy subgroups excluding the infants with neurodevelopmental impairment with a BSID-III scale score<7 or a composite score<85. CONCLUSION: Our findings suggest that both LEV and PB therapy can be equally safe as monotherapy for neonatal clinical seizures for the neurodevelopmental outcome assessment with BSID-III.

Role of Oxidative Stress in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Objectives: To investigate the role of oxidative stress on pseudoexfoliation formation and progression from pseudoexfoliation syndrome (XFS) to pseudoexfoliation glaucoma (XFG). Materials and Methods: This study investigated oxidative stress biomarkers in blood samples from 58 patients with XFG, 47 patients with XFS, and 134 healthy age- and sex-matched controls. Results: The highest serum malondialdehyde (MDA) levels were measured in XFG patients (p<0.001), and MDA level was higher in XFS patients than controls (p<0.001). Superoxide dismutase (SOD) and catalase (CAT) enzyme activities were significantly lower in XFS and XFG patients than in the control group, whereas a significant increase was observed in glutathione (GSH) levels (p<0.001 for all). However, levels of these three biomarkers did not differ significantly between XFS and XFG patients (p=0.188, p=0.185, and p=0.733, respectively). Nitric oxide (NO) concentration was significantly lower in XFG patients compared to XFS patients and controls (p<0.001) but did not differ between XFS patients and controls (p=0.476). Conclusion: Elevated MDA levels suggest that lipid peroxidation is important in XFS and XFG development and progression from XFS to XFG. In addition, reduction in SOD and CAT enzyme activities is considered a deficiency in the enzymatic antioxidant protection system. Furthermore, GSH values may be evaluated as a compensatory response to oxidative stress in XFS and XFG. Alterations in NO indicate the role of a vascular regulatory factor in the progression from XFS to glaucoma.

Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome.

To the best of our knowledge, this is the first study concerning the effect of boric acid (BA) administration on fetal alcohol syndrome (FAS). In this study, the aim was to investigate prenatal alcohol-induced oxidative stress on the cerebral cortex of newborn rat pups and assess the protective and beneficial effects of BA supplementation on rats with FAS. Pregnant rats were divided into three groups, namely the control, alcohol and alcohol + boric acid groups. As markers of alcohol-induced oxidative stress in the cerebral cortex of the newborn pups, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were measured. Although the MDA levels in the alcohol group were significantly increased compared with those in the control group (P<0.05), the MDA level in the alcohol + boric acid group was shown to be significantly decreased compared with that in the alcohol group (P<0.01). The CAT activity of the alcohol + boric acid group was significantly higher than that in the alcohol group (P<0.05). The GPx activity in the alcohol group was decreased compared with that in the control group (P<0.05). These results demonstrate that alcohol is capable of triggering damage to membranes of the cerebral cortex of rat pups and BA could be influential in antioxidant mechanisms against oxidative stress resulting from prenatal alcohol exposure.

Antioxidant and anti-apoptotic activity of vasoactive intestinal peptide (VIP) against 6-hydroxy dopamine toxicity in the rat corpus striatum.

6-Hydroxydopamine (6-OHDA) is an oxidative stress neurotoxin, which is oxidized in neurons, causes respiratory inhibition, and induces free radical formation and oxidative stress. Therefore, a 6-OHDA-induced Parkinson's disease (PD) experimental model can be used to test a candidate molecule for use as an antioxidant that could be a promising therapeutic for treating Parkinson's disease. Recent studies have shown that vasoactive intestinal peptide (VIP) might be a good candidate agent for the treatment of PD. In this study, the anti-apoptotic and antioxidant actions of VIP were investigated using the 6-OHDA-lesioned rat model for PD. Twenty-four young adult Sprague-Dawley rats were used. The rats were separated into the following groups: group I (n = 8), sham operated; group II (n = 8), 6-OHDA lesioned; group III (n = 8), 6-OHDA lesioned + i.p. VIP-injected (25 ng/kg) every 2 days for 15 days. The first i.p. injection of VIP was made 1 h after the intrastriatal 6-OHDA microinjection. Antioxidant enzymatic activity [super oxide dismutase (SOD) and catalase (CAT)], lipid peroxidation, nitric oxide and DNA fragmentation were measured from homogenates isolated from the corpus striatum. SOD, CAT, malondialdehyde, and DNA fragmentation were measured using a spectrophotometer, and nitric oxide (NO) levels were measured by capillary electrophoresis. 6-OHDA significantly induced oxidative stress, lipid peroxidation, and DNA fragmentation in the corpus striatum of rats. VIP significantly protected neuronal tissue from oxidative stress and apoptosis by reducing lipid peroxidation and DNA fragmentation. 6-OHDA toxicity did not cause significant changes in NO production in the corpus striatum. However, VIP treatment significantly reduced NO levels in brain tissue.

Betaine (trimethylglycine) as a nutritional agent prevents oxidative stress after chronic ethanol consumption in pancreatic tissue of rats.

In this study, we investigated the free radical-mediated cytotoxic effects of chronic ethanol consumption on the pancreatic tissue and a possible cytoprotective effect of betaine as a methyl donor and an important participant in the methionine cycle. Twenty-four male Wistar rats were divided into control, ethanol, and ethanol+betaine groups. Prior to sacrifice, all groups were fed 60 mL/diet per day for two months. Rats in the ethanol group were fed with ethanol 8 g/kg/day. The ethanol+betaine groups were fed ethanol plus betaine (0.5 % w/v). Malondialdehyde levels and adenosine deaminase, superoxide dismutase, and xanthine oxidase activities were determined in pancreatic tissues of rats. Compared to control group, MDA levels increased significantly in the ethanol group (p<0.05). MDA levels in the ethanol+betaine group were significantly decreased compared to the ethanol group (p<0.05). ADA activity in the ethanol+betaine group decreased significantly when compared to the ethanol group (p<0.05). XO activities in ethanol-fed rats were decreased significantly compared to the control group (p<0.05). XO activity in the betaine group was increased significantly (p<0.05) compared to the ethanol group. SOD activity in the ethanol group decreased significantly compared to control group (p<0.001). SOD activity in the ethanol+betaine group decreased significantly (p<0.05) compared to the control group. We think that betaine, as a nutritional methylating agent, may be effective against ethanol-mediated oxidative stress in pancreatic tissue.

Effects of chronic ethanol consumption on brain synaptosomes and protective role of betaine.

To evaluate the cytotoxic effects of chronic ethanol consumption on brain cerebral synaptosomes and preventive role of betaine as a methyl donor and S-adenosylmethionine precursor, 24 male Wistar rats were divided into three groups: control, ethanol (8 g/kg/day) and ethanol plus betaine(0.5% w/v) group. Animals were fed 60 ml/diet per day for two months, then sacrificed. Malondialdehyde (MDA), protein carbonyl contents and adenosine deaminase (ADA) activities were determined in synaptosomal/mitochondrial enriched fraction isolated from rat cerebral cortexes. When compared to controls, ethanol containing diet significantly increased MDA levels (P < 0.05), also increased protein carbonyl levels and adenosine deaminase activities. But these were not statistically significant (P > 0.05). However, adding betaine to ethanol containing diet caused a significant decrease in MDA, protein carbonyl levels and adenosine deaminase activities (P < 0.05). These results indicate that betaine may appear as a protective nutritional agent against cytotoxic brain damage induced by chronic ethanol consumption.

Betaine prevents loss of sialic acid residues and peroxidative injury of erythrocyte membrane in ethanol-given rats.

To evaluate chronic ethanol toxicity on erythrocyte membrane and preventive action of betaine as a methyl donor, 24 male Wistar albino rats were divided into three groups: control, ethanol and ethanol plus betaine group. Animals were fed 60 ml diet per day for two months. Rats in the ethanol group were fed ethanol 8 g/kg/day. The ethanol + betaine groups were fed ethanol plus betaine (0.5% w/v). After two months, all animals were killed. Malondialdehyde (MDA) and sialic acid (SA) levels were determined in plasma samples. Osmotic fragility tests were performed on whole blood samples and erythrocyte membrane thiol contents were determined using membrane suspensions. Plasma MDA levels in ethanol-given rats were increased significantly compared to the control group of rats (p < 0.05). MDA in the betaine group was significantly lower than that in the ethanol group (p < 0.05). Erythrocyte membrane thiol contents in ethanol group were decreased compared with those of the control group (p < 0.05). Thiol contents were increased slightly after betaine therapy, but this increase was not statistically significant (p > 0.05). Plasma sialic acid levels in the ethanol group were significantly higher than in the control group (p < 0.05). Sialic acid was decreased in the betaine group compared to the ethanol group (p < 0.05). In the osmotic fragility test, we observed that chronic ethanol consumption increased erythrocyte hemolysis. Betaine protected against ethanol-induced hemolysis. Our findings show that chronic ethanol administration affects erythrocyte membrane properties and this may be related to oxidative stress. Betaine protects erythrocyte membrane alterations against chronic ethanol toxicity. Therefore betaine as a nutritional agent, may protect ethanol induced clinical problems associated with membrane abnormalities.

Effects of vitamin E and gemfibrozil on lipid profiles, lipid peroxidation and antioxidant status in the elderly and young hyperlipidemic subjects.

OBJECTIVE: This study has dealt with the effects of gemfibrozil and vitamin E (vit E) therapies on lipoprotein levels, lipid peroxidation and antioxidant statuses of the elderly and young hyperlipidemic subjects. METHODS: This study took place in the Internal Medicine Clinic, Faculty of Medicine, Osmangazi University, Turkey between 2004-2005. This study was carried out on 99 hyperlipidemic and 40 control subjects. Subjects were divided into 2 groups; elderly hyperlipidemic (n=65) and young hyperlipidemic (n=34). In the young and elderly hyperlipidemic subjects of the first group treated only with vit E (600 mg/day) for one month. In the young and elderly hyperlipidemic subjects of the second group were treated only with gemfibrozil (600 mg/twice daily) for one month. The 2 therapies of vit E and gemfibrozil were then combined and applied to the third group of our study. Reduced glutathione (GSH), glutathione peroxidase (GPx), total cholesterol (total chol), serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), vit E, malondialdehyde (MDA), superoxide dismutase (SOD) levels of the 3 groups were measured. RESULTS: In elderly hyperlipidemic therapy group: vit E groups, the post-treatment vit E levels increased. In the gemfibrozil groups, post-treatment TG level decreased whereas HDL level increased. In the vit E plus gemfibrozil groups, post-treatment TG level decreased, HDL, and vit E levels increased. In young hyperlipidemic therapy group: vit E groups, the post-treatment HDL, vit E, GSH, GPX levels increased whereas LDL, MDA, levels decreased. In the gemfibrozil groups, post-treatment TG, LDL decreased, HDL level increased. In the vit E plus gemfibrozil groups, post-treatment TG, LDL, MDA levels decreased whereas HDL, vit E, GSH levels increased. CONCLUSION: When combined, gemfibrozil and vit E are effective in preventing cardiovascular diseases.

Effect of quercetine and glutathione on the level of superoxide dismutase, catalase, malonyldialdehyde, blood pressure and neonatal outcome in a rat model of pre-eclampsia induced by NG-nitro-L-arginine-methyl ester.

OBJECTIVE: To anticipate the impact of antioxidant use on lipid peroxidation products, free oxygen radical scavengers, blood pressure (BP), proteinuria and neonatal outcome (as seen in percentage survival, litter birth weight) in a rat model of pre-eclampsia induced by NG-nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of nitric oxide synthase (NOS). MATERIAL AND METHODS: Female adult non-pregnant Sprague-Dawley rats (n=40) with timed pregnancies were allocated into four groups according to medication they received on day 17 to term. Rats were randomised into a sham-treated group (group I, n=10) and groups treated with L-NAME, 50 mg/day i.p., only (group II, n=10), L-NAME + quercetine, 10mg/kg i.p. (group III, n=10) and L-NAME + glutathione, 60 mg/kg i.p. (group IV, n=10). Blood levels of superoxide dismutase (SOD), catalase (CAT) and malonyldialdehyde (MDA) were assessed on day 22 of gestation. Intracardiac blood sampling and hysterotomy were performed on day 22 of gestation. Mean systolic BP (measured with a tail-cuff device), level of proteinuria, total urine output, pups birth weight and percentages of live and of dead pups were recorded. RESULTS: Mean systolic BP and SOD, CAT and MDA levels were higher in rats infused with L-NAME than in the sham-treated group. In group IV, SOD levels were lower than in group II (P <0.001). A linear positive correlation between BPs on day 20 and SOD levels (rp=0.39) was recorded, as were negative correlations between level of proteinuria and SOD levels (rp=-0.39) and between CAT and MDA levels (rp=-0.39). Birth weights were higher in the sham-treated group than in the other groups (P <0.001). Pups of hypertensive gravid rats treated with antioxidants had better survival rates than those of rats in group II and the sham-treated group (Chi-square=15.9, d.f.: 3, P <0.01).However, no correlation was detected between higher pup mortality rate and birth weight of pups. CONCLUSION: In this rat model of pre-eclampsia, adverse outcomes, such as proteinuria and high neonatal death rate, are reversed by exogenous antioxidant use, even though no significant improvement is detected in terms of BP and birth weight of pups.

Effect of leptin on healing of colonic anastomoses in rats.

BACKGROUND/AIMS: Anastomotic leaks are continuing to be the source of major morbidity in colorectal surgery. Previous studies have shown that leptin acts as a growth factor for several cell types. The aim of this study was to evaluate the effect of leptin on healing of colonic anastomoses in rats. METHODOLOGY: Forty-eight rats were divided into 5 groups. Group I (n=8) sham; group II (n=10) control; right colonic anastomosis, group III (n=10); following right colonic anastomosis, treated with leptin twice-daily 1 mg/kg intraperitoneally, group IV (n=10); before right colonic anastomosis, 45 min of colonic ischemia has been created, group V (n=10); following 45 min of colonic ischemia and right colonic anastomosis, leptin was given twice-daily 1 mg/kg intraperitoneally. On the 7th postoperative day relaparotomy was performed. Bursting pressure (BP), tissue hydroxyproline concentrations (THPC), and histopathologic properties of anastomoses; vascular tissue proliferation (VTP), collagen tissue proliferation (CTP), polymorphonuclear leukocyte infiltration (PMNLI), mononuclear leukocyte infiltration (MNLI) were analyzed and results were compared statistically. RESULTS: BP and THPC were found to be significantly higher in group III and group V in comparison with group II and group IV respectively (P<0.05). Histopathologically, leptin significantly increased VTP, CTP, MNLI (P<0.001), and significantly decreased PMNLI (p<0.05) on non-ischemic and ischemic colonic anastomoses. CONCLUSIONS: Leptin can be used safely in colorectal surgery since it accelerates the healing of colonic anastomoses.

The effects of isosorbide dinitrate on methemoglobin reductase enzyme activity and antioxidant states.

Isosorbide dinitrate (ISDN) has been used in the treatment of ischaemic cardiovascular diseases for many years. ISDN is the most popular nitric oxide donor and causes methemoglobinemia as an important side-effect. The purpose of this study was to examine antioxidant states and methemoglobin reductase activity after giving ISDN and ISDN plus vitamin E. Rats were divided into three groups according to the treatment: control group, ISDN group and ISDN plus vit. E group. We measured reduced glutathione in blood (GSH), plasma malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and NADH-dependent methemoglobin reductase activities. In the ISDN group, plasma MDA levels were significantly high compared to the control and ISDN + vit. E groups (p < 0.001). In the ISDN and ISDN + vit. E groups, blood GSH levels were higher than those of the control group (p < 0.05). Changes of SOD and GPx activities were not significant. In the ISDN and ISDN + vit. E groups the erythrocyte catalase and NADH-dependent methemoglobin reductase activities were significantly higher than that in the control group (p < 0.001). We conclude that oxidant drugs such as ISDN need to be carefully used because of lipid peroxidation and methemoglobinemia. These findings support the notion that vitamine E protects tissues against oxidative stress.

Lazaroid attenuates edema by stabilizing ATPase in the traumatized rat brain.

OBJECTIVE: The aim of the present study was to determine the potential therapeutic value of the lazaroid U-83836E on blood brain barrier (BBB) breakdown and edema with respect to the changes in the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-adenosinetriphosphatase (ATPase) activities, tissue malondialdehyde levels and the neuronal viability in the rat brain subjected to cerebral trauma. METHODS: Traumatic brain injury (TBI) was introduced by applying a 75 gm. cm force to the right parietal cortex using the weight-drop method. The first set of animals was used for determining time course changes of the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-ATPase and the malondialdehyde levels and were sacrificed 2, 6 and 24h after lesion production. A group of the animals was treated with U-83836E proir to TBI and sacrificed 24h after cerebral injury. A second set of animals was used for evaluating the alterations in BBB disruption and tissue water content and were sacrificed 2, 6 and 24h after lesion production. Two groups of animals were treated with U-83836E and sacrificed after 2 and 24h following TBI. U-83836E was given intraperitoneally thirty minutes before trauma at a dose of 10 mg/kg. Neuronal necrosis was also evaluated in the groups of U-83836E and physiological saline-treated animals. RESULTS: Extravasation of Evans blue into the traumatized hemisphere was maximum at 2h (p<0.001) and returned close to the control levels at 24h after TBI (p>0.05). Edema had developed progressively over time and reached the maximum degree of 2.1% (p<0.001) at 24h. U-83836E showed no effect on the BBB breakdown and the tissue water content at 2h and still had no effect on the BBB breakdown after 24h following the trauma (p>0.05), although it reduced edema after 24h (p<0.01). The losses of Na+/K+ and Mg(2+)/Ca(2+)-ATPase activities were found as 39.5% (p<0.001) and 29.4% (p<0.01) of the control value, respectively, and remained at the decreased levels throughout the experiment. Malondialdehyde level continued to increase over time reaching up to 209% (p<0.001) of the control value 24h after TBI. Both ATPase activities were improved to near control values (p>.05) by the effect of U-83836E. U-83836E inhibited the increase of lipid peroxidation (p<0.001) and also salvaged neuronal necrosis (p<0.05). CONCLUSION: U-83836E given prophylactically after cerebral trauma appears to reduce edema, possibly by inhibiting increases in lipid peroxidation and by stabilizing ATPase. Further studies are recommended to verify the similar effects of the brain penetrating lazaroids when they are given after trauma.

The effect of N-acetyl serotonin on ultraviolet-radiation-induced cataracts in rats.

AIMS: To investigate the effects of ultraviolet radiation (UVR) on cataract development in rat lenses and whether or not N-acetyl serotonin has an effect on changes in these lenses. MATERIAL AND METHODS: The study was performed using 5 groups of Sprague-Dawley albino rats, with each group consisting of 15 rats. The 5th group being the control group did not receive any applications, whilst the other 4 groups received a daily dose of 0.2 J/cm(2)/day UVR (305 nm wavelength) for 60 days. A dose of 4 mg/kg/0.1 ml N-acetyl serotonin was injected intraperitoneally to group 1 and group 2 every day and on alternate days, respectively. Group 3 received an intraperitoneal injection of 0.1 ml phosphate buffer solution every day, whilst group 4 received no injection. On the 60th day, an intracardiac withdrawal of blood was performed, after the rats had been anesthetized with ether. Following the withdrawal of blood, the rats were killed using a high dose of ether and their eyes were enucleated. The lens fresh weights, plasma malondialdehyde (P-MDA), erythrocyte glutathione peroxidase (E-GSHPx), erythrocyte glutathione reductase, blood reduced glutathione (B-RGSH), erythrocyte catalase (E-CAT), lenticular malondialdehyde, lenticular superoxide dismutase (L-SOD), lenticular glutathione peroxidase (L-GSHPx) and lenticular glutathione (L-GSH) levels were all assessed. RESULTS: The lens fresh weights were determined to be lower in group 1 and in the control group in comparison with the other groups (p < 0.01). Whilst the P-MDA level was found to be lower (p < 0.001), the E-GSHPx level was higher (p < 0.01) in the control group than in the other groups. The E-GSHPx level was higher in groups 1 and 2 than in groups 3 and 4 (p < 0.01). The B-RGSH level was higher in the control group than in the other groups (p < 0.001). The E-CAT level was higher in both the control group and group 1 than in groups 2, 3 and 4 (p < 0.01), whilst it was higher in group 2 when compared to groups 3 and 4 (p < 0.01). The L-SOD levels were found to be higher in the control group and group 1 than in groups 2, 3 and 4 (p < 0.001). Whilst the L-GSHPx levels were determined to be higher only in the control group (p < 0.001), the L-GSH levels were higher in the control group and group 1 than in the other groups (p < 0.001). CONCLUSIONS: In recent years, the depletion of the atmospheric ozone layer has resulted in the penetration of more UVR to the earth, which causes various effects on different tissues of organisms. N-acetyl serotonin, a melatonin precursor, may well be effective in the prevention of the negative effects induced by the UVR upon the lens tissue, in which case the capability of melatonin to capture free radicals as well as its antioxidative properties should be taken into consideration.

Effects of intrarectal and intraperitoneal N(G)-nitro-L-arginine methyl ester treatment in 2,4,6-trinitrobenzenesulfonic acid induced colitis in rats.

Inflammatory bowel disease (IBD) has been associated with an increased generation of nitric oxide (NO). Different authors have shown that NO in IBD can be either harmful or protective. The aim of this study was to investigate the efficiency of intrarectal (i.r.) and intraperitoneal (i.p.) application of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor, in experimental acute colitis in the rats. Acute colitis was induced in rats by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. Twenty-eight rats were divided into four groups. L-NAME (50 mg/kg/day) was administered i.p. (Group 1) and i.r. (Group 2) for 7 days following the day when colitis was induced. Group 3 rats were not given any treatment after induction of colitis. Control group rats were given saline solution i.r. instead of TNBS. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic damage. The severity of colitis was assessed by microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, inflammatory cell infiltration, and vascular dilatation. Rectal tissue myeloperoxidase (MPO) activity and serum-rectal tissue nitrite levels were measured. Serum and rectal tissue nitrite levels increased in Group 3 rats. Both i.p. and i.r. L-NAME treatment significantly reduced serum and rectal tissue nitrite levels, but no effect on MPO activity and histologic damage score was observed. Under the present conditions we concluded i.r. and i.p. L-NAME treatment, applied at the dosage of 50 mg/kg/day, does not have any protective effect on the colonic injury.

The effects of exogenous glutathione on reduced glutathione level, glutathione peroxidase and glutathione reductase activities of rats with different ages and gender after whole-body Γ-irradiation.

Age-and gender-related changes on reduced glutathione (GSH) level, glutathione peroxidase (GPx) and glutathione reductase (GR) activities in the liver of rat exposed to different dose of whole-body g-ray irradiation were determined. In addition, the effect of administration of exogenous GSH on endogenous GSH levels, GPx and GR activities was investigated. For this aim, male and female rats aged 1 and 5 moths were divided into two groups as g-ray and g-ray+GSH. Both groups were again divided into four groups as irradiated with 2, 4, 6 and 8 Gy doses. GSH level and GPx activity did not change with age while GR activity was decreased with age. Gender-dependent changes in GPx and GR activities were observed, but GSH values were not affect by sex. GSH levels, GPx and GR activities were not observed dose-associated changes of g-irradiation. GSH level and GPx activity in the 8Gy group were increased by GSH. GR activities of old male rats were found to be increased by glutathione in the 6 and 8Gy groups. These results indicate that radiation and administration of exogenous GSH affect gender-and age-dependent GSH level, GPx and GR activities in the rats.

The effect of quercetin on renal ischemia and reperfusion injury in the rat.

Renal ischemia-reperfusion injury occurs in many clinical conditions such as hypovolemic shock, thromboembolism, injury and after renal transplantation. Under these conditions, ROS are considered to be the reason for cellular damage. Bioflavonoids have antioxidant and renoprotective properties. We studied the effect of quercetin, a bioflavonoid, on ischemia and reperfusion in rats. The rats (n = 28) were separated into three groups. Group I was the control group. Animals in groups II (IR) and III (IR + Q) underwent 30 min ischemia and 45 min reperfusion, respectively. Rats, in group III, also received 50 mg kg(-1) quercetin before 45 min of reperfusion. The activities of SOD, CAT, GPx, and concentrations of GSH and GSSGR were determined in renal cortex and erythrocytes. Also, the levels of MDA in renal cortex and plasma, and XO in renal cortex were measured in these groups. The renal cortex XO levels in the IR group were higher than that of the control and IR+Q groups (p<0.001). The renal cortex and plasma MDA levels in the IR group were also found to be higher than the control and IR+Q groups (p<0.01, and p<0.001, respectively). However, a decrease in MAD level of the IR+Q group was found in renal cortex and erythrocytes. In addition, SOD, CAT, and GPx activities in renal cortex and erythrocytes of quercetin-treated animals were enhanced compared to animals of the IR group. Furthermore, there were no significant differences in the SOD, CAT, and GPx activities of the control and IR+Q group. A reduction of GSH and GSSGR levels in IR and IR+Q groups was detected but no significant differences were found between these groups. This study stresses that high concentration of ROS leads to renal ischemia and reperfusion, and quercetin reduces the renal injury by preventing the oxidative stress dependent on ischemia and reperfusion. Quercetin may be used in renal transplantation as an antioxidant drug.

Protective effects of quercetin on ultraviolet A light-induced oxidative stress in the blood of rat.

The oxidative effects of ultraviolet A (UVA) light (320-400 nm) and the antioxidant effects of quercetin were examined in rat blood. For this purpose, rats were divided into three groups: control, ultraviolet (UV) and ultraviolet + quercetin (UV + Q). The UV and UV + Q groups were irradiated for 4 h a day with UVA light (1.25 mW cm(2)) during periods of 3, 6 and 9 days. Quercetin (50 mg kg(-1) body wt.) was administered intraperitoneally in the UV + Q group rats before irradiation periods. Blood was taken 3, 6 and 9 days post-treatment. Plasma malondialdehyde (MDA) levels significantly increased after 9 days of daily exposure to UVA. Whole blood glutathione (GSH) levels significantly declined after 3-9 days of irradiation. Glutathione peroxidase activity on days 6 and 9 and glutathione reductase activities on days 3, 6 and 9 post-irradiation were diminished significantly. Superoxide dismutase and catalase activities decreased significantly 3-9 days post-irradiation. The administration of quercetin before the 9-day period of irradiation significantly reduced the increase in plasma MDA value. Whole blood GSH levels significantly decreased with the administration of quercetin on all days. Quercetin significantly increased antioxidant enzymes diminished by UVA irradiation. Exposure of rats to UVA light leads to oxidative stress, reflected by increased MDA and reduced antioxidant enzyme levels. The administration of quercetin appears to be a useful approach to reduce the damage produced by UVA radiation.

Age-related changes in the glutathione redox system.

The effect of aging on the glutathione redox system was evaluated in this study. For this purpose, we determined reduced glutathione (GSH) and oxidized glutathione (GSSG) in whole blood, glutathione peroxidase (GPx) and glutathione reductase (GSSGR) in erythrocytes and selenium (Se) in plasma in 176 healthy individuals. We also calculated GSH/GSSG molar ratios. These subjects were divided into five groups: group 1 (n=25; 0.2-1 years old); group 2 (n=28; 2-11 years old); group 3 (n=23; 12-24 years old); group 4 (n=40; 25-40 years old); group 5 (n=60; 41-69 years old). GSH levels in groups 1 and 5 were significantly lower than the other groups (p<0.001). Conversely, GSSG levels were significantly high in these periods (p<0.001). The GSH/GSSG molar ratio was found to be low both in the first year of life and in the oldest group (p<0.001, respectively). GPx activity in group 5 was increased as compared to the other groups (p<0.001). GSSGR activity was significantly lower in the oldest groups than in the other groups (p<0.001). Se levels were found to be low in the oldest group (p<0.001). Selenium levels of women in group 5 were significantly high as compared to the men (p<0.01). We found negative correlations between age and GSH levels (r=0.402; p<0.001), selenium levels (r=0.454; p<0.001), GSH/GSSG molar ratio (r=0.557; p<0.001) and GSSGR activity (r=0.556; p<0.001). There were positive correlations between age and GPx (r=0.538; p<0.001) and GSSG level (r=0.551; p<0.001). In conclusion, our findings show that the glutathione redox system is affected by age. Oxidative stress increases during the aging process. There is no effect of aging on the glutathione redox system according to sex except for the Se level.