Stereological examination of curcumin's effects on hippocampal damage caused by the anti-epileptic drugs phenobarbital and valproic acid in the developing rat brain.

The anti-epileptic drugs phenobarbital and valproic acid have an extremely strong negative effect on cognitive processes such as learning and memory in the developing brain. We examined whether or not curcumin has protective effects on neuronal injury caused by these drugs in the developing rat brain. Young male Wistar rats were studied in two groups, a 7 days old and a 14 days old group (35 rats in each). Both groups were then divided into 7 sub-groups as the control, curcumin, dimethylsulfoxide, phenobarbital, valproic acid, phenobarbital + curcumin, and valproic acid + curcumin groups (n = 5 in each group). At 24 h after the intraperitoneal injection of the compounds, the rats were sacrificed, and the hippocampal tissue was subjected to stereological analysis with the optical fractionation method. Total numbers of neurons in the hippocampus of the 7 days old and 14 days old rats were calculated. It was found that treatment with phenobarbital resulted in a loss of 43% of the neurons, and valproic acid induced a loss of 57% of the neurons in the 7 days old rats. Curcumin prevented this loss significantly with only 19% in the phenobarbital group and 41% in the valproic acid group. In the 14 days old rat groups, phenobarbital was found to reduce the number of neurons by 30%, and valproic acid reduced it by 38%. Curcumin treatment limited neuronal loss to 3% in the phenobarbital + curcumin group and 10% in the valproic acid + curcumin group. These data strongly indicate that curcumin is a protective agent and prevents hippocampal neuronal damage induced by phenobarbital and valproic acid treatment.

Effects of preoperative conventional and hyperfractionated radiotherapy on the healing of rat colonic anastomoses.

BACKGROUND: One problem associated with end to end anastomoses after preoperative radiotherapy is leakage. The strength of the anastomoses is very important. Fractionation schedules are widely under investigation to achieve higher doses with less toxicity and high curative potential. The aim of this study was to compare preoperative conventional and hyperfractionated radiotherapy effects on anastomoses. MATERIALS AND METHODS: Sixty Wistar albino rats were divided into 3 groups: control, conventional radiotherapy (2 Gy/fraction, total 44 Gy), and hyperfractionated radiotherapy (1.2 Gy/fraction, total 52.8 Gy). 5 weeks after completion of the treatment, the rats underwent end to end anastomoses to the rectum. Following the surgery, the bursting pressure of the anastomoses and the hydroxyproline levels were measured on days 3 and 7. RESULTS: The bursting pressure was lower in both radiotherapy groups on the 3rd day. On day 7, the results of the conventional radiotherapy arm matched those of the control group, but the results of the hyperfractionated group did not (p = 0.001). On day 3, hydroxyproline levels were significantly lower in both radiotherapy groups than in the control group (p = 0.001). On the 7th day, the statistical difference disappeared within the radiotherapy groups. However, the hydroxyproline levels of the 2 radiotherapy arms were still lower than those of the control group (p = 0.001). CONCLUSION: Hyperfractionation strongly inhibits collagen synthesis and is associated with protracted healing.

The effect of glucose-insulin-potassium treatment on myocardial oxidative stress in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

OBJECTIVES: In this study, we sought to examine the effect of glucose-insulin-potassium (GIK) treatment on oxidative stress in patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary interventions (PCIs). METHODS: Patients with ACSs who had been electively treated with a stent implantation into the culprit vessel were included in this study. Patients were divided into two groups and were randomly administered either the GIK treatment (GIK group; n=28) or isotonic NaCl (control group; n=19) infusion during PCI. Blood samples from the coronary artery ostium (CO) were collected through the femoral artery and from the coronary sinus (CS) through the femoral vein, before and immediately after PCI. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were measured. RESULTS: A total of 47 patients were included in the study. SOD, CAT, and GSH-Px activities, whether in the CO or the CS, were similar in both the GIK and control groups before the intervention (P>0.05). In the control group, SOD (in both the CO and the CS), CAT (in the CS), and GSH-Px (in the CS) activities were higher compared with baseline values (P<0.05). Such increases were, however, not seen in the GIK group (P>0.05). Although the CS-CO activity differences (venous-arterial) of SOD, CAT, and GSH-Px, which are parameters of myocardial reactive antioxidant enzyme production, were increased in the control group, there was no increase in the GIK group. CONCLUSIONS: In patients with ACSs, reactive local enzyme activity increases for the scavenging to myocardial-free radicals during PCI. Administration of a solution of GIK as a metabolic support agent might prevent oxidative stress in the myocardial level, in these patients.

Effect of glucose-insulin-potassium infusion on oxidative stress in patients with dilated cardiomyopathy.

OBJECTIVE: To investigate the effect of glucose-insulin-potassium (GIK) infusion on erythrocyte antioxidant enzyme activity levels during therapy and post-therapy in patients with dilated cardiomyopathy (DCM). METHODS: Forty-one patients with DCM were enrolled in the present study. GIK solution (50 U of insulin in 500 mL of 30% glucose, plus 60 mmol/L KCl), in addition to the standard treatment, was administered by 24 h infusion in 28 patients (GIK group). In the remaining 13 patients (control group), 0.9% NaCl solution was administered. Venous blood samples from all patients were collected at baseline, during therapy (2 h, 8 h, 12 h and 24 h after baseline) and after therapy (48 h after baseline). The activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHP) were measured. RESULTS: In the GIK group, SOD values showed a significant increase at 24 h and 48 h compared with baseline and 2 h values (P<0.05). An increasing trend in CAT activity was observed during and after GIK infusion compared with baseline (0 h) values. However, these differences were not statistically significant (P>0.05). With regard to GSHP activity, no significant change was found in the GIK group during follow-up (P>0.05). In the control group, SOD, CAT and GSHP activity levels measured during and after therapy were found to be similar to those measured at baseline (P>0.05). CONCLUSION: Administration of GIK solution, in addition to standard therapy, in patients with DCM may improve the metabolic scope of the disease by reducing myocardial oxidative stress.

Effects of omeprazole and gentamicin on the biochemical and histopathological alterations of the hypoxia/ reoxygenation induced intestinal injury in newborn rats.

We utilized a newborn rat model of hypoxia/reoxygenation (H/R) that resembles human necrotizing enterocolitis (NEC) to investigate the effects of omeprazole and/or gentamicin on the formation of free oxygen radicals (FOR) and bowel histopathology. For H/R, 1-day-old rats were placed into a chamber of 100% CO2 for 5 min, then they were reoxygenized for the next 5 min. The rats (n = 70) were divided into seven groups: group 1 (control), group 2 (H/R), group 3 (omeprazole), group 4 (H/R + omeprazole), group 5 (gentamicin), group 6 (H/R + gentamicin), group 7 (H/R + omeprazole + gentamicin). Gentamicin and/or omeprazole were given orally for 3 days, then all animals were killed; bowel specimens were harvested. Histopathologic injury scores (HIS) and malonyldialdehyde (MDA) and XO/(XO+XDH) rates (XO; xanthine oxidase, XDH; xanthine dehydrogenase) were measured, which reflect the FOR levels. In group 2, the HIS was significantly higher than groups 4 and 6. The mean MDA values in groups 1-7 were as follows: 54.16, 104.2, 56.85, 63.43, 62.31, 76.85, 79.13, respectively. The mean XO/(XO + XDH) levels were 0.306, 0.461, 0.286, 0.335, 0.323, 0.410, 0.375 from groups 1 -7, respectively. Group 2 rats had significantly more MDA and XO/(XO + XDH) rates versus other groups (P < 001). Histopathologic injury and biochemical results were significantly more severe in group 2 than in groups 4 and 6 (P < 001). There was no difference between groups 1 and 4 according to XO/(XO + XDH) rates. In newborn rats, H/R produces FOR, which cause serious intestinal damage. Omeprazole and/or gentamicin reduce biochemical and histopathologic bowel damage. This effect was more obvious in omeprazole treated rats. We think omeprazole may open new insights into the treatment of H/R related bowel injuries like NEC.

Reactive oxygen species scavenging activity during periodontal mucoperiosteal healing: an experimental study in dogs.

Excessive release of reactive oxygen species (ROS) in wounded tissue due to inflammation and ischaemia is a deleterious and destructive phenomenon for the healing process. Hence, scavenging of ROS is one of the essential steps in normal wound repair. In this study, we presented a profile of free radical scavenging enzyme (FRSE) activity of periodontal mucoperiosteal wounds in order to investigate ROS activity during periodontal wound healing. Mucoperiosteal periodontal flaps were elevated in the mandibular buccal region of seven dogs between the first premolar and first molar teeth, creating acute incisional wounds in the inner side of the flaps and they were replaced 30 min after elevation. Gingival samples taken from certain biopsy regions at baseline (before flap elevation), day 3, 12, 21 and 30 were processed for detection of active amounts of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). All enzyme activities had increased by more than 100% of their baseline levels by day 3. SOD activity decreased gradually from days 3 to 30 and reached a level lower than the baseline value. The increase in CAT activity continued until day 21, and decreased to a level higher than the baseline value by day 30. GPX also decreased from day 3, and reached a level less than its baseline value by day 30. Our results suggest that FRSEs may contribute to the detoxification of ROS during periodontal mucoperiosteal healing. This relationship may be utilized to facilitate soft tissue and/or flap management in periodontal or intra-oral treatments.

The effect of polylactide membranes on the levels of reactive oxygen species in periodontal flaps during wound healing.

It is consented that reactive oxygen species (ROS) are deleterious to wound healing process due to the harmful effects on cells and tissues. Absorbable synthetic biomaterials are considered to be degraded via ROS. Free-radical-scavenging enzymes (FRSE) are a cytoprotective enzymal group that has an essential role in the reduction, de-activation and removal of ROS as well as regulating wound healing process. In the present study, synthetic and absorbable polylactide (PLA) barrier membranes were evaluated by means of ROS activity levels during degradation in the healing periodontal flaps measuring the activity of FRSE superoxide dismutase (SOD) and catalase (CAT). Gingival biopsies taken from 10 patients allowing both guided tissue regeneration (test) and conventional flap surgery (control) before and 1 month after the operations were processed and the supernatants were studied by Mc Cord and Fridovich, Flohe and Otting, and Luck methods to measure total SOD and CAT levels respectively. A significantly increased enzyme activity of SOD and CAT was observed in both groups (p<0.05). SOD activity change was 62.92% in the test and 3.97% in the control group, and, CAT activity change was 48.04% in the test and 11.58% in the control group. Our results suggest that ROS, particularly superoxide anions, may contribute to the degradation phase of PLA membranes and this may affect the wound healing of periodontium at least for one-month period.