The effects of steroidal and non-steroidal anti-inflammatory drugs on tracheal wound healing in an experimental rat model.

OBJECTIVES: The effect of non-steroidal anti-inflammatory drugs (NSAID), mostly used for postoperative analgesic purposes for wound healing, is still a matter of debate. Our goal was to evaluate the effects of the most widely used NSAID and corticosteroids after surgical operations on tracheal wound healing in an experimental rat model. METHODS: Thirty-nine male Wistar albino rats were included in this study. Tracheotomy was performed in 32 rats; then they were divided into 3 groups. After the first day, the animals in group 1 were treated with an NSAID (diclofenac 10 mg/kg/day) (NSAID, n = 12) for 7 days; the animals in group 2 were treated with a corticosteroid (dexamethasone, 2 × 0.1 mg/kg/day) (steroid, n = 10) for 7 days; the animals in group 3 (control, n = 10) were not given any medications. For a fourth group (histological control, n = 7), in order to evaluate normal morphological and histological characteristics, neither surgery nor medication was used. Five rats were eliminated from the study (2 rats in the NSAID group died and 3 rats in the steroid group developed local wound infections). The drop-out rate was 12.8%. Histological characteristics, inflammation, fibrosis, necrosis, neochondrogenesis, neovascularization and epithelization were evaluated in 34 rats. Non-parametric tests were used for statistical analysis. RESULTS: Inflammation, vascularization and number of fibroblasts and chondrocytes were significantly higher in the control group than in the histological control group. There was some reduction in all parameters except vascularization in the NSAID group (P > 0.05). When the steroid group was compared to the NSAID group, inflammation (P < 0.05), vascularization and number of chondrocytes (P > 0.05) were more suppressed in the steroid group. The number of fibroblasts increased in the steroid group (P > 0.05). CONCLUSIONS: Steroids and NSAID may have negative effects on tracheal wound healing, probably by suppressing inflammation and fibroblast proliferation. NSAID was mostly used postoperatively for analgesic purposes and should be avoided.

Effects of pre- and postnatal exposure to extremely low-frequency electric fields on mismatch negativity component of the auditory event-related potentials: Relation to oxidative stress.

In our previous study, the developmental effects of extremely low-frequency electric fields (ELF-EF) on visual and somatosensory evoked potentials in adult rats were studied. There is no study so far examining the effects of 50 Hz electric field (EF) on mismatch negativity (MMN) recordings after exposure of rats during development. Therefore, our present study aimed to investigate MMN and oxidative brain damage in rats exposed to EF (12 kV/m, 1 h/day). Rats were divided into four groups, namely control (C), prenatal (Pr), postnatal (Po), and prenatal+postnatal (PP). Pregnant rats of Pr and PP groups were exposed to EF during pregnancy. Following birth, rats of PP and Po groups were exposed to EF for three months. After exposure to EF, MMN was recorded by electrodes positioned stereotaxically to the surface of the dura, and then brain tissues were removed for histological and biochemical analyses. The MMN amplitude was higher to deviant tones than to standard tones. It was decreased in all experimental groups compared with the C group. 4-Hydroxy-2-nonenal (4-HNE) levels were significantly increased in the Po group with respect to the C group, whereas they were significantly decreased in the PP group compared with Pr and Po groups. Protein carbonyl levels were significantly decreased in the PP group compared with C, Pr, and Po groups. EF decreased MMN amplitudes were possibly induced by lipid peroxidation.

2100-MHz electromagnetic fields have different effects on visual evoked potentials and oxidant/antioxidant status depending on exposure duration.

The purpose of the present study was to investigate the duration effects of 2100-MHz electromagnetic field (EMF) on visual evoked potentials (VEPs) and to assess lipid peroxidation (LPO), nitric oxide (NO) production and antioxidant status of EMF exposed rats. Rats were randomized to following groups: Sham rats (S1 and S10) and rats exposed to 2100-MHz EMF (E1 and E10) for 2h/day for 1 or 10 weeks, respectively. At the end of experimental periods, VEPs were recorded under anesthesia. Brain thiobarbituric acid reactive substances (TBARS) and 4-hydroxy-2-nonenal (4-HNE) levels were significantly decreased in the E1 whereas increased in the E10 compared with their control groups. While brain catalase (CAT), glutathione peroxidase (GSH-Px) activities and NO and glutathione (GSH) levels were significantly increased in the E1, reduction of superoxide dismutase (SOD) activity was detected in the same group compared with the S1. Conversely, decreased CAT, GSH-Px activities and NO levels were observed in the E10 compared with the S10. Latencies of all VEP components were shortened in the E1 compared with the S1, whereas latencies of all VEP components, except P1, were prolonged in the E10 compared with the S10. There was a positive correlation between all VEP latencies and brain TBARS and 4-HNE values. Consequently, it could be concluded that different effects of EMFs on VEPs depend on exposure duration. In addition, our results indicated that short-term EMF could provide protective effects, while long-term EMF could have an adverse effect on VEPs and oxidant/antioxidant status.

The developmental effects of extremely low frequency electric fields on visual and somatosensory evoked potentials in adult rats.

The purpose of our study was to investigate the developmental effects of extremely low frequency electric fields (ELF-EFs) on visual evoked potentials (VEPs) and somatosensory-evoked potentials (SEPs) and to examine the relationship between lipid peroxidation and changes of these potentials. In this context, thiobarbituric acid reactive substances (TBARS) levels were determined as an indicator of lipid peroxidation. Wistar albino female rats were divided into four groups; Control (C), gestational (prenatal) exposure (Pr), gestational+ postnatal exposure (PP) and postnatal exposure (Po) groups. Pregnant rats of Pr and PP groups were exposed to 50 Hz electric field (EF) (12 kV/m; 1 h/day), while those of C and Po groups were placed in an inactive system during pregnancy. Following parturition, rats of PP and Po groups were exposed to ELF-EFs whereas rats of C and Pr groups were kept under the same experimental conditions without being exposed to any EF during 68 days. On postnatal day 90, rats were prepared for VEP and SEP recordings. The latencies of VEP components in all experimental groups were significantly prolonged versus C group. For SEPs, all components of PP group, P2, N2 components of Pr group and P1, P2, N2 components of Po group were delayed versus C group. As brain TBARS levels were significantly increased in Pr and Po groups, retina TBARS levels were significantly elevated in all experimental groups versus C group. In conclusion, alterations seen in evoked potentials, at least partly, could be explained by lipid peroxidation in the retina and brain.

The effect of different strengths of extremely low-frequency electric fields on antioxidant status, lipid peroxidation, and visual evoked potentials.

The aim of the study was to investigate the effects of extremely low-frequency electric field (ELF EF) on visual evoked potential (VEP), thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), total oxidant status (TOS), and oxidant stress index (OSI). Thirty female Wistar rats, aged 3 months, were divided into three equal groups: Control (C), the group exposed to EF at 12 kV/m strength (E12), and the group exposed to EF at 18 kV/m strength (E18). Electric field was applied to the E12 and E18 groups for 14 days (1 h/day). Brain and retina TBARS, TOS, and OSI were significantly increased in the E12 and E18 groups with respect to the control group. Also, TBARS levels were significantly increased in the E18 group compared with the E12 group. Electric fields significantly decreased TAS levels in both brain and retina in E12 and E18 groups with respect to the control group. All VEP components were significantly prolonged in rats exposed to electric fields compared to control group. In addition, all latencies of VEP components were increased in the E18 group with respect to the E12 group. It is conceivable to suggest that EF-induced lipid peroxidation may play an important role in changes of VEP parameters.

Protective effects of erdosteine on amikacin induced visual evoked potentials and lipid peroxidation alterations.

PURPOSE: We aimed at investigating the effect of erdosteine administration on amikacin induced visual evoked potentials (VEPs) alterations in rats. METHODS: For this purpose, forty male Wistar rats were divided into 4 groups: control, amikacin treated, erdosteine treated, and amikacin + erdosteine treated. Amikacin (600 mg/kg/day) was applied as a single dose of intramuscular injection for 14 days, and 10 mg/kg/day erdosteine was given by gastric gavage for the same period. We recorded all VEP components and measured plasma thiobarbituric acid reactive substance (TBARS) levels in all groups. RESULTS: Amikacin increased the latencies of all VEP components (P1, N1, P2, N2, and P3) and elevated plasma TBARS levels compared with control and erdosteine treated rats (p < 0,01). However, prolonged latencies of VEP components in amikacin treated rats returned to control levels after erdostein administration. Treatment of amikacin and erdosteine together significantly decreased plasma TBARS levels (0.05 ± 0.018 nmol/g protein) compared with amikacin group (0.12 ± 0.038 nmol/g protein). CONCLUSIONS: These results show that erdosteine has a protective effect on amikacin induced changes in the visual system.

Dose-dependent effect of nutritional sulfite intake on visual evoked potentials and lipid peroxidation.

The aim of this study was to clarify the dose-dependent effect of sulfite (SO3²â») ingestion on brain and retina by means of electrophysiological and biochemical parameters. Fifty two male Wistar rats, aged 3 months, were randomized into four experimental groups of 13 rats as follows; control (C), sulfite treated groups (S(1); 10 mg/kg/day, S2; 100mg/kg/day, S3; 260 mg/kg/day). Control rats were administered distilled water, while the other three groups were given sodium metabisulfite (Na2S2O5) of amounts mentioned above, via gavage for a period of 35 days. All components of visual evoked potential (VEP) were prolonged in S2 and S3 groups compared with S1 and C groups. Plasma-S-sulfonate levels, which are an indicator of sulfur dioxide (SO2) exposure, were increased in Na2S2O5 treated groups in a dose-dependent manner. Furthermore, the significant increments in thiobarbituric acid reactive substances (TBARS) and 4-hydroxy-2-nonenal (4-HNE) levels occurred with increasing intake of Na2S2O5. Though not significant, glutathione (GSH) and oxidized glutathione (GSSG) levels were observed to decrease with increasing doses of Na2S2O5. In conclusion, Na2S2O5 treatment in rats caused a dose-dependent increase in lipid peroxidation and all VEP latencies. The data indicate that lipid peroxidation could play an important role in sulfite toxicity.

Suppressive effect of astaxanthin on retinal injury induced by elevated intraocular pressure.

The aim of this study was to clarify the possible protective effect of astaxanthin (ASX) on the retina in rats with elevated intraocular pressure (EIOP). Rats were randomly divided into two groups which received olive oil or 5mg/kg/day ASX for a period of 8 weeks. Elevated intraocular pressure was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. At the end of the experimental period, neuroprotective effect of ASX was determined via electrophysiological measurements of visual evoked potentials (VEP) and rats were subsequently sacrificed to obtain enucleated globes which were divided into four groups including control, ASX treated, EIOP, EIOP+ASX treated. Retinoprotective properties of ASX were determined by evaluating retinal apoptosis, protein carbonyl levels and nitric oxide synthase-2 (NOS-2) expression. Latencies of all VEP components were significantly prolonged in EIOP and returned to control levels following ASX administration. When compared to controls, EIOP significantly increased retinal protein oxidation which returned to baseline levels in ASX treated EIOP group. NOS-2 expression determined by Western blot analysis and immunohistochemical staining was significantly greater in rats with EIOP compared to ASX and control groups. Retinal TUNEL staining showed apoptosis in all EIOP groups; however ASX treatment significantly decreased the percent of apoptotic cells when compared to non treated ocular hypertensive controls. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of ASX in ocular hypertension.

The effect of heme oxygenase inhibition on visual evoked potentials.

This study investigated the effect of heme oxygenase (HO) inhibition on visual evoked potentials (VEPs). HO catalyzes the oxidative degradation of heme. Products of HO reaction are biliverdin, ferrous iron, and carbon monoxide (CO). CO is a signal molecule and is an endogenous modulator in the soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway. Rats were treated with HO inhibitors tin protoporphyrin IX (SnPP IX) or zinc protoporphyrin IX (ZnPP IX) or HO inducer sodium arsenite (Na-arsenite). Soluble guanylate cyclase is inhibited by 1H-[1,2,3]oxydiazolo[4,3-a]quinoxalin-1-one (ODQ) and induced by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1). VEPs were recorded under mild ether anesthesia with the help of stainless steel subdermal electrodes and a photic stimulator. SnPP IX, ODQ or SnPP IX + YC-1 injections significantly prolonged latencies of P3; however, Na-arsenite shortened latency of P3. It has been shown that HO affects VEPs.

Effect of alpha-lipoic acid on visual evoked potentials in rats exposed to sulfite.

This study aimed to investigate the effect of alpha-lipoic acid (LA) administration on sulfite-induced alterations in visual evoked potentials (VEPs). Fifty two male albino Wistar rats were randomized into four experimental groups as follows; control (C), LA treated (L), sodium metabisulfite (Na(2)S(2)O(5)) treated (S), Na(2)S(2)O(5)+LA treated (SL). Na(2)S(2)O(5) (260 mg/kg/day) and LA (100 mg/kg/day) were given by intragastric intubation for 5 weeks. The latencies of VEP components were significantly prolonged in the S group and returned to control levels following LA administration. Thiobarbituric acid reactive substances (TBARS) levels in the S group were significantly higher than those detected in controls. LA significantly decreased brain and retina TBARS levels in the SL group compared with the S group. Sulfite caused a significant decrease in retina and brain glutathione peroxidase (GPx) activities which was restored to control levels via LA administration. Brain glutathione (GSH):glutathione disulfide (GSSG) ratio was significantly increased in rats jointly treated with sulfite and LA compared to rats treated with sulfite alone. Though not significant, a similar increase in GSH:GSSG ratio was also observed in the retina of SL group. This study showed that LA is protective against sulfite-induced VEP alterations and oxidative stress in the brain and retina.

Effect of aminoguanidine on visual evoked potentials (VEPs), antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress.

The purpose of the study was to investigate the effect of aminoguanidine (AG) on visual evoked potentials (VEPs), thiobarbituric acid reactive substances (TBARS), the activities of Cu, Zn superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and nitrite/nitrate levels. Forty healthy male Wistar rats, aged 3 months, were divided into four equal groups: Control (C), the group treated with aminoguanidine (A), the group exposed to restraint stress (S), the group exposed to restraint stress and treated with aminoguanidine (AS). Chronic restraint stress was applied for 21 days (1 h/day) and aminoguanidine (50 mg/kg/day) was injected intraperitoneally to the A and AS groups for the same period. Aminoguanidine treatment significantly decreased retina and brain TBARS levels in rats exposed to restraint stress compared to rats exposed to restraint stress alone. Aminoguanidine treatment produced a significant decrease in brain and retina nitrite and nitrate levels with respect to the control groups. Aminoguanidine increased all antioxidant enzyme activities in both brain and retina in rats exposed to restraint stress compared to rats exposed to restraint stress alone. All VEP components were significantly decreased in AG treated rats exposed to restraint stress compared to rats exposed to restraint stress alone. Our study clearly showed that AG has the potential to prevent changes caused by stress.

The effect of lipoic acid on lipid peroxidation and visual evoked potentials (VEPs) in rats exposed to chronic restraint stress.

The purpose of the present study was to investigate the effect of lipoic acid on lipid peroxidation, nitric oxide production, and visual evoked potentials (VEPs) in rats exposed to chronic restraint stress and to examine whether lipoic acid could prevent VEP alterations that occurred in stress together with lipid peroxidation. Forty male wistar rats, aged three months, were used in the present study. They were equally divided into four groups: control (C), the group treated with lipoic acid (L), the group exposed to restraint stress (S), and the group exposed to stress and treated with lipoic acid (LS). Chronic restraint stress was applied for 21 days (1 h/day) and lipoic acid (100 mg/kg/day) was injected intraperitonally to the L and LS groups for the same period. Brain and retina TBARS levels were significantly increased in the S group compared with the C group. Lipoic acid reduced retina and brain TBARS levels in the L and LS groups compared with their corresponding control groups. Restraint stress significantly increased nitrite and nitrate levels in both brain and retina in the stress group with respect to the control group. Lipoic acid produced a significant decrease in brain and retina nitrite and nitrate levels of the L and LS groups comparing with their corresponding control groups. All latencies of VEP components were prolonged in the S group with respect to the C group. The study found significant correlations between VEPs latencies and TBARS and nitrite and nitrate levels of retina and brain. Lipoic acid decreased the latencies of all VEP components in the LS group whereas it did not affect them in the L group with respect to their control groups. In summary, lipoic acid treatment was found effective in preventing VEP and TBARS alterations caused by stress.

Effect of chronic restraint stress and alpha-lipoic acid on lipid peroxidation and antioxidant enzyme activities in rat peripheral organs.

OBJECTIVES: The aim of this study was to evaluate the effect of chronic restraint stress and alpha-lipoic acid (LA) administration on lipid peroxidation and antioxidant enzyme activities in rat peripheral organs. METHODS: Forty male wistar rats, aged 3 months were randomized to one of the following groups: control, restraint stress, LA treated and restraint stress+LA treated. Chronic restraint stress was applied for 21 days (1h/day) and LA (100 mg/kg/day) was administered intraperitoneally for the same period. RESULTS: Restraint stress had no statistically significant effect on lipid peroxidation, copper/zinc superoxide dismutase (Cu/Zn SOD), catalase (CAT) and glutathione peroxidase (GPx) activity in rat liver and heart, when compared to the control group. Lipid peroxidation, determined by measuring malondialdehyde (MDA) levels, was found to be increased in the kidney of restraint stress treated rats, compared to controls. Restraint stress-induced lipid peroxidation in the kidney was significantly decreased via LA treatment. Administration of LA also enhanced GPx and decreased Cu/Zn SOD activity in rat kidney, liver and heart, compared to the control group. CONCLUSIONS: The presented data shows that LA is a protective agent against restraint stress--the inducer of lipid peroxidation in the kidney. These findings also suggest that LA-induced changes in antioxidant enzyme activities in rat peripheral organs may contribute to their versatile effects observed in vivo.