Evaluation of babies with retinopathy of prematurity following intravitreal bevacizumab administration.

OBJECTIVE: In Turkiye, the increased likelihood of survival of small premature babies has resulted in a higher incidence of retinopathy of prematurity (ROP), which causes severe visual impairment in childhood. Early diagnosis and timely and proper treatment of ROP can prevent vision loss. This paper discusses cases of ROP treated with bevacizumab. METHODS: Patients treated with bevacizumab for ROP were evaluated retrospectively. Systolic and diastolic blood pressure values were recorded 1 day before and 2 weeks after bevacizumab administration. The Bayley III test, hearing test, eye examination, and neurological evaluation were performed. RESULTS: The mean composite Bayley III test scores for cognition, language, motor, social-emotional, and adaptive domains in 10 patients who received bevacizumab for ROP were 75±10.8, 73.4±15.4, 71.2±10.2, 88±23.7, and 65.4±13.8, respectively. The mean values of the day before the injection and the values of the 14 days after the injection were compared, it was seen that there was a significant increase in systolic blood pressure values, especially at the end of 1st day and 1st week after the surgery. Neurological examination results were abnormal in 50% of the cases. Vision problems were detected in 40% of the cases. About 30% of the babies failed the hearing test. CONCLUSION: Caution needs attention in the care of neonates until further studies of the long-term benefits and effects of bevacizumab therapy are completed.

Evaluation of dry eye and meibomian gland function in pregnancy.

PURPOSE: To evaluate the signs and symptoms of dry eye in healthy pregnant women and investigate the effect of pregnancy on meibomian gland loss using non-contact meibography. METHODS: Healthy pregnant women and age-matched healthy non-pregnant women were included in the study. Subjective symptoms were assessed using the Ocular Surface Disease Index (OSDI). The first and average non-invasive break-up times (first-NIBUT and avg-NIBUT, respectively) were determined, and the Schirmer test was applied. Non-contact meibography was performed. RESULTS: The study included a total of 62 women, 30 pregnant (study group) and 32 non-pregnant (control group). There was no significant difference between the groups in terms of OSDI score and the Schirmer test (p > 0.05). The mean first-NIBUT and avg-NIBUT values of the study group (13.1 ± 5.3 and 13.7 ± 4.5 s) were significantly lower than the control group (16.0 ± 2.4 and 16.4 ± 1.5 s) (p: 0.015 and p: 0.040, respectively). The mean meibomian gland losses in the upper and lower eyelids were significantly higher in the study group (16.9 ± 8.2% and 11.6 ± 10.2%) compared to the control group (9.7 ± 6.2% and 5.6 ± 4.7%) (p < 0.001 and p: 0.011, respectively). CONCLUSIONS: It is considered that loss of the meibomian glands may occur during pregnancy, and this may predispose pregnant women to evaporative dry eye. Although dry eye does not cause significant ocular surface symptoms in pregnancy, NIBUT and non-contact meibography can be considered as effective diagnostic methods for the detection of dry eye in pregnant women.

The BDNF-TrkB signaling pathway is partially involved in the neuroprotective effects of hydrogen sulfide in Parkinson's disease.

Recent studies have demonstrated that hydrogen sulfide (H2S) has a neuroprotective effect in neurodegenerative diseases. It is possible that this effect is supported by brain-derived neurotrophic factor (BDNF). Our aim is to examine the effects of H2S on neural damage in Parkinson's disease (PD) and to reveal the role of the BDNF-TrkB pathway in its possible effect. PD model was created with 1-methyl-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 breed male mice were randomly divided into six groups: control, K252a, MPTP, MPTP + K252a, MPTP + NaHS, and MPTP + NaHS + K252a. TrkB receptor antagonist K252a and sodium hydrosulfide (NaHS) as a H2S donor were administered intraperitoneally. An increase was observed in the motor behavior tests in MPTP group, but NaHS treatment shortened the time spent on the balance beam and pole tests. It was also noticed that the BDNF-pathway played a role in the shortening of this period. Mice that received NaHS were found to have less MPTP-induced cellular damage. A positive effect of BDNF was also detected in the protection of these neurons. BDNF levels in the SN were significantly increased in MPTP group, compared to control group. Tissue CBS levels decreased in the groups that received K252a, compared to MPTP group. The findings of the present study display that the BDNF-TrkB pathway partially plays a role in the protective effect of H2S in the experimental mouse model of PD. This effect is probably due to changes in intracellular signaling pathways, rather than TrkB receptor expression.

Evaluation of ocular symptoms in COVID-19 subjects in inpatient and outpatient settings.

PURPOSE: Evaluation of subtle ocular involvement and clinically significant conjunctivitis symptoms in a group of patients with COVID-19 in outpatient and inpatient settings. METHOD: Overall, 1083 patients infected with SARS-CoV-2 were recruited as subjects. Patients were divided into inpatients (group 1, n = 371) and outpatients (group 2, n = 712). Demographical and general medical data included age, sex, and comorbidities. Patients whose diagnosis was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR) were called by phone, and their chronic ocular disease, previous ocular surgery, ocular medication, contact lens wear and ocular irritation symptoms were queried during the active disease period. RESULTS: The mean age of the patients was 44.2 ± 16.5 (19-97) years; 635 (58.6%) were male, and 448 (41.4%) were female. Comorbidity, chronic ocular disease, ophthalmic medication and previous ocular surgery rates were significantly higher in group 1 (p < 0.05), while contact lens wear was not significantly different between groups. The main complaints received from patients were sore eye or burning sensation, foreign body sensation, itching and red eye and were significantly higher in group 1. Clinically significant conjunctivitis symptoms, such as red eye, ocular discharge and eyelid edema, were observed in 28 patients (2.6%), with 14 (3.8%) patients in group 1 and 14 (2%) patients in group 2. CONCLUSION: Clinically significant conjunctivitis symptoms were detected in 28 subjects in the inpatient and outpatient groups. As systemic findings of COVID-19 intensify.

Renal response to tunicamycin-induced endoplasmic reticulum stress in BDNF heterozygous mice.

BACKGROUND: The protective effects of brain-derived neurotrophic factor (BDNF) against endoplasmic reticulum (ER) stress in neuronal tissue and endometrial cells have been reported. OBJECTIVES: The aim of this study was to determine whether endogenously produced BDNF protects the kidneys against tunicamycin-induced (Tm) ER stress. MATERIAL AND METHODS: Brain-derived neurotrophic factor heterozygous knockout mice (BDNF(+/-)) and their wild-type (WT) littermates were used. The animals were divided into 4 groups: WT, BDNF(+/-), WT+Tm, and BDNF(+/-)+Tm (n = 7 in each group). After 3 days of saline or Tm injection (0.5 mg/kg; intraperitoneally (i.p.)), renal BDNF, glucose-regulated protein 78 (GRP78), and caspase-12 levels as well as serum BDNF concentration were measured with enzyme-linked immunosorbent assay (ELISA). In the kidney sections, hematoxylin & eosin (H&E) staining, GADD153 immunostaining and TUNEL staining were performed. Serum creatinine levels were measured as an indicator of renal function. RESULTS: Circulating and tissue BDNF levels were significantly lower in the BDNF(+/-) and BDNF(+/-)+Tm groups. Renal levels of GRP78 and caspase-12, apoptotic index, and GADD153 staining were significantly higher in the WT+Tm and BDNF(+/-)+Tm groups. However, apoptosis was more pronounced in the BDNF(+/-)+Tm group than in the WT+Tm group (p < 0.01). Similarly, GADD153 staining was more pronounced in the BDNF(+/-)+Tm group than in the WT+Tm group (p < 0.05). Tm caused a mild deterioration in the kidney tissue of the WT+Tm group, while general deterioration, pyknotic nuclei and swollen cells were observed in the BDNF(+/-)+Tm group. Serum creatinine concentrations were significantly higher in the WT+Tm (p < 0.05) and BDNF(+/-)+Tm (p < 0.05) groups. CONCLUSIONS: This study showed that endogenous BDNF may play a protective role in kidneys against ER stress-induced apoptosis via the suppression of GADD153. As a result, BDNF and related signaling pathways could be considered for therapeutic/protective approaches in kidney disorders.

Endoplasmic reticulum stress in the livers of BDNF heterozygous knockout mice.

Context: Involvement of endoplasmic reticulum (ER) stress and brain-derived neurotrophic factor (BDNF) in hepatic lipid metabolism has been reported previously. Objective: The effects of chronic BDNF deficiency on ER stress response in the livers were examined in this study. Methods: BDNF(+/-) mice, characterised by BDNF deficiency, and their wild-type (WT) littermates were used. The ER stress was induced by tunicamycin (Tm) (0.5 mg/kg, intraperitoneal). Animals were divided into four groups; WT, WT + Tm, BDNF(+/-), and BDNF(+/-)+Tm. Results: At the basal conditions, BDNF deficiency did not affect hepatic cell death or lipid accumulation. However, during ER stress, BDNF(+/-)+Tm group showed increased apoptosis, GADD153 immunostaining, sterol regulatory element-binding protein-1c (SREBP-1c) level, and steatosis compared to the WT + Tm group. Conclusion: Endogenous BDNF might be protective against apoptosis through GADD153 suppression and steatosis via SREBP-1c suppression during ER stress. This effect of BDNF might be clinically important for type 2 diabetes and obesity, which are related with both ER stress and BDNF deficiency.

Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model.

OBJECTIVES: Exposing to stress may be associated with increased production of reactive oxygen species (ROS). Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF) supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. MATERIALS AND METHODS: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT) and superoxide dismutase (SOD) enzymes, and the amount of malondialdehyde (MDA) were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. RESULTS: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. CONCLUSION: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain.

The relationship between oxidative stress markers and visual evoked potentials in different hypertension models.

OBJECTIVE: We aimed to define the influence of different hypertension models on lipid peroxidation markers [conjugated dienes (CD) and thiobarbituric acid-reactive substances (TBARS)], antioxidant protection [paraoxonase-1 (PON1) activity] and visual evoked potential (VEP) changes in rats. METHODS: The study was designed as four different hypertension models. Rats (n=84) were divided equally into six groups: Control group (C), Sham operated (Sham), Two kidney-one clip (2K-1C), One kidney-one clip (1K-1C), Deoxycorticosterone acetate (DOCA) and N-omega-nitro-L-arginine-methyl ester (L-NAME). Brain TBARS, serum lipids (total and lipoprotein bound cholesterols and triglycerides) CD and TBARS levels and PON1 activity were assayed. Comparisons were performed using ANOVA or Wilcoxon/Kruskal-Wallis tests. Pearson correlation and linear regression analysis were used to evaluate associations of independent predictors with hypertension. RESULTS: Mean arterial pressure, brain and serum lipid peroxidation markers, VEP latencies were significantly higher in four hypertensive groups compared with control and sham groups (p<0.05). Compared with controls, PON1 activity was decreased in DOCA, 1K1C and L-NAME groups (p<0.05). Serum PON1 activity was negatively correlated with lipid peroxidation markers and VEPs. In terms of VEP's records linear regression analysis showed that changes in N2 (B=1.51±0.34; p<0.001), P1 (B=-1.71±0.28; p<0.001), P3 (B=0.54±0.14; p<0.001), serum TBARS levels (B=0.94±0.24; p<0.001) and PON1 activity (B=0.05±0.02; p<0.01) were independently associated with elevated blood pressure. CONCLUSION: Lipid peroxidation measured in serum and brain was associated with increased electrophysiological alterations recorded as VEPs. This study might suggest that serum PON1 activity may be protective against brain and serum lipid peroxidation as well as electrophysiological alterations in the brain in different hypertension models.

Docosahexaenoic acid provides protective mechanism in bilaterally MPTP-lesioned rat model of Parkinson's disease.

Docosahexaenoic acid (DHA), a major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain, is essential for normal cellular function. Neurodegenerative disorders such as Parkinson's disease (PD) often exhibit significant declines in PUFAs. The aim of this study was to observe the effects of DHA supplementation in an experimental rat model of PD created with '1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine' (MPTP). Adult male Wistar rats were divided into four groups: (1) Control; (2) DHA-treated; (3) MPTP-induced; and (4) MPTP-induced + DHA-treated. Motor activity was investigated using the 'vertical pole' and 'vertical wire' tests. The dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase (TH)-immunopositive cells in substantia nigra (SN). Immunoreactivities of Bcl-2, Akt and phosphorylated-Akt (p-Akt) in SN were evaluated by immunohistochemistry. MPTP-induced animals exhibited decreased locomotor activity, motor coordination and loss of equilibrium. Diminished Parkinsonism symptoms and decreased dopaminergic neuron death were detected in the MPTP-induced + DHA-treated group compared to the MPTP-induced group. Moderate decreases in Akt staining were found in the MPTP-induced and MPTP-induced + DHA-treated groups compared to controls. p-Akt immunoreactivity decreased dramatically in the MPTP-induced group compared to the control; however, it was increased in the MPTP-induced + DHA-treated group compared to the MPTP-induced group. The staining intensity for Bcl-2 decreased prominently in the MPTP-induced group compared to the control, while it was stronger in the MPTP-induced + DHA-treated group compared to the MPTP-induced group. In conclusion, DHA significantly protects dopaminergic neurons against cell death in an experimental PD model. Akt/p-Akt and Bcl-2 pathways are related to this protective effect of DHA in experimental PD.

The effect of sodium metabisulphite on active avoidance performance in hypercholesterolemic rats.

The purpose of this study was to investigate the effects of hypercholesterolemia and sulphite on active avoidance learning. Male Wistar rats were divided into eight groups as follows: Control (C), Sulphite (S), Vitamin E (E), Sulphite + Vitamin E (SE), Hypercholesterolemia (H), Hypercholesterolemia + Sulphite (HS), Hypercholesterolemia + Vitamin E (HE), and Hypercholesterolemia + Sulphite + Vitamin E (HSE). At the end of the experimental period, the serum cholesterol level (mean ± SD) was significantly higher in H group (111.5 ± 11.11 mg dL(-1) ) as compared to C group (63.5 ± 4.9 mg dL(-1) ). Levels of thiobarbituric acid reactive substances (TBARS) were increased in HS group as compared to C, H, and S groups. Vitamin E reduced TBARS levels in HSE group compared with HS group. Active avoidance results indicated that hypercholesterolemia was associated with learning impairment. Our data clearly revealed that the combination of hypercholesterolemia and sulphite results in exaggerated impairment of active avoidance. Vitamin E improved active avoidance in HSE group compared with HS group. Therefore, the synergistic effect of hypercholesterolemia and sulphite may be associated with a considerable health risk.

The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson's disease.

This study aimed to investigate the effects of docosahexaenoic acid (DHA) on the oxidative stress that occurs in an experimental mouse model of Parkinson's disease (PD). An experimental model of PD was created by four intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 × 20 mg/kg, at 12h intervals). Docosahexaenoic acid was given daily by gavage for 4 weeks (36 mg/kg/day). The motor activity of the mice was evaluated via the pole test, and the dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase (TH)-immunopositive cells. The activity of antioxidant enzymes in the brain were determined by spectrophotometric assays and the concentration of thiobarbituric acid-reactive substances (TBARS) were measured as an index of oxidative damage. The number of apoptotic dopaminergic cells significantly increased in MPTP-treated mice compared to controls. Although DHA significantly diminished the number of cell deaths in MPTP-treated mice, it did not improve the decreased motor activity observed in the experimental PD model. Docosahexaenoic acid significantly diminished the amount of cell death in the MPTP+DHA group as compared to the MPTP group. TBARS levels in the brain were significantly increased following MPTP treatment. Glutathione peroxidase (GPx) and catalase (CAT) activities of brain were unaltered in all groups. The activity of brain superoxide dismutase (SOD) was decreased in the MPTP-treated group compared to the control group, but DHA treatment did not have an effect on SOD activity in the MPTP+DHA group. Our current data show that DHA treatment exerts neuroprotective actions on an experimental mouse model of PD. There was a decrease tendency in brain lipid oxidation of MPTP mice but it did not significantly.

The effect of sodium metabisulfite on visual evoked potentials in rats with hypercholesterolemia.

This study aimed to investigate the effects of hypercholesterolemia on visual evoked potentials (VEPs) and sulfite additional effects. Rats were assigned as follows: control (C), sulfite (S), hypercholesterolemia (H), vitamin E (E), sulfite + vitamin E (SE), hypercholesterolemia + sulfite (HS), hypercholesterolemia + vitamin E (HE), and hypercholesterolemia + sulfite + vitamin E (HSE). Hypercholesterolemic diet led significant increase in plasma cholesterol levels of rats. Brain thiobarbituric acid reactive substances (TBARS) levels were significantly increased in S, E, SE, HE and HSE groups compared with C. TBARS levels were increased in HE and HSE groups as compared to HS group. Nitrite levels were decreased in S, SE, H, HS and HSE groups compared with C. Nitrite level was notably increased in the HE group compared with H group. Sulfite exposure prolonged N1 and P3 latencies of VEP in group S compared with C. Prolonged VEP latencies by sulfite were significantly decreased by vitamin E in SE group. Cholesterol rich diet increased VEP latencies in comparison with control latencies. Sulfite gave rise to an additional increase in P3 latency in HS group compared with H group. Vitamin E-treated animals had notably shortened latencies of VEP components in HE and HSE groups according to the H and HS groups, respectively.

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder marked by cell death in the Substantia nigra (SN). Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain and is required for normal cellular function. Glial cell line derived neurotrophic factor (GDNF) and neurturin (NTN) are very potent trophic factors for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF and NTN by investigating their immunostaining levels after administration of DHA in a model of PD. For this reason we hypothesized that DHA administration of PD might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic neurodegeneration was used to create the experimental Parkinsonism model. Rats were divided into; control, DHA-treated (DHA), MPTP-induced (MPTP), MPTP-induced+DHA-treated (MPTP+DHA) groups. Dopaminergic neuron numbers were clearly decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this, DHA administration protected dopaminergic neurons as shown by tyrosine hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN immunoreactions in dopaminergic neurons were higher than that of the MPTP group. In conclusion, the characterization of GDNF and NTN will certainly help elucidate the mechanism of DHA action, and lead to better strategies for the use of DHA to treat neurodegenerative diseases.

The effect of diabetes mellitus on active avoidance learning in rats: the role of nitric oxide.

BACKGROUND: Growing data report memory and other cognitive problems among individuals with diabetes mellitus. Nitric oxide may play a key role in many physiological and pathological situations. The aim was to investigate the role of NO in diabetes-induced changes in learning and lipid peroxidation. MATERIAL/METHODS: Six groups of 10 rats each were formed: control (C), diabetic (D), control+L-arginine (CA), diabetic+L-arginine (DA), control+L-NAME (CN), and diabetic+L-NAME (DN) groups. Experimental diabetes mellitus was induced by injection of streptozotocin (60 mg/kg body weight). 160 mg/kg/day L-arginine or 10 mg/kg/day L-NAME were injected intraperitoneally to the relevant groups for eight weeks. Active avoidance behavior was studied in the middle of the eighth week using an automated shuttle box. Brain and hippocampal nitrite levels were measured by a fluorometric method. TBARS levels were measured fluorometrically using 1,1,3,3-tetramethoxypropane as a standard. RESULTS: The active avoidance training indicated that diabetes was associated with learning impairment. Administration of L-NAME and L-arginine significantly impaired active avoidance performance compared with the control group. They also decreased glucose level in group DA compared with the diabetic group. Brain nitrite level was significantly different in the diabetic group; hippocampus nitrite level tended to be lower in the L-NAME groups than the diabetic and control groups, although L-arginine increased hippocampal and brain nitrite values in the CA group compared with control groups. Brain and hippocampal TBARS levels were significantly higher in diabetic than in control rats. CONCLUSIONS: Imbalance related to nitric oxide production may contribute to cognitive dysfunction in diabetes mellitus.

Exercise improves visual deficits tested by visual evoked potentials in streptozotocin-induced diabetic rats.

Visual evoked potentials (VEP) can be used as an objective non-invasive method to study the electrical activity of the visual system. Latency and amplitude measurements of VEP demonstrated that diabetes mellitus has been associated with increases in the latencies whereas the amplitude measurements revealed contradictory results. Although physical exercise has been reported to reduce the complications of diabetes mellitus, the effect of exercise on the visual system remains unknown. We investigated the effects of long-term moderate physical exercise on VEP in streptozotocin (STZ)-diabetic rats. We also measured brain thiobarbituric acid-reactive substances (TBARS) to explore the possible contribution of lipid peroxidation on the visual system. Animals were divided into four groups: control (C), control exercise (CE), diabetic (D) and diabetic exercise (DE) groups. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Three days after the confirmation of diabetes, DE and CE groups were trained by running on a motor-driven treadmill with a progressive eight-week programme. The animals began running at 10 m/min, 0 degrees slope, 10 min/day and reached a level of 28 m/min, 6 degrees slope, 60 min/day by week 8. TBARS were elevated and VEP latencies were delayed in diabetic rats, indicating diabetes-induced defects in the optic pathway. These prolonged latencies were restored by exercise training. VEP amplitudes of the DE group were found unaltered with the exception of a decrement in P(2)N(2) which represents an early component of VEP, suggesting that exercise improves visual system defects in diabetic animals at different levels of the optic pathway.

Effect of docosahexaenoic acid on macrophage functions of rats.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid which has been demonstrated to exhibit anti-inflammatory effects. The objective of this study was to determine the effect of DHA on phagocytic and chemotactic activities of peritoneal macrophages obtained from rats. DHA was dissolved in 1 ml of corn oil at dose of 36 mg/kg/day and given via oral gavage for 4 weeks. Control rats received 1 ml/day corn oil as vehicle. At the end of the treatment period, peritoneal macrophages were isolated and chemotactic and phagocytic activities were assayed. Chemotactic and phagocytic activities were reduced in rats fed with DHA. These results demonstrated the effect of DHA in modulating immune activities of rat peritoneal macrophages.

Beneficial effects of docosahexaenoic acid on active avoidance performance in 1K-1C hypertensive rats.

The present study evaluated the role of chronic docosahexaenoic acid (DHA) supplementation on active avoidance learning task performance in experimental hypertension. Male Wistar rats were randomly divided into five experimental groups as follows: control, sham, DHA treated, 1K-1C hypertensive, and 1K-1C hypertensive+DHA treated. Hypertension was induced in 1K-1C rats via placing a silver clip (0.20-mm ID) around the left renal artery following a right uninephrectomy. DHA (36 mg/kg/day) was given to the treatment groups for 60 days by gastric gavage. Arterial blood pressure was measured by using the tail-cuff method. Active avoidance responses were determined by an automated shuttle-box. In brain (cerebrum) and hippocampus tissues, thiobarbituric acid reactive substances (TBARS) and nitrite levels were measured by fluorometric methods. DHA supplementation decreased blood pressure in hypertensive rats. Data from active avoidance training indicated that performance of active avoidance learning tasks were significantly impaired in 1K-1C hypertensive rats, but was completely restored by DHA supplementation. Increased cerebrum TBARS levels in 1K-1C rats were abolished by DHA administration. Cerebrum nitrite levels were lower in the DHA, 1K-1C and 1K-1C+DHA treated groups compared to controls. Hippocampus nitrite levels were lower in DHA treated and 1K-1C hypertensive rats compared to controls and higher in 1K-1C+DHA treated rats compared to the 1K-1C group. Our data indicates that DHA supplementation improves the performance of active avoidance learning tasks which is impaired in experimental hypertension. These affirmative changes might be due to a DHA-induced decrease in lipid peroxidation which may in turn limit the consumption of nitric oxide (NO) which promotes active avoidance learning.

The role of docosahexaenoic acid on visual evoked potentials in one kidney-one clip hypertension.

PURPOSE: To investigate the effects of polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) on visual evoked potentials (VEPs) in a one kidney-one clip (1K-1C) hypertension model in rats. METHODS: Five experimental groups were formed: a control group, a sham group, a group supplemented with DHA, a 1K-1C group, and a 1K-1C + DHA group. The DHA groups were treated for 60 days. In the 1K-1C groups, the right kidney was removed and a silver clip with a 0.2-mm gap was placed on the left renal artery. RESULTS: The DHA-supplemented rats had lower blood pressure than their respective controls (p < 0.01). The increased brain and retina thiobarbituric acid reactive substances (TBARS) levels in hypertensive rats were abolished by DHA administration. The brain nitrite levels were lower in the DHA, 1K-1C and 1K-1C + DHA groups compared with the control group (p < 0.01), and the retina nitrite level was higher in the 1K-1C + DHA group compared with the DHA and 1K-1C groups (p < 0.01). There was an improvement of P(2), N(2) and P(3) components following DHA supplementation in 1K-1C hypertensive rats compared with the 1K-1C group. CONCLUSION: The present study suggests that DHA supplementation has the potential to prevent VEP changes caused by an experimental model of hypertension. This state might be related to the lipid peroxidation lowering effect of DHA.

Visual evoked potentials in normal and sulfite oxidase deficient rats exposed to ingested sulfite.

Sulfite oxidase (SOX) is an essential enzyme in the pathway of the oxidative degradation of sulfur amino acids, and protects cells from sulfite (SO(3)(2-)) toxicity. Rats do not mimic responses seen in human, because of their relatively high SOX activity levels. Therefore, the present study used SOX deficient rats since they are a more appropriate model for studying sulfite toxicity. The aim of the study was to investigate the effect of sulfite exposure on visual evoked potentials (VEPs) and thiobarbituric acid reactive substances (TBARS) in normal and sulfite oxidase deficient rats. Rats were assigned to six groups (n=10 rats/group) as follows; control (C), sulfite (S), sulfite+vitamin E (SE), deficient (D), deficient+sulfite (DS) and deficient+sulfite+vitamin E (DSE). Sulfite oxidase deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten (W). Sulfite (25img/kg) was administered to the animals via their drinking water. At the end of the experimental period, flash visual evoked potentials were recorded, and TBARS, hepatic sulfite oxidase levels and plasma S-sulphonate concentrations were determined. Sulfite treatment caused a significant delay in P1, N1P2, and P3 components of VEPs in the S and DS groups compared with the C group. These prolonged mean latencies of VEP components were reversed by vitamin E treatment in SE and DSE groups. In addition, the mean latencies of P1 and P3 components were increased in SOX deficient groups compared with the C group. Lipid peroxidation was increased in the brain in S, D, DS and DSE groups compared with the control group. There were also significant increases in the retina TBARS levels of S and DS groups. Vitamin E caused a significant decrease in brain and retina TBARS levels of SE and DSE groups with respect to their corresponding controls. However, there were no important changes in amplitudes of other groups. In conclusion, our results showed that sulfite treatment caused an increase in the lipid peroxidation process that was accompanied by changes in VEPs. Furthermore, sulfite exposure resulted in greater lipid peroxidation and more electrophysiological alterations in the SOX deficient rats than in the control rats. Additionally, the reduction of all VEP latencies in the DSE group with respect to the DS group clearly indicated that vitamin E has the potential to prevent sulfite induced-VEP changes arising from dysfunction of the SOX enzyme.

Effect of sulfite on cognitive function in normal and sulfite oxidase deficient rats.

Sulfites, which are commonly used as preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. 1.8.3.1). The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and SOX-deficient rats. For this purpose, male albino rats used in this study were divided into eight groups such as control group (C), sulfite group (25 mg/kg) (S), vitamin E group (50 mg/kg) (E), sulfite (25 mg/kg)+vitamin E group (50 mg/kg) (SE), SOX-deficient group (D), deficient+vitamin E group (50 mg/kg) (DE), deficient+sulfite group (25 mg/kg) (DS) and deficient+sulfite (25 mg/kg)+vitamin E group (50 mg/kg) (DSE). Sulfite-induced impairment of active avoidance learning in SOX-deficient rats but not in normal rats. Sulfite had no effect on hippocampus TBARS levels in SOX normal groups. In SOX-deficient rats, TBARS levels were found to be significantly increased with sulfite exposure. Vitamin E reversed the observed detrimental effects of sulfite in the SOX-deficient rats on their hippocampal TBARS but not on their active avoidance learning. In conclusion, sulfite has neurotoxic effects in sulfite oxidase deficient rats, but this effect may not depend on oxidative stress.