Detection of borderline dosage of malathion intoxication in a rat's brain.

OBJECTIVE: Humans and other animals are liable to expose to low doses of malathion (MAL). However, experimental studies on its toxic threshold dose and toxic low-dose effects have not been conducted. The aims of this study were to detect the initiation of the toxic effects of sub-acute low doses (2.5, 5, and 10 mg/kg) of MAL by immunohistochemical and biochemical parameters in rat brain. MATERIALS AND METHODS: Twenty-eight rats were randomly assigned into four groups (n=7) including control and three different amounts of MAL-exposed groups (2.5, 5, and 10 mg/kg). RESULTS: On immunohistochemical examination, the number of caspase-3-positive cells in all MAL-exposed groups was significantly higher than in the control group. Consistent with this, the total antioxidant capacity, total oxidant status, and the levels of superoxide dismutase, malondialdehyde, and paraoxanase activity were significantly different in the 5 and 10 mg/kg MAL-exposed groups compared with the control group. Additionally, the total oxidant status and malondialdehyde levels were significantly higher in the 5 and 10 mg/kg MAL-exposed groups compared with those in the 2.5 mg/kg MAL-exposed group. CONCLUSIONS: Our results indicate that over 5 mg/kg MAL exposure may result in dose-dependent oxidative stress, increased caspase-3 activity, and launching to the toxic effects in rat brain.

Assesment the role of oxidative stress and efficacy of caffeic acid phenethyl ester (CAPE) on neurotoxicity induced by isoniazid and ethambutol in a rat model.

OBJECTIVE: The aim of this study were to investigate a role of oxidative stress and the therapeutic efficacy of caffeic acid phenethyl ester (CAPE) in the pathogenesis of neurotoxicity induced by isoniazid and etambutol in a rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly divided into eight experimental groups: control, INH, ETM, INH+ETM, INH+CAPE, ETM+CAPE, INH+ETM+CAPE, and CAPE treatment group, with ten animals in each group. INH and ETM doses were given orally within tap water for 30 days. CAPE was administered into relevant groups intraperitoneally for 30 days. Brain tissue and sciatic nerve were removed for biochemical and histopathological investigation. RESULTS: In the INH, ETM, and INH+ETM groups, malondialdehyde (MDA) and total oxidant status (TOS) levels were significantly higher than those of the control group (p < 0.05). Also, in these groups, brain total antioxidant capacity (TAC) levels, and superoxide dismutase (SOD) and PON-1 activities were decreased compared with the control group (p < 0.05). By a CAPE supplement within INH and ETM groups, there was a significant decrease in MDA and TOS (p < 0.05). In addition to a significant increase in TAC levels, and SOD and PON-1 activities both in brain and sciatic nerve tissues (p < 0.05). CONCLUSIONS: CAPE may protect against INH- and ETM-induced neurotoxicity in rat brain and sciatic nerve.

Neuroprotective effects of carvacrol and pomegranate against methotrexate-induced toxicity in rats.

BACKGROUND: Studies related to the use of various antioxidant and anti-inflammatory drugs to decrease the toxic side effects related to MTX have been carried out. However, since no medicine providing full protection against the side effects of MTX has been discovered, the discovery of new agents is required. AIM: The aim of this study was to determine whether methotrexate (MTX) causes oxidative stress and an inflammatory response in sciatic nerve, as well as whether carvacrol (CAR) and pomegranate (POM) have protective effects against the resulting oxidative stress and inflammatory response. MATERIALS AND METHODS: 32 adult male Wistar albino rats were used in the study. The animals were divided into 4 groups: Group C: the rats were not given any medication; Group MTX: On study day 2, the rats were given a single dose of 20 mg/kg MTX, administered intraperitoneally; Group MTX+CAR: On study day one, the rats were administered a single dose of 73 mg/kg CAR intraperitoneally. On study day two, a single dose of 20 mg/kg MTX was administered intraperitoneally; Group MTX+POM: For seven days starting from the study day one, rats were given 225 mg/kg POM extract once a day through orogastric gavage. On study day two, a single dose of 20 mg/kg MTX was administered intraperitoneally. All animals were sacrificed on the day eight. TOS, TAS, MDA, TNF-α and IL-1ß levels were evaluated in the sciatic nerve tissue. RESULTS: In comparison to the control group, a decrease in TAS levels and an increase in TOS, MDA, IL-1ß and TNF-α levels were detected in the MTX group. Compared to the MTX group, the MTX+CAR group had a significant increase in TAS level and significant decreases in TOS, MDA, IL-1ß and TNF-α levels. In comparison to the MTX group, the MTX+POM group had a significant decrease in MDA, IL-1ß and TNF-α levels. When the MTX+CAR and MTX+POM groups were compared, the TNF-α level measured was lower in the MTX+CAR group. CONCLUSIONS: In this work, we have shown that MTX causes a significant oxidative stress and inflammatory response in rats' sciatic nerve tissue and that CAR had an antioxidant effect in this system. Furthermore, we have proven, for the first time, that both CAR and POM decreased the pro-inflammatory response.

Effects of melatonin on behavioral changes of neonatal rats in a model of cortical dysplasia.

BACKGROUND: Cortical dysplasia (CD) is associated with several behavioral disorders in both the pediatric and the adult population. The effect of melatonin on behavioral disorders in rats generated CD has not been investigated so far. AIM: To investigate the effects of melatonin administration on activity and anxietic behavior of neonatal rats in a model of CD. MATERIALS AND METHODS: Newborn Sprague-Dawley rats (n=21) were randomized into three groups. On postnatal day 1, one freeze lesion was carried out in 14 rats between bregma and lambda to create a CD model. Another group of neonatal rats served as control group (n=7). Those 14 rats were either administered melatonin (n=7) or vehicle solution (n=7). Melatonin treatment (4 mg/kg/day, i.p.) was initiated ten days after induction of cold injury and continued for three weeks. Animal activity and anxiety were analyzed by using open field and elevated plus maze tests 24h after the last melatonin administration (day 32) in a blind manner. RESULTS: It was observed that CD induced animals spent significantly less time in the open field area when compared to the other groups (p < 0.01). Additionally, the time spent in the open field area was significantly elevated in the melatonin-treated animals compared to both the control and the CD groups (p < 0.01). Accordingly, anxiety scores in the CD group was significantly increased (p < 0.01), and this effect could be reversed by administration of melatonin. CONCLUSIONS: Melatonin exerts protective behavioral effects against cortical dysplasia in newborn rats. Further clinical investigations may prove melatonin as a useful therapeutic adjunct to prevent from possible behavioural damages of cortical dysplasia.

Effects of estrogen, estrogen/progesteron combination and genistein treatments on oxidant/antioxidant status in the brain of ovariectomized rats.

INTRODUCTION: The aim of this study was to investigate the antioxidative effects of estradiol (E), E plus progesteron (P) combination (E/P) and genistein (G) treatment in the brain of ovariectomized (OVX) rats. MATERIALS AND METHODS: Adult female Sprague-Dawley rats were divided into five groups, with each group including ten rats. Rats were anesthetized and bilateral ovariectomy was performed under general anaesthesia in all groups except for the sham operation group. Groups included: Sham-operated, control (OVX), estrogen treated group (OVX+ E), E/P combination group (OVX+E/P) and G treated group (OVX+G). Treatments were applied for 8 weeks. The total anti-oxidant status (TAS), total oxidant status (TOS), nitric oxide level (NO), glutathione peroxidase activity (GSH-Px) and oxidative stress index (OSI) were analysed in the brain tissue of rats from each treatment category. RESULTS: Ovariectomy lead to an increase in brain TOS and OSI levels compared to the sham group (p < 0.05). Also, ovariectomy resulted in a decrease in brain TAS levels compared to the sham group that approached statistical significance (p = 0.078). Significant decreases in TOS, OSI, GSH-Px and a significant increases in TAS and NO levels were observed in the E-treatment group compared to the control group (p < 0.001). The E/P combination group exhibited a significantly decreased TOS and OSI and significantly increased TAS and NO levels relative to the control group (p < 0.05). Genistein treatment resulted in a significant decrease in TOS and OSI compared to the control group (p < 0.05). CONCLUSIONS: Oxidative stress markers increase in the brain tissue of OVX rats. Conversely, estradiol, E/P and G supplementation decreases oxidative stress markers and increases antioxidant activity. Using G may prevent neural pathologies result in menopause-related oxidative stress.

Cerebral venous sinus thrombosis: an analyses of 47 patients.

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is an extremely rare disease and its early treatment is important for decreasing the morbidity and mortality. In present study, it was investigated to clinical and etiological factors, localization features, treatment, and prognosis of patients with CVST. PATIENTS AND METHODS: The study group included CVST cases who were followed up between January 2008 and June 2010. Demographical, clinical, radiological, etiological and prognostic characteristics of 47 patients with CVST were retrospectively investigated. RESULTS: Presentation complaints of the patients were as follows in order: acute and/or sub-acute headache (80.8%), impaired consciousness (25.5%), ear complaints (21.3%), paresis (19.1%) and epileptic seizures (14.9%). Chronic daily headache without any signs of neurological deficit was found in 10.6% of cases. Neurologic examinations of 40.4% of the CSVT patients were found to be normal. The most frequently found etiological factors were as follows: MTHFR gene mutation (25.5%), local infections due to chronic otitis complications (21.3%), puerperium (17%), pregnancy (12.8%), lupus anticoagulant positivity (12.8%). The sigmoid sinus was found to be involved in 35 patients (74.5%), the transverse sinus in 29 (61.7%) and superior sagittal sinus in 21 (44.7%). Impaired consciousness (p = 0.046), hemorrhagic infarct (p = 0.017), acute onset (p = 0.026), and presence of hemiparesis (p = 0.019) were found to be associated with increased mortality. CONCLUSIONS: New onset sub-acute or chronic headache may be the only neurologic complaint of CVST patients. Early diagnosis and anticoagulant treatment may decrease mortality and/or morbidity rates related with CVST in these patients.

Hydroxycloroquine-induced oxidative stress on sciatic nerve and muscle tissue of rats: a stereological and biochemical study.

The aim of this study was to investigate the role of hydroxychloroquine (HCQ)-induced oxidative stress on sciatic nerve and muscle tissues of rats. The oxidant/antioxidant parameters in the sciatic nerve and muscle tissues were analyzed, and stereological analysis of the sciatic nerve was performed. Levels of malondialdehyde and nitric oxide in the tissues were significantly higher in the HCQ group than in the control group (p < 0.05). In addition, activities of superoxide dismutase and glutathione peroxidase were found to be significantly higher in the HCQ group than the control group (p < 0.05). There were significant decreases in nerve fiber diameter and myelin sheet thickness in the HCQ group compared with the control group (p < 0.05). These results revealed that HCQ might increase oxidative stress on sciatic nerve and muscle tissues of rats, which may correlate with axonal atrophy in sciatic nerves.

Serum cytokine and pro-brain natriuretic peptide (BNP) levels in patients with migraine.

OBJECTIVE: Although migraine has been related with an increased risk for ischemic stroke and cardiovascular events, there is insufficient data for role of pro-brain natriuretic peptide (pro-BNP) in migraine. In present case-control study, serum levels of pro-inflammatory (TNF-alpha, IL-1beta and IL-6) and anti-inflammatory cytokines (IL-2, and IL-10) of migraine patients were investigated to determine the role of cytokines and pro-BNP in migraine. PATIENTS AND METHODS: Sixty-four consecutive newly diagnosed migraine patients and 34 healthy controls were enrolled. Serum TNF-alpha, IL-1beta, IL-2, IL-6, IL-10 and pro-BNP levels were measured by using a chemiluminescence assay. RESULTS: Migraine patients had significantly higher concentrations of IL-1beta and IL-6 compared with the healthy controls (for IL-1beta; 5.73 +/- 1.44 vs. 4.90 +/- 1.40 pg/mL, respectively, p = 0.006; for IL-6; 3.1 +/- 1.44 vs. 2.40 +/- 0.22 pg/mL, respectively, p = 0.007). The mean IL-10 levels were found to be significantly lower in migraine patients (3.38 +/- 2.93 pg/mL) than controls (6.76 +/- 1.48 pg/mL) (p = 0.007). There were no differences in TNF-alpha (27.2 +/- 48.1 vs. 15.4 +/- 0.7) and IL-2 (1017 +/- 661 vs. 1153 +/- 228) levels between patients with migraine and healthy controls. Migraine patients had higher concentrations of pro-BNP compared with healthy controls (27.0 +/- 28.0 versus 13.2 +/- 8.6, p = 0.006). CONCLUSIONS: Migraine patients have higher serum IL-1beta and IL-6 levels, and lower IL-10 levels than healthy subjects. These findings support that cytokines may be related to neurogenic inflammation in the pathogenesis of migraine. Also, increased pro-BNP may indicate to preclinical cardiac involvement in patients with migraine.

Sensitivity and specificity of terminal latency index and residual latency in the diagnosis of carpal tunnel syndrome.

OBJECTIVES: Traditionally, nerve conduction study (NCS) are used to diagnose carpal tunnel syndrome (CTS). However, no NCS has the sufficient sensitivity or specificity values to diagnose CTS by itself. Median terminal latency index (mTLI) and median residual latency (mRL) are parameters that calculated to identify abnormalities in distal segments of the median motor nerve. There are few studies on mTLI and mRL in the diagnosis of CTS. The objective of this study was to examine the sensitivity and specificity of mTLI and mRL together with NCS in the diagnosis of CTS. PATIENTS AND METHODS AND RESULTS: The diagnostic sensitivity of mTLI and mRL were calculated and compared with the conventional NCS. Sensitivity values of electrophysiological findings were as follows: median distal sensory latency (mDSL) 91.5%, fourth finger median-ulnar sensory (M4-U4) latency difference 91.5%, mTLI 90.1%, median sensory nerve conduction velocity (mSNCV) 87.4%, and median motor distal latency (mMDL) 68.6%. Specificity values of electrophysiological findings in those with carpal tunnel syndrome were mSNCV 98.6%, mMNCV (median motor nerve conduction velocity) 98.6%, median motor wrist muscle action potential amplitude 98.6%, median sensory nerve action potential amplitude 97.4%, mSDL 97.3% and M4-U4 (fourth finger median-ulnar sensory peak latency difference) latency difference 97.3%. In all CTS patients with long mMDL values, mTLI was found to be lower, however in 22 CTS patients (22.6%) with normal mMDL, mTLI was also found to be lower. Compared with mMDL, the sensitivity of mTLI in the diagnosis of CTS was found to be higher but its specificity was lower. No differences were found in the sensitivity and specificity of mRL and mMDL. The electrophysiological findings with the highest sensitivity and specificity in diagnosing CTS among conventional NCS were mSDL, M4-U4 peak latency difference and mSNCV. CONCLUSIONS: It was concluded that mTLI and mSDL can complete each other in the detection of abnormalities of sensory and motor fibres in the diagnosis of CTS.

Caffeic acid phenethyl ester modulates methotrexate-induced oxidative stress in testes of rat.

The aim of this study was to investigate the possible protective role of caffeic acid phenethyl ester on testicular toxicity of methotrexate in rats. Nineteen male rats were divided into three groups as follows: group I, control; group II, methotrexate-treated; group III, methotrexate + caffeic acid phenethyl ester-treated. In the second day of experiment, a single dose of methotrexate was intraperitoneally administered to groups II and III, although a daily single dose of caffeic acid phenethyl ester was intraperitoneally administered to group III for 7 days. At the end of the experiment, the testes of the animals were removed and weighed. In the tissue, the level of lipid peroxidation as malondialdehyde and activities of superoxide dismutase were higher in the methotrexate group than in the control group. Lipid peroxidation levels and superoxide dismutase activities were decreased in caffeic acid phenethyl ester + methotrexate group compared with methotrexate group. The activities of catalase in the methotrexate group decreased insignificantly although its activities were significantly increased by caffeic acid phenethyl ester administration. The activity of glutathione peroxidase did not change in the groups. There was significant difference in body weight between control and methotrexate-induced groups. In conclusion, the administration of methotrexate causes elevation of oxidative stress although treatment with caffeic acid phenethyl ester has protective effects on the oxidative stress in testes.