Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats.

AIM: We aimed to investigate the possible cardioprotective effects of paricalcitol (PR), its vitamin D receptor agonist, and vitamin D3 (VIT-D3) on an experimental model of doxorubicin (DX) cardiotoxicity by 99mTc-PYP scintigraphy, electrocardiographic (ECG) and biochemical methods. METHOD: Forty-two male Wistar/Albino rats (250‒300 g; aged 10‒12 weeks) were randomly separated into six groups, namely into control (CN), doxorubicin (DX), paricalcitol (PR), vitamin D3 (VIT-D3), paricalcitol + doxorubicin (PR+DX), and vitamin D3 + doxorubicin (VIT-D3+DX) groups. Cardiotoxicity was induced by three doses of DX (18 mg/kg, i.p.) at 24-hour intervals on days 18, 19 and 20. PR (0.5 ug/ kg, i.p) and VIT-D3 (5,000 IU/kg, i.p) were injected for 20 days before and after the application of DX (18 mg/kg, i.p.). On day 21 of the experiment, biochemical parameters [tumor necrosis factor TNF-alpha (TNF-α); interleukin-6 (IL-6), nitric oxide (NO), and cardiac troponin T (cTnT)], as well as ECG and scintigraphic (99mTc-PYP) features were assessed. RESULTS: Compared to CN, DX significantly raised TNF-α, IL-6, and NO in heart tissue, cTnT in serum, 99mTc-PYP uptake in the myocardium, and ECG parameters, specifically QRS complex duration, QT interval duration, and ST-segment amplitude, while also reducing heart rate (p<0.001). Pretreatment with PR and VIT-D3 mitigated these abnormalities produced by DX in the heart (p<0.001). CONCLUSION: Results show that vitamin D receptor agonist paricalcitol and vitamin D protect against DX-induced cardiotoxicity through anti-inflammatory and antioxidant effects (Fig. 4, Ref. 59). Text in PDF www.elis.sk Keywords: paricalcitol, doxorubicin, vitamin D, ECG, 99mTc-PYP scintigraphy, cardiotoxicity, inflammation.

The electrophysiological and behavioral evaluation of the peptide hemopressin and cannabinoid CB1 receptor agonist and antagonist in pentylenetetrazol model of epilepsy in rats.

This study endeavoured to assess the effect of hemopressin (Hp), a nano peptide obtained from the alpha chain of hemoglobin, on chronic epileptic activity and its potential correlation with cannabinoid receptor type 1 (CB1). Male Wistar albino rats (230-260 g) were used. The kindling process was conducted by administering a sub-convulsant dose of pentylenetetrazol (PTZ) (35 mg/kg, i.p) three times a week for a maximum of 10 weeks. Tripolar electrodes and external cannula guides for intracerebroventricular (i.c.v) injections were surgically implanted in the skulls of kindled rats. On the day of the experiment, doses of Hp, AM-251, and ACEA were administered prior to the PTZ injections. Electroencephalography recordings and behavioural observations were conducted simultaneously for 30 min after the PTZ injection. The administration of Hp (0.6 µg, i.c.v) resulted in a decrease in epileptic activity. The CB1 receptor agonist ACEA (7.5 µg, i.c.v) showed an anticonvulsant effect, but the CB1 receptor antagonist AM-251 (0.5 µg, i.c.v) displayed a proconvulsant effect. The co-administration of Hp (0.6 µg, i.c.v) and ACEA (7.5 µg, i.c.v) and of Hp (0.6 µg, i.c.v) and AM-251 (0.5 µg, i.c.v) produced an anticonvulsant effect. However, when AM-251 was administered prior to Hp, it produced a proconvulsant impact that overrode Hp's intended anticonvulsant effect. Interestingly, the co-administration of Hp (0.03 µg) + AM-251 (0.125 µg) unexpectedly exhibited an anticonvulsant effect. Electrophysiological and behavioural evaluations demonstrated the anticonvulsant effect of Hp in the present model, highlighting the possibility that Hp may act as an agonist for the CB1 receptor.

The effect of quercetin on absence epilepsy in WAG/Rij rats.

AIM: In the present study, the effect of quercetin, a powerful antioxidant flavonoid, on genetic absence epilepsy was studied in WAG/Rij rats. MATERIAL AND METHOD: Tripolar electrodes were implanted into WAG/Rij rats. Basal electrocorticography (ECoG) was recorded following a recovery period. After basal ECoG recording, different doses of quercetin (QRC) (25, 50 and 100 mg/kg) were injected intraperitoneally (i.p.) for 30 days. ECoG recording was continued for 31 days, three hours a day. After recording, the rats were anesthetized and euthanized through cervical dislocation and their brains were excised. Biochemically, TNF-alpha, IL-6 and NO were studied in whole rat brains. RESULTS: In WAG/Rij rats, low-dose quercetin (25 mg/kg) reduced the number and duration of spike-wave discharges (SWDs) compared to the control group. However, 50 and 100 mg/kg quercetin doses increased SWDs. Duration of SWDs was prolonged only with 100 mg/kg dose. None of the quercetin doses had any effect on average amplitude of SWDs. In addition, it was observed in biochemical analyses that 25 mg/kg quercetin reduced TNF-alpha, IL-6 and NO levels compared to the control group. While TNF-alpha and IL-6 levels in rat brains were not affected by 50 or 100 mg/kg doses, both doses were found to increase NO levels in rat brains. CONCLUSION: Based on the results of the present study, 25 mg/kg low-dose quercetin may have reduced absence seizures by reducing proinflammatory cytokines and NO, but high-dose quercetin may have increased absence seizures through increasing the NO level. This contrasting effect of quercetin on absence seizures needs to be investigated by advanced mechanisms.

Electrophysiological, histopathological, and biochemical evaluation of the protective effect of probiotic supplementation against pentylenetetrazole-induced seizures in rats.

BACKGROUND AND PURPOSE: Research on the relationship between the gut microbiome and epilepsy is accumulating. The present study was conducted to evaluate the effect of probiotic supplementation on pentylenetetrazole (PTZ)-induced seizures in rats. METHODS: Twenty-one adult male Wistar albino rats were included. The animals were divided into three groups of seven rats. Group 1 was a control group, whereas Group 2 rats received PTZ treatment and Group 3 rats had PTZ+PB (probiotic) treatment. For 6 weeks, Groups 1 and 2 were given saline (1 ml), whereas Group 3 had probiotic supplement. In the 5th week, tripolar electrodes were attached to the rats. Electrophysiological, behavioral, biochemical, and immunohistochemical evaluations were performed in the 6 weeks after the treatment. RESULTS: PB treatment significantly reduced seizures. In the PTZ group, expression levels of brain-derived neurotrophic factor, nerve growth factor (NGF), and Sox2 (SRY sex-determining region Y-box 2) in rat brains decreased significantly compared to the control group, whereas the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total oxidant status (TOS), and nitric oxide (NO) levels increased. In the PTZ+PB group, NGF expression increased significantly compared to the PTZ group, whereas TNF-α, IL-6, TOS, and NO levels decreased. In histopathological examination, an abundance of necrotic neurons was notable in the PTZ group, which was less in the PTZ+PB group. In addition, body weight of the group supplemented with probiotics decreased after the treatment. CONCLUSIONS: Our results suggest that probiotic supplementation may alleviate seizure severity and exert neuroprotective effects by reducing neuroinflammation and oxidative stress and altering the expression of neurotrophins in epileptogenic brains.

The effect of Madopar on absence­like seizures in WAG/Rij rats.

The aim of this study was to investigate the effect of Madopar on the absence seizures and the anxiety­like behavior (assessed using the open field test) in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Twenty­eight male WAG/Rij rats were randomly divided into four groups: group I: control; group II: Madopar 5 mg/kg; group III: Madopar 50 mg/kg; group IV: Madopar 100 mg/kg. A tripolar electrode was attached to all WAG/Rij rats. Electrocorticography (ECoG) recordings were made before and after Madopar (5, 50, and 100 mg/kg) injection for three hours. Anxiety­related behavior was studied using the open field test for 5 min after the ECoG recordings. Madopar significantly reduced the number and duration of spike­wave discharges (SWDs) when compared to the control group. The highest dose of Madopar (100 mg/kg) significantly reduced the duration of SWDs when compared to Madopar (5 mg/kg). All Madopar doses did not alter the duration of grooming, but the highest doses of Madopar significantly increased the number of squares crossed in the open field test when compared to the control and Madopar (5 mg/kg) groups. These results revealed that Madopar reduced the absence­like seizures and the anxiety­related behavior in WAG/Rij rats. This may emphasize the therapeutic properties of the Madopar/L­dopa in absence epilepsy.

Probiotic supplementation alleviates absence seizures and anxiety- and depression-like behavior in WAG/Rij rat by increasing neurotrophic factors and decreasing proinflammatory cytokines.

AIM: Epilepsy is one of the most common chronic brain disorders that affect millions of people worldwide. In the present study, we investigated the effects of probiotic supplementation on absence epilepsy and anxiety-and depression-like behavior in WAG/Rij rats. MATERIAL AND METHOD: Fourteen male WAG/Rij rats (absence-epileptic) and seven male Wistar rats (nonepileptic) were used. The effects of probiotic VSL#3 (12.86 bn living bacteria/kg/day for 30 day/gavage) on absence seizures, and related psychiatric comorbidities were evaluated in WAG/Rij rats. Anxiety-like behavior was evaluated by the open-field test and depression-like behavior by the forced swimming test. In addition, the brain tissues of rats were evaluated histopathologically for nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], SRY sex-determining region Y-box 2 [SOX2] and biochemically for nitric oxide [NO], tumor necrosis factor-alpha [TNF-α] ,and Interleukin-6 [IL-6]. RESULTS: Compared to Wistar rats, WAG/Rij rats exhibited anxiety- and depression-like behavior, and had lower BDNF, NGF and SOX2 immunoreactivity, and higher TNF-α, IL-6 levels in brain tissue. VSL#3 supplementation reduced the duration and number of spike-wave discharges (SWDs) and exhibited anxiolytic or anti-depressive effect. VSL#3 supplement also increased the NGF immunoreactivity while decreasing IL-6, TNF-α and NO levels in WAG/Rij rat brain. CONCLUSION: The findings of the present study showed that neurotrophins, SOX2 deficiency, and pro-inflammatory cytokines may play a role in the pathogenesis of absence epilepsy. Our data support the hypothesis that the probiotics have anti-inflammatory effect. The present study is the first to show the positive effects of probiotic bacteria on absence seizures and anxiety- and depression-like behavior.

Vitamin D can reduce severity in COVID-19 through regulation of PD-L1.

COVID-19 is a highly contagious viral infection that has killed millions of people around the world. The most important diagnostic feature of COVID-19 is lymphocyte depletion, particularly the depletion of T cells. In COVID-19 infections, there is a link between destruction of T cells and increased expression of inhibitory immune checkpoint molecules (PD-1/PD-L1) on T cell surfaces. It was shown that PD-1/PD-L1 levels increase in severely COVID-19 infected individuals. Higher proinflammatory cytokine levels cause increased PD-1/PD-L1 expression. In severe COVID-19, higher proinflammatory cytokine levels may increase PD-1/PD-L1. Vitamin-D is an important immune regulator. It is known that the numbers of CD4+ and CD8+ T lymphocytes decrease in vitamin D deficiency while vitamin D supplementation increases CD + 4 lymphocytes. Vitamin D can increase regulatory T cell (Treg) activity. Vitamin D also has a diminishing effect on proinflammatory cytokines. In severe COVID-19 cases, vitamin D supplementation may inhibit the increase of PD-L1 expression through reducing proinflammatory cytokine levels. Thus, vitamin D supplementation could eliminate the suppressive effect of PD-L1 on CD4+ and CD8+ T cells, preventing lymphopenia and reducing disease severity and mortality in patients infected with COVID-19. Besides, vitamin D supplementation can reduce inflammation by increasing Treg activity. The aim of this letter is to discuss the functions of inhibitory immune checkpoint molecules and their effects on dysfunction and depletion of T-cells as well as to explain the possible modulatory effect of vitamin D on these checkpoints and T cells.

The Beneficial Effect of Probiotics Supplementation on Penicillin-Induced Focal Seizure in Rats.

The focal epilepsy is a chronic neurological brain disorder which affects millions of people in the world. There is emerging evidence that changes in the gut microbiota may have effects on epileptic seizures. In the present study, we examined the effect of probiotics on penicillin-induced focal seizure model in rats. Male Wistar Albino rats (n: 21) were randomly divided into three groups: control (no medication), penicillin and penicillin + probiotic. Probiotic VSL#3 (12.86 bn living bacteria/kg/day) was given by gavage for 30 days. The seizures were induced by intracortical injection of penicillin G (500 IU) into the cortex. An ECoG recordings were made for 180 min after penicillin G application. The spike frequency and the amplitude were used to assess the severity of seizures. Tumor necrosis factor (TNF-α), nitric oxide (NO) and interleukin (IL-6) levels in the brain were studied biochemically. Our results indicated that probiotic supplementation improved focal seizures through increasing the latency (p < 0.001) and decreasing the spike frequency (p < 0.01) compared to the penicillin group. Penicillin-induced seizure in rats significantly enhanced TNF-α (p < 0.01), NO (p < 0.01) and IL-6 (p < 0.05) compared to the control. Probiotic supplementation significantly decreased IL-6 (p < 0.05), TNF-α (p < 0.01) and NO (p < 0.001) compared to the penicillin group. When the body weights were compared before and after the experiment, there was no difference between the control and penicillin groups, but it was observed that the body weight decreased after probiotic supplementation in the penicillin + probiotic group. Probiotic supplementation may have anti-seizure effect by reducing proinflammatory cytokine and NO levels in epileptic rat brain.

Electrocorticographic and electrocardiographic evaluation of lacosamide in a penicillin-induced status epilepticus model.

AIM: The effect of lacosamide, a new antiseizure medication, was investigated electrophysiologically and biochemically in the penicillin-induced status epilepticus model. METHOD: The study included seven groups of rats (control, penicillin and 1, 5, 10, 25 and 50 mg/kg lacosamide). The rats were anesthetized using urethane (1.25 mg/kg/i.p.). ECG recordings were taken for one minute before and during status epilepticus in all groups. Lacosamide was administered intraperitoneally 30 min after intracortical microinjection of penicillin (500-IU/2.5/µl) and ECoG recording was taken for 180 min. The brain tissue was evaluated by ELISA method. RESULTS: Lacosamide (1, 5, 10 and 25 mg/kg) decreased spike frequency significantly, while 50 mg/kg lacosamide dose resulted in an increase in spike frequency. ST segment elevation and heart rate were higher in the penicillin group. Lacosamide doses of 1, 5, 10 and 25 mg/kg decreased ST-segment elevation to the level of the control group, but 50 mg/kg lacosamide increased ST-segment elevation, QT and PR-interval. TOS and TNF-alpha levels increased in the penicillin group compared to control group, while 10 mg/kg lacosamide dose limited this increase. 50 mg/kg lacosamide administration was found to decrease TAS level compared to control group. CONCLUSION: Our findings indicated associations of the decrease in spike frequency with the reduction of oxidative stress and inflammation in rats treated with 10 mg/kg lacosamide. High doses of lacosamide for acute treatment may cause cardiac changes in ECG.

Acute treatment with dexketoprofen reduces penicillin induced epileptiform activity in wistar albino rats (dexketoprofen in penicillin induced seizure model).

AIM: Dexketoprofen trometamol is one of the most commonly used anti-inflammatory analgesic agents for pain control. This study aims to investigate the effect of dexketoprofen on penicillin-induced epileptiform activity in rats. METHOD: In this study, 28 male Wistar rats weighing 220-240 g were used. Tripolar electrodes were implanted under urethane anesthesia. Epileptiform activity was induced by micro-injection of 500 units (IU) penicillin into the rats' left somatomotor cortex. Dexketoprofen (5, 25, and 50 mg/kg) was administrated intraperitoneally after 30 min of penicillin injection. Epileptiform activity was evaluated by electrocorticography (ECoG). RESULTS: The low dose of dexketoprofen administration (5 mg/kg) reduced the mean spike frequency of epileptiform activity 60 min after its injection. However, 25 and 50 mg/kg dexketoprofen significantly reduced the mean spike frequency 30 min after the dexketoprofen injection compared to the control group (p < 0.05). The amplitudes of epileptiform discharges in all groups were unaffected (p > 0.05). CONCLUSION: This study revealed that dexketoprofen had a significant anti-seizure effect when applied at 5 mg/kg, 25 mg/kg, and 50 mg/kg (especially at 25 and 50 mg/kg), in the penicillin-induced seizure model. The obtained data revealed that dexketoprofen might play an essential role against epileptic seizures.

Vitamin D may prevent COVID-19 induced pregnancy complication.

SARS-CoV-2 enters target cells via the ACE2 receptor and downregulates it. ACE2 exhibits high catalytic activity to produce Angiotensin 1-7 (Ang-1-7), which has a vasodilator effect and also inactivates the vasoconstrictor Angiotensin II. In normal pregnancy ACE2 expression is raising in the uterus and placenta. Ang-1-7 levels in plasma are significantly higher in third-trimester pregnant women when compared to non-pregnant women. This may be contributing to systemic vasodilation and reduced blood pressure and modulating hemodynamics during pregnancy. Interestingly, Ang-1-7 plasma levels are lower in pregnancies complicated by pre-eclampsia than normal pregnancies. COVID-19 infection increased the inflammatory cytokines and reduced ACE2 level. This may lead to pre-eclampsia or hypertensive pregnancies, then increasing the perinatal and maternal mortality and morbidity. Vitamin D increased ACE2 expression and Ang-1-7 plasma levels and also decreased Ang II level in plasma. Moreover, Vitamin D reduced the inflammatory cytokine storm. So, Vitamin D supplementation can prevent the risk of preeclampsia or hypertension in pregnant women with COVID-19.

Exendin-4 increases absence-like seizures and anxiety-depression-like behaviors in WAG/Rij rats.

AIM: Epilepsy is a neurological condition affecting millions of people worldwide. Glucagon-like peptide-1 (GLP-1) is a gut hormone, and its neuroprotective effect was investigated in previous studies. In this study, the effects of exendin-4, a GLP-1 receptor agonist, were studied in genetic absence epileptic Wistar Albino Glaxo/Rijswijk rats (WAG/Rij). WAG/Rij rat is a genetic model of the absence epilepsy and depression-like comorbidity. METHOD: We examined the effects of exendin-4 (10, 50 and 100 µg/kg) on the absence seizures (Electrocorticography [ECoG] recordings), anxiety level (open-field test [OF]), and depression-like levels (forced swimming test [FST]) in the WAG/Rij rats. Basal ECoG recording was performed for all rats. Then, exendin-4 (10, 50 or 100 µg/kg) was administered intraperitoneally and ECoG recording was made for 180 min. After ECoG recording, forced swimming test and open-field test were applied. RESULTS: Administration of 10, 50, or 100 µg/kg exendin-4 increased the duration and number of spike-wave discharges (SWDs) considerably without changing the amplitude. The 100 µg/kg dose of exendin-4 was the most effective in increasing the total duration of SWDs. Additionally, all exendin-4 doses increased anxiety level in OF and depression-like level in FST. CONCLUSION: Our results showed that exendin-4 increased SWD incidence and anxiety- and depression-like behaviors in the WAG/Rij rats. Besides, it was also found that high doses caused the most proabsence effect.

The effect of dexketoprofen trometamol on WAG/Rij rats with absence epilepsy (dexketoprofen in absence epilepsy).

AIM: Epilepsy is one of the most common neurological diseases. Dexketoprofen (DEX) is a nonselective nonsteroidal anti-inflammatory drug that is used as an analgesic. The present study aimed to assess the efficiency of DEX on WAG/Rij rats by electrophysiologically and behaviorally. MATERIAL AND METHODS: Twenty-eight male WAG/Rij rats were used. The effects of acute treatment with DEX (5, 25, and 50 mg/kg, i.p) on absence-like seizures, and related psychiatric comorbidity were assessed. The ECoG recording was taken for 180 min before and after drug injection. After drug injection and EcoG recording, anxiety-depression-like behavior was tested with the open field test for 5 min. RESULTS: The 5 mg/kg DEX significantly reduced the number and duration of SWDs percentage (p < 0.05) between 120 and 180 min, but 25 and 50 mg/kg DEX significantly increased the number and duration of SWDs percentage between 0 and 30 min (p < 0.05), and after 30 min the increase stopped (p > 0.05). And also, the 5 mg/kg DEX decreased the number and duration of SWDs percentage (p < 0.05) for 180 min (p < 0.05), but 25 and 50 mg/kg DEX administration did not alter (p > 0.05). The 5, 25, and 50 mg/kg doses of DEX significantly increased the duration of grooming (p < 0.05) but did not change the number of squares crossed (p > 0.05). CONCLUSION: Low dose DEX reduced absence-like seizures, but care should be taken when using high doses in absence epilepsy. Also, it may be beneficial for painful diseases accompanied by anxiety-depression.

Chronic effects of different quercetin doses in penicillin-induced focal seizure model.

AIM: The aim of the present study was to examine the effects of different quercetin pretreatment doses on focal epileptiform activity induced by penicillin in adult male rat cortex. METHOD: Twenty-eight male Wistar rats weighing 200-235 g were randomly divided into four groups: control (only penicillin-injected group) and penicillin + 25, 50 or 100 mg/kg quercetin doses. All quercetin-treated rats had a daily single dose of 25, 50 or 100 mg/kg intraperitoneally administered quercetin for 21 days, and the last dose was given 30 min before the penicillin injection. Epileptiform activity was induced by a single intracortical (i.c.) microinjection of penicillin (500 units/2.5 µl) into left motor cortex. After penicillin injection ECoG was recorded for the following 180 min. RESULTS: Quercetin pretreatments of 25, 50 and 100 mg/kg significantly increased the duration of latency (initial spike activity) and decreased spike frequency of the epileptiform activity compared to the control group (p < 0.05). Duration of latency was significantly longer in 25 mg/kg quercetin pretreatment group compared to 100 mg/kg group (p < 0.05). Spike amplitude of epileptiform activity was not different in the study groups (p > 0.05). CONCLUSION: Quercetin had an anticonvulsant activity in penicillin-induced focal seizure model in the present study. In addition, lower quercetin doses had highest anticonvulsant effect in this model.

Vortioxetine increases absence-like seizures in WAG/Rij rats but decreases penicillin- and pentylenetetrazole-induced seizures in Wistar rats.

AIM: Depression is the major psychiatric disorder in patients with epilepsy. Vortioxetine is a novel antidepressant drug for the treatment of major depressive disorders. In the present study, effects of vortioxetine were evaluated in different experimental epilepsy models of rats. MATERIALS AND METHODS: Fifty-six adult male Wistar rats and 28 WAG/Rij rats were divided into 12 groups of 7 rats each. Experiments were conducted with penicillin (500 IU, i.c.) and pentylenetetrazole models (50 mg/kg, intraperitoneally (i.p.)) in Wistar rats and genetic absence epileptic WAG/Rij rats. The vortioxetine (1, 5, or 10 mg/kg, i.p.) was evaluated in these three models. All groups were compared with their control groups. RESULTS: In the penicillin-induced seizure model, 1, 5, or 10 mg/kg vortioxetine administration significantly decreased mean spike frequency. In the pentylenetetrazole-induced seizure model, 1, 5, or 10 mg/kg vortioxetine demonstrated a significant dose-dependent decrease in mean spike frequency, an increase in the latency to minor and major seizures, and a decrease in total duration of major seizure and convulsion stage. In genetic absence epileptic WAG/Rij rats, 1 mg/kg vortioxetine caused no significant alteration in the number and duration of SWDs compared to the controls, while 5 and 10 mg/kg doses of vortioxetine increased the number and duration of SWDs. Amplitude of the epileptiform activity did not change in any of the experimental epilepsy models. CONCLUSION: The results of this study suggested that vortioxetine has anticonvulsant activity in penicillin- and pentylenetetrazole-induced seizure models. However, it exhibited proconvulsant activity in the absence epileptic WAG/Rij rats.

Anticonvulsive effects of edaravone on penicillin-induced focal onset seizure model in the conscious rats.

Edaravone is a potent antioxidant and anti-inflammatory agent that is used in the clinic. The aim of the present study was to evaluate the chronic treatment effect of edaravone on penicillin-induced epileptiform activity. Twenty-eight Wistar rats were randomly divided into a total of four groups as penicillin control and edaravone pretreatment groups (1, 10, and 30mg/kg). Firstly, permanent electrodes for electrocorticography (ECoG) recording and canula for penicillin injection were placed as stereotactic under anesthesia. At the end of the recovery period, edaravone pretreatment groups received different doses of edaravone by intraperitoneal injection for 14 days and before 30-min penicillin microinjection. Epileptiform activity was induced by injecting 500 IU penicillin through the intracortical cannula. The effects of edaravone pretreatment on epileptiform activity were evaluated by using both electrophysiological and behavioral parameters. Edaravone pretreatment suppressed epileptiform activity by reducing the mean spike frequency and the behavior scores in ECoG recording. The results of the present study indicated that the use of chronic edaravone had an anticonvulsant effect on penicillin-induced focal onset epileptic activity. Edaravone had an anticonvulsant effect even at low doses.

Vitamin D deficiency is associated with COVID-19 positivity and severity of the disease.

The present study examined the relationship between polymerase chain reaction (PCR) test positivity and clinical outcomes of vitamin D levels measured within the 6 months before the PCR test in coronavirus disease 2019 (COVID-19)-positive patients. In this retrospective cohort study, COVID-19 (227) and non-COVID-19 patients (260) were divided into four groups according to their vitamin D levels: Group I (0-10 ng/ml), Group II (10-20 ng/ml), Group III (20-30 ng/ml), and Group IV (vitamin D > 30 ng/ml). Laboratory test results and the radiological findings were evaluated. In addition, for comparative purposes, medical records of 1200 patients who had a hospital visit in the November 1, 2019-November 1, 2020 period for complaints due to reasons not related to COVID-19 were investigated for the availability of vitamin D measurements. This search yielded 260 patients with tested vitamin D levels. Vitamin D levels were below 30 ng/ml in 94.27% of 227 COVID-19-positive patients (average age, 46.32 ± 1.24 years [range, 20-80 years] and 56.54% women) while 93.07% of 260 non-COVID-19 patients (average age, 44.63 ± 1.30 years [range, 18-75 years] and 59.50% women) had vitamin D levels below 30 ng/ml. Nevertheless, very severe vitamin D deficiency (<10 ng/ml) was considerably more common in COVID-19 patients (44%) (average age, 44.15 ± 1.89 years [range, 23-80 years] and 57.57% women) than in non-COVID-19 ones (31%) (average age, 46.50 ± 2.21 years [range, 20-75 years] and 62.5% women). Among COVID-19-positive patients, the group with vitamin D levels of >30 ng/ml had significantly lower D-dimer and C-reactive protein (CRP) levels, number levels, number of affected lung segments and shorter hospital stays. No difference was found among the groups in terms of age and gender distribution. Elevated vitamin D levels could decrease COVID-19 PCR positivity, D-dime and CRP levels and the number of affected lung segments in COVID-19-positive patients, thereby shortening the duration of hospital stays and alleviating the intensity of COVID-19.

Evaluation of the protective effect of paricalcitol and vitamin D3 at doxorubicin nephrotoxicity in rats with 99mTechnetium-dimercaptosuccinic acid renal scintigraphy and biochemical methods.

AIM: The present study aimed to examine the effect of paricalcitol (PRC) and vitamin D3 (vit D3) on doxorubicin (DOX)-induced nephrotoxicity in rats. MATERIALS AND METHODS: Forty-two Wistar rats were randomly categorized into six groups: control; 2) PRC(0.5 µg/kg) and 3) vit D3(5.000 IU/kg) administered for 14 days; 4) DOX, 18 mg/kg administered on the 12th, 13th and 14th days of the study; 5) PRC (0.5 µg/kg, +DOX(18 mg/kg); vit D3(5.000 IU)+DOX(18 mg/kg). On the 15th day of the experiment, 99mTc-DMSA uptake level and biochemical parameter in serum and tissue were assay. RESULTS: Activities of 99mTechnetium-Dimercaptosuccinic Acid (99mTc-DMSA) were lower in groups receiving DOX and/or PRC+DOX, vit D3+DOX than in control groups. The 99mTc-DMSA level in the group PRC+DOX and vit D3+DOX were importantly higher than DOX group. DOX caused an important increase in blood urea nitrogen (BUN), creatinine, Tumor Necrosis Factor-α(TNF- α), interleukin-6(IL-6) and nitric oxide(NO) levels compared to control groups. However, PRC and vit D3 pretreatments lowered them. Uptake of 99mTc-DMSA level was higher in groups PRC+DOX than in vit D3+DOX group. Administration of PRC and vit D3 alone did not change alterations all of parameters. CONCLUSION: The results indicated that PRC administration protects kidney in DOX-induced nephrotoxic rats. In addition, PRC has a stronger nephroprotective effect than vit D3.

The Role of NMDA Receptors in the Effect of Purinergic P2X7 Receptor on Spontaneous Seizure Activity in WAG/Rij Rats With Genetic Absence Epilepsy.

P2X7 receptors (P2X7Rs) are ATP sensitive cation channels and have been shown to be effective in various epilepsy models. Absence epilepsy is a type of idiopathic, generalized, non-convulsive epilepsy. Limited data exist on the role of P2X7Rs and no data has been reported regarding the interaction between P2X7Rs and glutamate receptor NMDA in absence epilepsy. Thus, this study was designed to investigate the role of P2X7 and NMDA receptors and their possible interaction in WAG/Rij rats with absence epilepsy. Permanent cannula and electrodes were placed on the skulls of the animals. After the healing period of the electrode and cannula implantation, ECoG recordings were obtained during 180 min before and after drug injections. P2X7R agonist BzATP, at doses of 50 µg and 100 µg (intracerebroventricular; i.c.v.) and antagonist A-438079, at doses of 20 µg and 40 µg (i.c.v.) were administered alone or prior to memantine (5 mg/kg, intraperitoneal; i.p.) injection. The total number (in every 20 min), the mean duration, and the amplitude of spike-wave discharges (SWDs) were calculated and compared. Rats were decapitated and the right and left hemisphere, cerebellum, and brainstem were separated for the measurements of the advanced oxidation protein product (AOPP), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), glutathione peroxide (GPx), and glutathione reductase (GR). BzATP and A-438079 did not alter measured SWDs parameters, whereas memantine reduced them, which is considered anticonvulsant. BzATP did not alter the anticonvulsant effect of memantine, while A-438079 decreased the effect of memantine. Administration of BzATP increased the levels of SOD and GR in cerebrum hemispheres. A-438079 did not alter any of the biochemical parameters. Memantine reduced the levels of MDA, GSH, and GR while increased the level of CAT in the cerebrum. Administration of BzATP before memantine abolished the effect of memantine on MDA levels. The evidence from this study suggests that P2X7Rs does not directly play a role in the formation of absence seizures. P2X7Rs agonist, reduced the antioxidant activity of memantine whereas agonist of P2X7Rs reduced the anticonvulsant action of memantine, suggesting a partial interaction between P2X7 and NMDA receptors in absence epilepsy model.

Vitamin D can prevent COVID-19 infection-induced multiple organ damage.

Vitamin D is an immunomodulator hormone with an anti-inflammatory and antimicrobial effect with a high safety profile. A lot of COVID-19 infected patients develop acute respiratory distress syndrome (ARDS), which may lead to multiple organ damage. These symptoms are associated with a cytokine storm syndrome. The aim of this letter is to note the 5 crucial points that vitamin D could have protective and therapeutic effects against COVID-19. For that reason, COVID-19 infection-induced multiple organ damage might be prevented by vitamin D.