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Article ; Online: Vitamin D can reduce severity in COVID-19 through regulation of PD-L1.

Aygun, Hatice

Naunyn-Schmiedeberg's archives of pharmacology

2022 Volume 395, Issue 4, Page(s) 487–494

Abstract: 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 ...

Abstract	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
MeSH term(s)	Animals ; B7-H1 Antigen/drug effects ; B7-H1 Antigen/metabolism ; COVID-19/drug therapy ; COVID-19/immunology ; Cytokines/metabolism ; Humans ; Vitamin D/therapeutic use
Chemical Substances	B7-H1 Antigen ; CD274 protein, human ; Cytokines ; Vitamin D (1406-16-2)
Language	English
Publishing date	2022-01-31
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-022-02210-w
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Article ; Online: Exendin-4 increases absence-like seizures and anxiety-depression-like behaviors in WAG/Rij rats.

Aygun, Hatice

Epilepsy & behavior : E&B

2021 Volume 123, Page(s) 108246

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Anxiety/drug therapy ; Depression/drug therapy ; Disease Models, Animal ; Electroencephalography ; Epilepsy, Absence/drug therapy ; Epilepsy, Absence/genetics ; Exenatide/therapeutic use ; Rats ; Rats, Wistar ; Seizures/drug therapy
Chemical Substances	Exenatide (9P1872D4OL)
Language	English
Publishing date	2021-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010587-3
ISSN	1525-5069 ; 1525-5050
ISSN (online)	1525-5069
ISSN	1525-5050
DOI	10.1016/j.yebeh.2021.108246
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Article ; Online: Vitamin D can prevent COVID-19 infection-induced multiple organ damage.

Aygun, Hatice

Naunyn-Schmiedeberg's archives of pharmacology

2020 Volume 393, Issue 7, Page(s) 1157–1160

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Anti-Inflammatory Agents/administration & dosage ; Anti-Inflammatory Agents/pharmacology ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Coronavirus Infections/virology ; Cytokine Release Syndrome/prevention & control ; Cytokine Release Syndrome/virology ; Humans ; Multiple Organ Failure/prevention & control ; Multiple Organ Failure/virology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/virology ; Respiratory Distress Syndrome/prevention & control ; Respiratory Distress Syndrome/virology ; Vitamin D/administration & dosage ; Vitamin D/pharmacology ; COVID-19 Drug Treatment
Chemical Substances	Anti-Inflammatory Agents ; Vitamin D (1406-16-2)
Keywords	covid19
Language	English
Publishing date	2020-05-25
Publishing country	Germany
Document type	Letter
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-020-01911-4
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Article ; Online: The effect of duloxetine on ECoG activity of absence-epilepsy model in WAG/Rij rats

Hatice Aygün

Journal of Contemporary Medicine, Vol 9, Iss 3, Pp 235-

2019 Volume 239

Abstract: Aim: Many epidemiological studies have found a high incidence of depression and anxiety in people with epilepsy. Duloxetine is a selective inhibitor of serotonin and norepinephrine reuptake (SNRI) and commonly prescribed in a patient with major ... ...

Abstract	Aim: Many epidemiological studies have found a high incidence of depression and anxiety in people with epilepsy. Duloxetine is a selective inhibitor of serotonin and norepinephrine reuptake (SNRI) and commonly prescribed in a patient with major depressive disorder. The aim of this study was to investigate the effect of duloxetine on the WAG/Rij rat in an experimental rat model of absence-epilepsy. Methods: WAG/Rij rats were randomly assigned into 5 groups with 7 animals in each group. Tripolar electrodes were placed on the skull to perform electrocorticography (ECoG) evaluation. Then, following the recovery period, ECoGs were recorded at 09:00 am for 3 hours every day. Subsequently, duloxetine (1, 5, 10 and 30 mg/kg) was injected intraperitoneally (i.p). After the treatment program, ECoG recordings were taken for 3 hours. And then all animal anxiety-like behavior by using the behavioral test, open field test (OFT) was performed after duloxetine (1,5,10 and 30 mg/kg) treatment. The total number and the total duration of the spike-wave discharges (SWDs) were calculated offline. The number of squares crossed (locomotor activity) and the duration of grooming episodes were analyzed in OFT. Results: The doses of duloxetine (1 mg/kg) did not alter ECoG and OFT parameters. The 5, 10 and 30 mg/kg doses of duloxetine decreased the total number and the total duration of SWDs, (p<0.05) and increased the number of squares crossed when compared to with control group (p <0.05) without changing duration of grooming episodes (p> 0.05). Intraperitoneal administering of 1 mg/kg duloxetine did not show any statistically significant change in regard to the number and duration of SWDs. Conclusions: In the present study, duloxetine reduce dose-dependent absences-like seizures and anxiety-like behavior.
Keywords	duloksetin ; absans epilepsi ; waj/rij sıçan ; ecog ; açık alan testi ; duloxetine ; absence epilepsy ; waj/rij rat ; open field test ; Medicine ; R
Subject code	630
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Rabia Yılmaz
Document type	Article ; Online
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Article: Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats.

Koroglu, Reyhan / Koroglu, Mustafa / Aygun, Hatice

Bratislavske lekarske listy

2024 Volume 125, Issue 5, Page(s) 281–288

Abstract: 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 ( ...

Abstract	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.
MeSH term(s)	Rats ; Male ; Animals ; Cardiotoxicity/drug therapy ; Cardiotoxicity/prevention & control ; Receptors, Calcitriol/therapeutic use ; Rats, Wistar ; Cholecalciferol/pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; Interleukin-6 ; Electrocardiography ; Doxorubicin/toxicity ; Antioxidants/pharmacology ; Radionuclide Imaging ; Oxidative Stress ; Ergocalciferols
Chemical Substances	paricalcitol (6702D36OG5) ; Receptors, Calcitriol ; Cholecalciferol (1C6V77QF41) ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Doxorubicin (80168379AG) ; Antioxidants ; Ergocalciferols
Language	English
Publishing date	2024-01-12
Publishing country	Slovakia
Document type	Journal Article
ZDB-ID	127421-1
ISSN	0006-9248
ISSN	0006-9248
DOI	10.4149/BLL_2024_42
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Article ; Online: The effect of fluoxetine on penicillin-induced epileptiform activity.

Aygun, Hatice

Epilepsy & behavior : E&B

2019 Volume 95, Page(s) 79–86

Abstract: Aim: Depression is the most frequent psychiatric comorbidity in patients with epilepsy. Fluoxetine is the most widely used selective serotonin reuptake inhibitor (SSRI) in depression. The aim of the present study was to evaluate the dose-dependent ... ...

Abstract	Aim: Depression is the most frequent psychiatric comorbidity in patients with epilepsy. Fluoxetine is the most widely used selective serotonin reuptake inhibitor (SSRI) in depression. The aim of the present study was to evaluate the dose-dependent effect of fluoxetine on penicillin-induced seizure by electrocorticogram (ECoG), a model for simple partial epilepsy. Method: The epileptiform activity was induced by intracortical (i.c.) microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, 5, 10, or 20 mg/kg doses of fluoxetine were administered intraperitoneally (i.p.). An ECoG recording was performed for 180 min using the data acquisition system. The frequency and the amplitude of the epileptiform activity were analyzed. Results: Penicillin induced bilateral spikes and spike-wave complexes within 2-5 min. The 5 and 10 mg/kg doses of fluoxetine significantly reduced the frequency (58%, p < 0.05 and 69%, p < 0.01, 40 and 50 min after fluoxetine injection, respectively) and amplitude (60%, p < 0.01 and 73%, p < 0.05, 40 and 120 min after fluoxetine injection, respectively) of epileptiform activity compared with penicillin-induced seizure group (control). Five-milligram fluoxetine (i.p.) was the most effective dose to decrease frequency and amplitude on penicillin-induced epileptiform activity. However, a higher fluoxetine dose (20 mg/kg) significantly increased frequency (147%, p < 0.01) and amplitude (123%, p < 0.05) of epileptiform activity 40 and 120 min after fluoxetine administration compared with control group. Also, bursts of population spikes were seen in 20 mg/kg fluoxetine doses. Conclusion: Results of the present study indicate that low and moderate fluoxetine doses have an anticonvulsant effect while high doses have proconvulsant effect on penicillin-induced epileptic activity.
MeSH term(s)	Animals ; Anti-Bacterial Agents/pharmacology ; Anticonvulsants/administration & dosage ; Anticonvulsants/pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Electrocorticography ; Electroencephalography/drug effects ; Epilepsies, Partial/chemically induced ; Epilepsies, Partial/drug therapy ; Fluoxetine/administration & dosage ; Fluoxetine/pharmacology ; Male ; Penicillins/pharmacology ; Rats ; Rats, Wistar ; Serotonin Uptake Inhibitors/administration & dosage ; Serotonin Uptake Inhibitors/pharmacology
Chemical Substances	Anti-Bacterial Agents ; Anticonvulsants ; Penicillins ; Serotonin Uptake Inhibitors ; Fluoxetine (01K63SUP8D)
Language	English
Publishing date	2019-04-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010587-3
ISSN	1525-5069 ; 1525-5050
ISSN (online)	1525-5069
ISSN	1525-5050
DOI	10.1016/j.yebeh.2019.03.050
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Article ; Online: Trazodone increases seizures in a genetic WAG/Rij rat model of absence epilepsy while decreasing them in penicillin-evoked focal seizure model.

Aygun, Hatice

Epilepsy & behavior : E&B

2019 Volume 103, Issue Pt A, Page(s) 106847

Abstract: Aim: Psychiatric disorders, especially depression and anxiety, are among the most disabling comorbidities in patients with epilepsy, and they are difficult to treat because many antidepressants cause proconvulsive effects. Thus, it is important to ... ...

Abstract	Aim: Psychiatric disorders, especially depression and anxiety, are among the most disabling comorbidities in patients with epilepsy, and they are difficult to treat because many antidepressants cause proconvulsive effects. Thus, it is important to identify the seizure risks associated with antidepressants. Trazodone is one of the most frequently prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs for the treatment of depression and anxiety. The aim of the present study was to evaluate the effects of trazodone on epileptiform activity in a penicillin-evoked focal seizure model in Wistar rats and in a genetic absence epilepsy model in Wistar Albino Glaxo/Rijswijk strain (WAG/Rij) rats. Methods: Trazodone at 5-, 10-, and 30-mg/kg doses was injected intraperitoneally in Wistar rats 30 min after penicillin injection, and spike frequency and amplitude of penicillin-induced epileptiform activity were evaluated. In a separate experimental model, the same trazodone doses were injected in WAG/Rij rats to elucidate their effects on number, duration, and amplitude of spike-and-wave discharges (SWDs) and on depression-anxiety like behavior. In both experimental groups, after trazodone injections recordings were made for 3 h. Depression-anxiety like behaviors in WAG/Rij rats were examined using forced swim test and open-field test. Results: Trazodone at 10- and 30-mg/kg doses significantly reduced the frequency of penicillin-induced epileptiform activity without changing the amplitude. Trazodone at a 5-mg/kg dose had no effect on either frequency or amplitude of epileptiform activity. Trazodone at all doses significantly increased number and duration of SWDs without changing the amplitude. In addition, all doses of trazodone decreased the number of squares crossed and duration of grooming in open-field test, and reduced swimming time activity and increased immobility time in forced swim test. Conclusion: Our results suggest that depending on the dose used, trazodone had an anticonvulsant effect or no effect on penicillin-evoked focal seizure model, but all trazodone doses resulted in proconvulsant and depression-anxiety like behavior in WAG/Rij rats, which represent a genetic absence model of epilepsy.
MeSH term(s)	Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Electroencephalography/methods ; Epilepsy, Absence/chemically induced ; Epilepsy, Absence/drug therapy ; Epilepsy, Absence/physiopathology ; Injections, Intraperitoneal ; Male ; Penicillins/toxicity ; Rats ; Rats, Inbred Strains ; Rats, Transgenic ; Rats, Wistar ; Seizures/chemically induced ; Seizures/drug therapy ; Seizures/physiopathology ; Serotonin Uptake Inhibitors/administration & dosage ; Serotonin Uptake Inhibitors/adverse effects ; Serotonin Uptake Inhibitors/therapeutic use ; Trazodone/administration & dosage ; Trazodone/adverse effects
Chemical Substances	Penicillins ; Serotonin Uptake Inhibitors ; Trazodone (YBK48BXK30)
Language	English
Publishing date	2019-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010587-3
ISSN	1525-5069 ; 1525-5050
ISSN (online)	1525-5069
ISSN	1525-5050
DOI	10.1016/j.yebeh.2019.106847
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Article ; Online: Vitamin D can prevent COVID-19 infection-induced multiple organ damage

Aygun, Hatice

Naunyn-Schmiedeberg's Archives of Pharmacology

2020 Volume 393, Issue 7, Page(s) 1157–1160

Keywords	Pharmacology ; General Medicine ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-020-01911-4
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Article ; Online: Electrocorticographic and electrocardiographic evaluation of lacosamide in a penicillin-induced status epilepticus model.

Sumbul, Orhan / Aygun, Hatice

Epilepsy research

2022 Volume 180, Page(s) 106866

Abstract: 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, ...

Abstract	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.
MeSH term(s)	Animals ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Electrocardiography ; Lacosamide/therapeutic use ; Penicillins/adverse effects ; Rats ; Status Epilepticus/chemically induced ; Status Epilepticus/drug therapy
Chemical Substances	Anticonvulsants ; Penicillins ; Lacosamide (563KS2PQY5)
Language	English
Publishing date	2022-01-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	632939-1
ISSN	1872-6844 ; 0920-1211
ISSN (online)	1872-6844
ISSN	0920-1211
DOI	10.1016/j.eplepsyres.2022.106866
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Article: Vitamin D can prevent COVID-19 infection-induced multiple organ damage

Aygun, Hatice

Naunyn Schmiedebergs Arch Pharmacol

Abstract	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.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #361504
Database	COVID19

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