scholarly journals Role of nicotine in depression through dopaminergic mechanism

2017 ◽  
Vol 6 (4) ◽  
pp. 864
Author(s):  
Rahul Raghunath Bhalsinge ◽  
Rajbhoj Satkar ◽  
Sayan Das ◽  
Shraddha Yadav ◽  
Shah A. S. ◽  
...  
Keyword(s):  
Single Dose ◽  
Antidepressant Drug ◽  
Treated Group ◽  
Dopamine Level ◽  
Dopaminergic Activity ◽  
Dopaminergic Mechanism ◽  
Relationship Of ◽  
Vehicle Treated Group ◽  
Antidepressant Action

Background: There are interesting reports in the literature indicating relationship of smoking /nicotine and depression. Smokers use nicotine to treat depression. The objectives of present study were to evaluate the role of nicotine in depression through Dopaminergic mechanism by using haloperidol induced catalepsy model in rats and to estimate Dopamine level in brain of depressed rats after nicotine and imipramine.Methods: Dopaminergic activity was evaluated in haloperidol induced catalepsy in rats. Levels of dopamine in normal as well as in depressed rats brain was estimated using fluorimetric method. The study treatment were administered as follows - Vehicle (s.c.), Imipramine (i.p.) - 7days, Nicotine (subcutaneous), Nicotine (inhalation) were administered in a dose of 1ml/kg,10mg/kg,0.4mg/kg,0.2mg/kg respectively.Results: In haloperidol induced catalepsy model, vehicle treated group showed cataleptic effect starting at 1 hour and lasting for 6 hours. Nicotine administered by subcutaneous route significantly reduced cataleptic score as compared to vehicle treated group till 6 hours. Nicotine administered by inhalation route reduced cataleptic score up to 6 hours compared with that of vehicle. Catalepsy score in nicotine (inhalation) group was significantly less as compared to nicotine (subcutaneous) at all time points period except 2 hours. Isolation induced hyperactivity model was used to induce depression in rats. Dopamine levels in rats after isolation were significantly less as compared to normal rats (before isolation). After isolation, dopamine levels in imipramine treated rats were significantly higher as compared to vehicle treated group. After isolation, dopamine levels were significantly high in both groups i.e., nicotine (subcutaneous) and nicotine (inhalation). Imipramine (7 days) and single dose of nicotine (inhalation) showed comparable results with normal dopamine level i.e. before isolation rats.Conclusions: Nicotine has increased dopaminergic activity as evident by reversal of haloperidol induced catalepsy. Dopamine level reduced in depressed rats. Dopamine brain levels were increased, when depressed rats were treated with Imipramine (i.p.), nicotine (s.c.), nicotine(inhaled). Single dose nicotine given by inhalation route has produced significant antidepressant action comparable to that of seven days’ treatment of standard antidepressant drug imipramine in rats. In rats, nicotine by both routes i.e subcutaneous and inhalational increased dopaminergic activity.

scholarly journals Effect of nicotine on serotonin (5-HT) levels in brain of depressed rats

2017 ◽  
Vol 6 (4) ◽  
pp. 938
Author(s):  
Rahul R. Bhalsinge ◽  
Anita A. Barde ◽  
Pratibha S. Worlikar ◽  
Manasi V. Limaye ◽  
Mrunal P. Dhole ◽  
...  
Keyword(s):  
Single Dose ◽  
Statistical Significance ◽  
Antidepressant Drug ◽  
Study Groups ◽  
Treated Group ◽  
Brain Serotonin ◽  
Background Reduction ◽  
Serotonergic Activity ◽  
Vehicle Treated Group ◽  
Antidepressant Action

Background: Reduction in brain serotonin (5-HT) levels contributes to depression. Nicotine may have antidepressant properties and smokers self-medicate underlying depression. Epidemiological findings suggest that smokers more often demonstrate depressive symptoms than non-smokers and depressed patients are less likely to cease smoking. Therefore, the study was planned to evaluate the effect of nicotine on serotonin levels in brain of depressed rats.Methods: Antidepressant action of study drugs was evaluated using isolation induced hyperactivity model in rats. Rats were divided into five groups with six rats in each group. Study groups: Vehicle in normal rats 1 ml/kg (subcutaneous); vehicle after isolation 1ml/kg (subcutaneous); imipramine 10 mg/kg (intraperitoneal) for 7 consecutive days; single dose of nicotine 0.4 mg/kg (subcutaneous); single dose of nicotine 0.2 mg/kg (inhalational). Brain serotonin assay was carried out. The statistical significance was determined by ANOVA followed by Tukey test (p<0.05).Results: Serotonin levels (55.93ng/g of brain tissue) in rats after isolation were significantly less than in normal rats (335.87ng/g) (p<0.001). In imipramine treated group, serotonin levels (301.4ng/g) after isolation were highly significant as compared to serotonin levels in vehicle treated group after isolation (p<0.001). Nicotine administered by subcutaneous and inhalational route showed significantly higher brain serotonin levels, i.e. 175ng/g and 254.62ng/g respectively as compared to vehicle treated rats after isolation (p<0.001).Conclusions: Single dose nicotine (inhalational) produced significant antidepressant action comparable to that of seven days’ treatment of standard antidepressant drug imipramine in rats. In rats, nicotine by both routes i.e. subcutaneous and inhalational increased serotonergic activity.

Abstract 450: The Role of CD38 as a Therapeutic Target for Protection Against Doxorubicin-induced Cardiotoxicity Through Nad+ Boosting

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Thais R Peclat ◽  
Guillermo Agorrody ◽  
Lilian S Gomez ◽  
Eduardo N Chini
Keyword(s):  
Single Dose ◽  
Therapeutic Target ◽  
Potential Role ◽  
Damage Mechanism ◽  
Treated Group ◽  
Wild Type ◽  
Chemotherapeutic Treatment ◽  
Positive Effect ◽  
Dose Injection

Background: Doxorubicin is a chemotherapy medication used to treat several types of cancer. Its major adverse effect is cardiotoxicity, which may limit its use. Doxorubicin-induced cardiotoxicity (DIC), once developed, carries a poor prognosis. Therefore strategies to prevent or treat DIC are of paramount importance but have not yet been fully developed. Being NAD + a critical nucleotide which is involved in oxy-reduction reactions and CD38 the main NAD + -consuming enzyme responsible for NAD levels regulation and homeostasis, we aim to investigate the link of CD38 and NAD + metabolism in DIC and its potential role as a therapeutic target. Methods: We compared Wild-type (WT) control mice with WT mice treated with a single dose injection of 15 mg/kg of doxorubicin who received vehicle or an antibody that blocksCD38 ecto-enzymatic activity. We also compared genetically CD38 catalytic inactive (CI) mice treated or not with the same single dose injection. Results: Doxorubicin caused a decrease in Ejection Fraction (EF) in WT mice. We also observed that CD38 CI mice treated with doxorubicin did not have changes in EF compared to their control. When compared to WT receiving just doxorubicin, WT mice treated also with the antibody had a trend to improve EF. As for exercise performance, our results show a decrease in exercise capacity induced by doxorubicin that was reversed in the antibody group and did not happen in the CD38 CI mice treated with doxorubicin. Doxorubicin caused a decrease in heart rate variability (HRV) which was improved in the antibody treated group. Moreover, our results show a survival rate that is similar to what has been previously shown, with 50% mortality associated with doxorubicin. Blockage of CD38 activity with antibody reduced mortality in this model to approximately 20%. Mechanistically, we did not observe decreases in NAD+ levels induced by Doxorubicin. However, boost of NAD induced by blocking CD38 was related to protection against DIC. Conclusion: Our results indicate that the damage mechanism of DIC may not be related directly with NAD decrease, but NAD boosting induced by CD38 blockage seems to have a positive effect in protection against cardiac dysfunction related to this chemotherapeutic treatment.

scholarly journals Melatonin Inhibits Benzene-Induced Lipid Peroxidation in Rat Liver

2010 ◽  
Vol 61 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Seema Sharma ◽  
Suresh Rana
Keyword(s):  
Lipid Peroxidation ◽  
Single Dose ◽  
Rat Liver ◽  
Treated Group ◽  
Melatonin Treatment ◽  
Liver Histopathology ◽  
Microsomal Lipid Peroxidation ◽  
Significant Difference ◽  
Mitochondrial Lipid

Melatonin Inhibits Benzene-Induced Lipid Peroxidation in Rat LiverWe studied the antioxidative role of melatonin against benzene toxicity in rat liver. The inhibition of mitochondrial and microsomal lipid peroxidation differed between 24-hour (single-dose), 15-day, and 30-day treatments. Inhibition of mitochondrial lipid peroxidation was the highest after the single dose of melatonin, whereas highest microsomal inhibition was recorded after 30 days of melatonin treatment. No significant difference was recorded between 15-day and 30-day treatments. Cytochrome P 4502E1 (CYP 4502E1) activity declined after the single-dose and 15-day melatonin treatment in the benzene-treated group, but it rose again, though not significantly after 30 days of treatment. Liver histopathology generally supported these findings. Phenol concentration in the urine samples declined in melatonin and benzene-treated rats. Our results show that melatonin affects CYP 4502E1, which is responsible for benzene metabolism. Inhibition of its metabolism correlated with lower lipid peroxidation. In conclusion, melatonin was found to be protective against lipid peroxidation induced by benzene.

scholarly journals Therapeutic role of Prostaglandin E2 receptor 4 stimulation in inflammatory cardiomyopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.T Takakuma ◽  
M.N Nishii ◽  
R.S Saji ◽  
K.S Sakai ◽  
R.M Matsumura ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cardiac Dysfunction ◽  
Treated Group ◽  
Left Ventricular ◽  
Type Iii Collagen ◽  
Inflammatory Cardiomyopathy ◽  
Autoimmune Myocarditis ◽  
Prostaglandin E2 Receptor ◽  
Vehicle Treated Group

Abstract Background Prostaglandin E2 receptor 4 (EP4) plays a crucial role in inflammatory diseases. Inflammatory cardiomyopathy often leads to refractory heart failure. Purpose We aimed to evaluate the role of EP4 in the development of inflammatory cardiomyopathy. Methods Experimental autoimmune myocarditis (EAM) was induced by immunization with cardiac myosin in balb/c mice. EP4 selective antagonist (CJ-42794, Cayman Chemical: 30 mg/kg/day), EP4 selective agonist (20 mg/kg/day), both, or vehicle alone was daily administrated after the immunization. Cardiac function and dimensions were assessed by echocardiography. Blood pressure and heart rate were assessed with tail-cuff method. Cardiac inflammation and fibrosis were immunohistologically examined. Molecular examination was performed by RT-PCR and immunoblotting. Results Cardiac dysfunction and dilatation were worsened on day 21 in EP4 antagonist-treated group compared with in the vehicle-treated group, accompanied by an increase in cellular infiltration area (21.7±1.9 vs. 11.0±2.7%, P=0.0367, respectively). Conversely, cardiac dysfunction and dilatation were improved in EP4 agonist-treated group compared with in the vehicle-treated group (Left ventricular fractional shortening: 69±3% vs. 40±4%, P&lt;0.0001; Left ventricular systolic dimension: 0.7±0.1mm vs. 1.9±0.3mm, P=0.0007; respectively). These parameters did not show significant differences between both-treated group and the vehicle-treated group. The protective effect of EP4 stimulation in EAM was also kept on day 56. Moreover, cardiac fibrosis area as well as mRNA expressions of Type III collagen and brain natriuretic peptide in the bulk hearts was significantly reduced on day 56 in EP4 agonist-treated group compared with in the vehicle-treated group (12.3±2.4% vs. 24.7±3.0%, P=0.0278, respectively). Cardiac expression of phosphorylated smad 2/3 protein as well as TGF-β1 mRNA did not show significant differences between the 2 groups, while cardiac expression of RORgammat protein, the master regulator of Th17 immunity was increased in the EP4 antagonist-treated group. Conclusions EP4 activation negatively regulated the induction of cardiac autoimmunity, which alleviated cardiac dysfunction, dilatation, and fibrosis. EP4 may be a therapeutic target for preventing the development of inflammatory cardiomyopathy. FUNDunding Acknowledgement Type of funding sources: None.

Role of thioredoxin nitration in bleomycin-induced pulmonary fibrosis in rats

2016 ◽  
Vol 94 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Lei Wang ◽  
Yimin Song ◽  
Xiankui Li ◽  
Haizhou Guo ◽  
Guojun Zhang
Keyword(s):  
Single Dose ◽  
Pulmonary Fibrosis ◽  
Wistar Rats ◽  
Intratracheal Instillation ◽  
Treated Group ◽  
Control Group ◽  
Tyrosine Nitration ◽  
Male Wistar Rats ◽  
Phosphate Buffered Saline

Oxidant stimulation has been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our study aimed to investigate the role and mechanisms of thioredoxin (Trx) nitration during the development of IPF. A rat model of IPF was established by intratracheal instillation of bleomycin (BLM). Male Wistar rats were randomly distributed among the control group and BLM-treated group, in which rats were intratracheally instilled with a single dose of BLM (5.0 mg/kg body mass in 1.0 mL phosphate-buffered saline). At 7 or 28 days after instillation the rats were euthanized. Histopathological and biochemical examinations were performed. The activity and protein level of thioredoxin were assessed. The thioredoxin nitration level was determined using immunoprecipitation and immunoblotting techniques. Our results demonstrated that protein tyrosine nitration increased in the BLM-treated group compared with the control group. Trx activity decreased in the BLM group compared with control group, whereas Trx expression and nitration level increased dramatically in the BLM group compared with the control group. Our results indicated that Trx nitration might be involved in the pathogenesis of IPF.

scholarly journals Protective role of Broccoli powder against continuous ingestion of Escitalopram antidepressant drug induced hepatotoxicity in Swiss albino male mice

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Sneha Saxena ◽  
Lata Shahani ◽  
Pradeep Bhatnagar
Keyword(s):  
Antioxidant Enzymes ◽  
Antidepressant Drug ◽  
Treated Group ◽  
Protective Role ◽  
Positive Control ◽  
Control Group ◽  
Male Mice ◽  
Drug Induced ◽  
Histopathological Studies

<p>To investigate the protective role of broccoli powder “<em>Brassica Oleracea Italica</em>” against continuous ingestion of escitalopram antidepressant drug induced hepatotoxicity in Swiss albino male mice.</p><p>Mice were divided into different groups. Group1: Normal control (0.9% NaCl), Group 2: Escitalopram drug treated only (20 mg/kg), Group 3: Broccoli powder with Escitalopram drug treated (200 mg/kg + 20 mg/kg), Group 4: Olive oil vehicle control, Group 5: Carbon tetrachloride (CCl<sub>4</sub>) referenced as positive control (33 mg/kg), Group 6: Broccoli powder with CCl<sub>4</sub> treated (200 mg/kg + 33 mg/kg). The effect of these groups on liver tissue was studied after three different time periods for 4, 8 and 12 weeks.</p>The results showed that the treatment with escitalopram drug displayed significantly increased serum SGOT, SGPT, ALP level and alter liver antioxidant enzymes level (LPO, SOD and GSH) that are comparable with CCl<sub>4</sub>intoxicated group considered as positive control. Comparing escitalopram drug treated group with group that received both broccoli powder and escitalopram drug displayed a significant decrease in serum SGOT, SGPT, ALP levels and restored the level of antioxidant enzymes. The protective effect of broccoli powder on escitalopram drug induced hepatotoxicity was also supported by histopathological studies.<p> </p>

The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat erythrocytes: role of vitamins E and C

2007 ◽  
Vol 23 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Recep Sutcu ◽  
Irfan Altuntas ◽  
Bora Buyukvanli ◽  
Onur Akturk ◽  
Ozlem Ozturk ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Body Weight ◽  
Single Dose ◽  
Treated Group ◽  
Control Group ◽  
Antioxidant Enzyme Activities ◽  
Organophosphate Insecticide ◽  
Rat Erythrocytes ◽  
Vitamins E And C

Reactive oxygen species caused by organophosphates may be involved in the toxicity of various pesticides. Therefore, in this study, we aimed to investigate the effects of acute exposure to organophosphate insecticide diazinon (DI) and possible ameliorating role of vitamins E and C, with the following parameters: lipid peroxidation (LPO) and the activity of the glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in rat erythrocytes. The experimental groups were arranged as control group, DI-treated group (DI) and DI + vitamin E + vitamin C—treated group (DI + Vit). DI + Vit groups were treated orally with a single dose of 335 mg/kg DI body weight. Vitamins E and C were injected at doses of 150 mg/kg body weight intramuscular (in) and 200 mg/kg body weight intraperitoneal (ip), respectively, 30 min after the treatment of DI in DI + Vit group. Blood samples were taken 24 h after the DI. The results showed that DI administration caused to increase in LPO and the activities of SOD and GSH-Px enzymes in erythrocytes. Also, the combination of vitamins E and C decreased LPO and the activities of GSH-Px and SOD compared with the DI group. In conclusion, although treating rats with single dose DI increases LPO and antioxidant enzyme activities in erythrocytes, vitamins C and E combination can reduce LPO caused by DI. Toxicology and Industrial Health 2007; 23: 13—17.

Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Enzyme Activities ◽  
Treated Group ◽  
Control Group ◽  
Puromycin Aminonucleoside ◽  
Low Level ◽  
Key Enzyme

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

Attachment Styles, Physical Proximity, and Relational Satisfaction

2014 ◽  
Vol 4 (2) ◽  
pp. 106-112
Author(s):  
Anita Shrivastava ◽  
Andrea Burianova
Keyword(s):  
Attachment Styles ◽  
Romantic Relationship ◽  
Distinct Type ◽  
Relational Satisfaction ◽  
Long Distance ◽  
Avoidant Attachment ◽  
Geographic Separation ◽  
Relationship Of ◽  
Attachment Dimensions

This study aimed to explore the relationships between attachment styles, proximity, and relational satisfaction. This was achieved by assessing a distinct type of long distance romantic relationship of flying crews, compared with proximal (non-flying crew) romantic relationships. The responses of 139 expatriate professionals revealed significant associations between proximity and anxious and avoidant attachment dimensions. The role of the avoidant dimension in comparison with that of the anxious dimension was found to be a significant predictor of relational satisfaction. This study contributes significantly toward addressing the role of proximity and attachment in relational satisfaction in a new context of geographic separation.

PERSEPSI PEMAHAMAN PERANAN AUDITOR, ETIKA AUDITOR DAN INDEPENDENSI AUDITOR INTERNAL DALAM MEWUJUDKAN GOOD UNIVERSITY GOVERNANCE DENGAN GAYA KEPEMIMPINAN SEBAGAI VARIABEL MODERASI

2019 ◽  
Vol 4 (1) ◽  
pp. 474
Author(s):  
Fipitriany Any
Keyword(s):  
Leadership Style ◽  
University Governance ◽  
Primary Data ◽  
Study Program ◽  
Internal Auditor ◽  
Internal Auditors ◽  
Analysis Models ◽  
Relationship Of ◽  
Role Ethics

ABSTRACT The purpose of this study is to examine and analyze the influence of the role, ethics, and independence of internal auditors in implementing good university governance (GUG) with leadership style as a moderation variable. Multiple linear regression and moderation regression analysis models are used to test the hypothesis. The primary data are obtained through questionnaires that are distributed to the respondents, namely the dean and head of study program at the UniversitasBinaDarma and UniversitasMuhammadiyahPalembang. The results of this study indicate that the instruments in each variable proved to be valid and reliable. Based on the results of hypothesis testing, it can be seen that simultaneously the variable of role, ethics, and independence of internal auditors have positively and significantly effect in implementing good university governance (GUG). These results provide justification or endorsement of the theoretical truths used as the theoretical references of Stewardship Theory and Attitude and Behavioral Theory. Based on the partial test, role of auditor does not significantly affect the variable of GUG, but ethics and independence variable are found to be significant in influencing GUG. The leadership style is negative and insignificant in moderating the role of internal auditors and GUC and also the independence of internal auditor and GUC. The leadership style is found to be positive and insignificant in moderating the relationship of internal auditors’ ethics and GUC.Keywords        Role, Ethics, Independence, Internal Auditor, Leadership Style, Good University Governance  ABSTRAK Tujuan dari penelitian ini adalah untuk menguji dan menganalisis pengaruh peran, etika, dan independensi auditor internal dalam menerapkan good university governance (GUG) dengan gaya kepemimpinan sebagai variabel moderasi. Model analisis regresi linier berganda dan regresi moderasi digunakan untuk menguji hipotesis. Data primer diperoleh melalui kuesioner yang dibagikan kepada responden, yaitu dekan dan ketua program studi di Universitas Bina Darma dan Universitas MuhammadiyahPalembang. Hasil penelitian ini menunjukkan bahwa instrumen dalam setiap variabel terbukti valid dan dapat diandalkan. Berdasarkan hasil pengujian hipotesis dapat dilihat bahwa secara simultan variabel peran, etika, dan independensi auditor internal berpengaruh positif dan signifikan dalam penerapan good university governance (GUG). Hasil ini memberikan pembenaran atau pengesahan kebenaran teoretis yang digunakan sebagai referensi teoretis dari Teori Penatalayanan dan Teori Sikap dan Perilaku. Berdasarkan uji parsial, peran auditor tidak secara signifikan mempengaruhi variabel GUG, tetapi variabel etika dan independensi ditemukan signifikan dalam mempengaruhi GUG. Gaya kepemimpinan negatif dan tidak signifikan dalam memoderasi peran auditor internal dan GUC dan juga independensi auditor internal dan GUC. Gaya kepemimpinan ditemukan menjadi positif dan tidak signifikan dalam memoderasi hubungan etika auditor internal dan GUC Kata Kunci            Peran, Etika, Independensi, Auditor Internal, Gaya Kepemimpinan, Tata Kelola Universitas

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