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Evaluation of Potentiation Effect of Omega-3 Fatty Acid on the Antidepressant Efficacy of Escitalopram in Albino Rats.

Depression is a mental disorder which is common, manifesting with depressed mood, anhedonia, lethargy, feelings of guilt or low self-esteem, disturbed sleep or appetite and poor concentration. It is estimated by the World Health Organisation that depression affects approximately 350 million people worldwide is associated with increasing morbidity [1]. A recent study has shown that depression is one of the ten leading causes of disabilities affecting up to 21% of the world population and will be the second leading cause of disability adjusted life years (DALY) by 2020 [2].

It has high impact on social and economic aspect, due to massive decrease in work productivity and increased usage of health care [3]. Enhancement of monoaminergic neurotransmisssion is the current pharmacological treatment of depression. However, despite its widespread use in clinical practice, it has challenges like onset of action, poor efficacy and presence of side effects [4,5]. Contrary to expectations, existing therapeutic options are effective in only one-third of depressed patients. Moreover, the time required for its maximal antidepressant activity is approximately 3-4 weeks [6]. Furthermore, single agent does not have more than 30% of remission rates [7,8].

Majority of patients have low compliance due to side effects and refuse to take antidepressants in appropriate doses. Therefore, the identification of novel drug or novel treatment combination with drugs that augment the efficacy of antidepressant is still needed. Role of nutrition has found greater role in depressive disorder as good amount of nutrients are essential for healthy mood [9-13]. Nutrients are essential for optimal production of neurotransmitters influencing mood [14]. There are reports mentioning lower concentration of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) in depressed individuals as compared to non-depressed individuals [15,16].

Meta-analytic reviews [17-19] and several clinical trials [20-24] have reported an antidepressant effect of Polyunsaturated fatty acids (PUFAs). There is increased evidence from animal as well as human studies showing omega-3 fatty acids may play an etiological role in several inflammatory, autoimmune and neuropsychiatric disorders [25,26].

Hence this study was conducted with an aim to explore the possible effect of omega-3 fatty acids in depression models. It was compared aith a standard antidepressant escitalopram, a selective serotonin reuptake inhibitor used in India [27]. Also their combination is used to study the role of omega-3 fatty acids inpotentiating efficacy of escitalopram.

MATERIALS AND METHOD

Animals

Sixty Albino Wistar rats of either sex (from Central animal house, KMC, Manipal) were used in the study. The rats used age 3-4 months and weight 150-250 gm at the beginning of the experimental procedure. Animals were housed three-four per cage in polycarbonate cages (28 x 17 x 12 cm). Except during testing, the animals were provided with pellet diet and water ad libitum throughout the study. Rats were maintained on a 12 h light (0700-1900 h)-12 h dark cycle at the ambient temperature of 25 [+ or -] 2ae%C and relative controlled humidity. They were allowed to acclimatize for a week before the onset of the experiment. Experiment was conducted in accordance with the Good laboratory practice (GLP) guidelines and CPCSEA guidelines after obtaining approval from Institutional Animal Ethics Committee IAEC/KMC/79/2015 dated 25-09-2015.

Drugs

Escitalopram and omega-3 fatty acids were obtained from local pharmacy.

1) Escitalopram: 10 mg per kg and 5 mg per kg.

2) Omega-3 Fatty Acid: 500 mg per kg.

Study design

In both acute and chronic studies, the role of omega-3 fatty acids was evaluated alone and in combination with escitalopram.

Acute Study

There were total five groups, in each group 6 rats. Drugs were administered for 7 days as follows:

Group 1 (Control)-2% Gum Acacia orally 23.5 and 1 h before the test.

Group 2 (Escitalopram)-Escitalopram dissolved in 2% Gum acacia in a dose of 10 mg/kg orally 23.5 and 1 h before the test.

Group 3 (Omega-3 FA)-omega-3 fatty acids 500 mg/kg in 2% Gum acacia orally 2 h before the test.

Group 4 (Escitalopram plus omega-3 FA)-Rats were given omega-3 fatty acids in a dose of 500 mg/kg orally 2 h before the test and escitalopram dissolved in 2% Gum acacia in a dose of 10 mg/ kg orally 23.5 and 1 h before the test.

Group 5 (Escitalopram plus omega-3 FA)-This group test the efficacy and augmentation effect of omega-3 FA with sub therapeutic level of escitalopram. Rats were administered with omega-3 fatty acids in a dose of 500 mg/kg orally 2 h before the test and escitalopram dissolved in 2% Gum acacia in a dose of 5 mg/kg orally 23.5 and 1 h before the test.
To test Omega-3 Fatty Acids Potentiation of the Antidepressant
Efficacy of Escitalopram

Groups    Drugs Route: oral route            Dose

Group 1   Control group                      2% Gum acacia
Group 2   Escitalopram group                 10mg/kg
Group 3   Omega-3 FA group                   500mg/kg
Group 4   Omega-3 FA + Escitalopram group    500mg/kg + 10 mg/kg
Group 5   Omega-3 FA + Escitalopram group    500mg/kg + 5mg/kg

Groups    Number of Rats

Group 1   6
Group 2   6
Group 3   6
Group 4   6
Group 5   6


Chronic Study

The schedule of drug administration was similar to acute study except that in chronic study omega-3 fatty acids was given 500 mg/kg orally for 28 days prior to the test both alone, as well as in combination with escitalopram. Two hours before the test, the last dose of omega-3 fatty acids was given.
To test Omega-3 Fatty Acids Potentiation of the Antidepressant
Efficacy of Escitalopram

Groups    DrugsRoute: oral route             Dose

Group 1   Control group                      2% Gum acacia
Group 2   Escitalopram group                 10mg/kg
Group 3   Omega-3 FA group                   500mg/kg
Group 4   Omega-3 FA + Escitalopram group    500mg/kg + 10 mg/kg
Group 5   Omega-3 FA + Escitalopram group    500mg/kg + 5mg/kg

Groups    Number of Rats

Group 1   6
Group 2   6
Group 3   6
Group 4   6
Group 5   6


Experiments

Forced swimming test (FST)

Porsolt et al. developed this model for antidepressant activity [28]. Rats had to swim in a glass cylinder filled with water up to 30 cm at 25C. They were trained for a 15-min pretest swim followed by a 5-min test swim session next day. After the swim session, rats were removed from water, and after 20 min were returned to their cages. After each test, the cylinders were washed completely. In pretest session, rats are active. After 2-3 min activity decreases to produce immobility, it keeps its head above water. This immobility is attenuated by antidepressants. In the test session, the behavior of rats were judged in blocks of 5 s for: immobility, swimming & climbing. The experiment was video recorded and the behavioral scoring was done.

Open-field test

This test was used to assess the ambulatory behavior [29]. The instrument consist of a wooden box (40cm x 60cm x 50cm), its floor was divided into 12 equal rectangles. At the initiation of each trial, a rat was placed in the left corner and was allowed to freely explore. In a 6 min session, the number of rectangles crossed with all paws were counted. The room was dimly lit to prevent anxiety behavior. In between the tests, the instrument was cleaned with 10% ethanol to avoid bias.

Splash test

This test was performed ten minutes after the open-field test, [30] with minor modifications. Ten percent sucrose solution was squirted on the dorsum of a rat placed individually in clear plexiglass boxes (9 x 7 x 11 cm). The sucrose solution dirties the rat fur, due to its viscosity and initiates grooming behavior in animals which was recorded for 5 min as an index of self-care and motivational behavior. To hide animal clues, the apparatus was cleaned with a 10% ethanol.

Neurochemical analysis

After conducting the experiment, rats were sacrified and blood was used for testing--

1. Reduced glutathione (GSH)

2. Malondialdehyde (MDA)

Statistical Analysis

P value <0.05 was taken as significant value was calculated by One-way ANOVA followed by Tukey's post-hoc test.

RESULTS

Acute study

Forced swimming test

Effect of escitalopram and omega-3 fatty acid on forced swimming test

Table 1 shows the results of forced swimming test done at 1 week. One count is duration of 5 sec. The standard group (escitalopram) showed a significant reduction in the counts of immobility (23.00 [+ or -] 1.06, p<0.05) along with a significant increase in the counts of swimming (25.00 [+ or -] 1.26, p<0.05) compared to the control group. However, the Omega 3 FA group did not show any significant difference in the counts of immobility, counts of swimming and counts of climbing. The escitalopram 10mg + omega 3 FA group as well as the escitalopram 5mg + omega 3 FA group showed a significant reduction in the counts of immobility (21.00 [+ or -] 0.86, p<0.001; 24.00 [+ or -] 0.73, p<0.05 respectively) with a significant increase swimming counts in both the groups (24.00 [+ or -] 1.06, p<0.05; 24.00 [+ or -] 0.73, p<0.05) when compared to the control and escitalopram group. There were no significant increase in climbing counts in any of the groups when compared to control.

Open field test

Effect of escitalopram and omega-3 fatty acid on open field test

Table 2 shows the results of the open field test done at 1 week. The above results does not show any significant difference in the number of entries in any of the groups when compared with control and the standard treatment group (escitalopram) (p>0.05).

Splash test

Effect of escitalopram and omega-3 fatty acid on splash test

Table 3 shows the splash test done at 1 week. It indicates that there is a significant difference in the time taken by the escitalopram 10mg+omega 3 FA group and escitalopram 5 mg+ omega 3 group when compared to control (163.00 [+ or -] 3.25, p<0.001 and 174.83 [+ or -] 3.27, p< 0.05 along with a significant reduction in time taken by the escitalopram 10mg + omega 3 group when compared with the standard treatment group (escitalopram) (163.00 [+ or -] 3.25, p<0.05).

Effect of escitalopram and omega-3 fatty acid on MDA

As shown in table 4 and figure 4 there was no significant difference among the control group and the test groups p<0.005.

Effect of escitalopram and omega-3 fatty acid on GSH

Table 5 shows the GSH levels at 1 week. Levels of glutathione reductase was significantly more in the escitalopram group (1.327 [+ or -] 0.015, p<0.05 and significantly increase in GSH in test groups, escitalopram 10mg+omega-3 (1.525 [+ or -] 0.017; p<0.05) and escitalopram 5 mg+omega-3 FA (1.345 [+ or -] 0.014; p<0.05) compared to control group

Chronic study

Forced swimming test

Effect of escitalopram and omega-3 fatty acid on forced swimming test

Table 6 shows the results of forced swimming test done at 4th week. The standard group (escitalopram) showed a significant reduction in the counts of immobility (21.00 [+ or -] 1.43, p<0.01) along with a significant increase in the counts of swimming (26.00 [+ or -] 1.06, p<0.01) compared to the control group. However, the omega 3 FA group did not show any significant difference in the counts of immobility, counts of swimming and counts of climbing. The escitalopram 10mg + omega 3 group as well as the escitalopram 5mg + omega 3 FA group showed a significant reduction in the counts of immobility (15.00 [+ or -] 0.73, p<0.001; 17.00 [+ or -] 0.58, p<0.01 respectively) with a significant increase swimming counts in both the groups (27.33 [+ or -] 1.30, p<0.05; 27.00 [+ or -] 1.24- p<0.01 respectively) when compared to the control and escitalopram group. There were no significant increase in climbing counts in any of the groups when compared to control.

Open field test

Effect of escitalopram and omega-3 fatty acid on open field test

Table 7. The number of entries increased significantly in the standard group escitalopram (44.00 [+ or -] 1.26; p<0.05) when compared with control along with significant increase in the number of entries in the escitalopram 10mg+omega-3 FA (47.00 [+ or -] 2.67; p<0.05) group when compared to control.

Splash test

Effect of escitalopram and omega-3 fatty acid on splash test

As shown in table 8 there was a significant decrease in time in test groups escitalopram (182.00 [+ or -] 5.46; p<0.05), escitalopram 10mg+omega-3 (154.00 [+ or -] 2.12; p<0.001) and escitalopram 5mg+omega-3(168.00 [+ or -] 4.03; p<0.001) when compared to control.

Effect of escitalopram and omega-3 fatty acid on MDA

As shown in table 9 and figure 9 there was significant increase in MDA in the test group escitalopram 10mg+ omega-3 (0.100 [+ or -] 0.003; p<0.05) when compared with the control.

Effect of escitalopram and omega-3 fatty acid on GSH

groups escitalopram (1.410[+ or -]0.014; p<0.001). The test groups escitalopram 10mg+omega-3 (1.625 [+ or -] 0.017; p<0.001) and ecitalopram 5mg+omega-3(1.445 [+ or -] 0.014; p<0.001) also showed a significant increase in GSH when compared to the control group.

DISCUSSION

The present study shows that Omega-3 fatty acids have antidepressant activity and have shown significant antidepressant efficacy in their combination with escitalopram. The study was divided into 2 parts acute (1 week) and chronic study (4 weeks). The results showed that omega-3 has no effect in short term either alone or in potentiating the escitalopram but in chronic study done over 4 weeks it showed potentiation effect with escitalopram.

The results are consistent with that of previous studies which have reported good efficacy of omega-3 supplementation with antidepressants in uncomplicated MDD. [21,22,31,32] The present study shows the antidepressant effect of omega-3 fatty acids, and its combination with escitalopram will potentiate the antidepressant efficacy than the standard drug escitalopram alone.

The suggestive possible mechanisms are as follows. Inflammatory processes are linked with depression. Omega-3 fatty acids reduce the inflammatory mediators, also hasan effect on brain-derived neurotrophic factor, which gives neuroprotection, and enhances neurotransmission. [33] A third possible mechanism is omega-3 fatty acids maintain membrane integrity and fluidity [34]. Animal studies have shown involvement of omega-3 fatty acids in receptor functioning, neurotransmitter levels, and monoamine metabolism in depression. [35,36]

Proinflammatory cytokines such as interleukin-1 beta, interleukin-2, interleukin-6, interferon-gamma, and tumor necrosis factor-alpha lower precursor neurotransmitter levels, activate hypothalamic-pituitary axis, and alter neurotransmitter metabolism in the central nervous system. Increase in these cytokines are associated with severity of depression [37]. Different factors such as psychological stress, infection, trauma, allergies, and toxins increase the cytokines. Omega-3 fatty acids are inhibitors of these proinflammatory cytokines, although the precise mechanism is unclear [38]. Reports on (in vitro) experiments with mouse mast cells suggest that omega-3 fatty acids suppress prostaglandin E2, thromboxane A2 and histamine and improve depressive symptoms. (Kaneniwa and co-workers) [39].

There are literature evidences suggesting antidepressants can promote neurogenesis. [40,41]. Chronic treatment with omega-3 fatty acids increases brain-derived neurotrophic factor (BDNF), which play a role in the plasticity of adult nervous system [42,43]. This is brought about by increase in the cyclic AMP (cAMP) signal-transduction which increases of cAMP response element-binding protein (CREB) leading to increase in BDNF. Serum BDNF was found to correlate negatively with the severity of depressive symptoms [44-48]. Bourre [49] et al. mentioned that omega-3 fatty acids are essential central nervous system membrane components [50]. Any alterations in membrane lipids can alter function due to change in fluidity. Proteins are incorporated into the lipid bilayer and are sensitive to the lipid microenvironment. They act as receptors, enzymes, and transporters [51-53] For binding of neurotransmitter and for signalling within the cell an optimal fluidity is required [54].

Haag [55] suggested that there are straight carbon chains in saturated fatty acids. Cis-desaturation of a fatty acid results in more curved carbon chain due to insertion of cis-double bonds in the cell membrane there is curling of the hydrophobic ends of the kinked chains which results in incorporation of more space when it is built into cell membrane phospholipids, thereby increasing the fluidity and functionality of the cell membrane [56].

Omega fatty acids in neuronal membranes can modulate many of the signal transduction mechanisms Different neurotransmitters such as serotonin, catecholamines and acetylcholine interact with members of a heptahelical transmembrane receptor family (55, 57-58). Murphy et al. and Nicholas et al [59,60] have confirmed that omega-3 fatty acids can increase adenylyl cyclase activity, which drives the cAMP messenger system. This pathway is used by 5-HT1 (serotonin) receptors, alpha-2 adrenergic and beta-adrenergic receptors, and both D1 and D2 (dopamine) receptors. It is well known in depression there is decreased serotonergic neurotransmission, Omega-3 fatty acids increase the activity of adenyl cyclase and thus facilitate serotonergic transmission. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and increases 5-HT synaptic concentration, 5-HT signal transduction is operational via cAMP pathway, fluoxetine in combination with omega-3 fatty acids exerts augmented effect by utilizing this facilitated 5-HT pathway. SSRIs are associated with various serotonergic side effects such as anxiety, insomnia, sexual dysfunction, serotonin syndrome etc., while omega-3 fatty acids are free from any significant adverse effects. As a long-term nutritional supplement, the combination of escitalopram and omega-3 fatty acids can decrease the dose and duration of SSRI administered, it may prove beneficial for prevention of depression in susceptible population.

CONCLUSION

Omega-3 Fatty acid and escitalopram were used to demonstrate the effect of antidepressant action and potentiation effect of omega-3 fatty acid on escitalopram.

The study was divided in 2 parts acute and chronic. In acute study was significant potentiation effect seen in forced swimming test, splash test and GSH test. So, omega-3 fatty acid does not have antidepressant effect in short duration of activity. In chronic study all the test showed significant difference indicating omega-3 FA has potentiation effect in chronic use (28 days).

Based on the findings of the current study, we conclude that omega-3 has antidepressant activity in chronic use but not in acute duration. Omega-3 fatty acid can be considered as a part of therapeutic use along with escitalopram. Further preclinical and clinical studies may be required to assess the similar properties of omega-3 fatty acid.

ACKNOWLEDGEMENT

We acknowledge Manipal Academy of Higher Education for their support in conduct of this study.

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Amberkar Mohanbabu Vittalrao (1), Saurabh Agarwal (2), Meena Kumari Kamalkishore (1) * and Basavaraj Poojar (3)

(1) Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India-576104.

(2) Medical Science Liaison, Sanofi Pasteur India Pvt. Ltd, Dalibagh, Lucknow-226001, India.

(3) Basavaraj Poojar-Department of Pharmacology, Kasturba Medical College, Mangaluru, Manipal Academy of Higher Education, Manipal, Karnataka, India.

* Corresponding author E-mail-mini41178@yahoo.co.in

http://dx.doi.org/10.13005/bpj/1777

(Received: 20 June 2019; accepted: 16 September 2019)
Table 1. Forced swimming test done at 1 week, a-P<0.05 versus control
group, b-P<0.001 versus control group

Sl. No.           Group(n=6)             Counts of immobility
                                         (Mean [+ or -] S.E.M)

1.                  Control               30.00 [+ or -] 1.71
2.          Standard(escitalopram)        23.00 [+ or -] 1.06 (a)
3.                Omega-3 FA              27.00 [+ or -] 1.29
4.        Escitalopram10mg+Omega-3 FA     21.00 [+ or -] 0.86 (b)
5.        Escitalopram 5mg+Omega-3 FA     24.00 [+ or -] 0.73 (a)

Sl. No.     Counts of swimming       Counts of climbing
           (Mean [+ or -] S.E.M)    (Mean [+ or -] S.E.M)

1.        19.00 [+ or -] 0.73        12.00 [+ or -] 0.58
2.        25.00 [+ or -] 1.26 (a)    14.00 [+ or -] 0.58
3.        20.00 [+ or -] 1.06        12.00 [+ or -] 0.58
4.        24.00 [+ or -] 1.06 (a)    13.00 [+ or -] 0.58
5.        24.00 [+ or -] 0.73 (a)    13.00 [+ or -] 0.58

Table 2. Open field test done at 1 week

S.   Group(n=6)                      Number of entries
No                                 (Mean [+ or -] S.E.M)

1.   Control                        33.50 [+ or -] 1.31
2.   Escitalopram                   39.50 [+ or -] 3.10
3.   Omega-3                        29.17 [+ or -] 2.73
4.   Escitalopram10mg+omega-3 FA    40.33 [+ or -] 2.59
5.   Escitalopram 5mg+omega-3 FA    37.33 [+ or -] 1.76

Table 3. Splash test done at 1 week, a-P<0.05 versus group control,
b-denotes P<0.001 versus control, c-denotes the time in seconds of
escitalopram 10mg+ omega 3 group compared to escitalopram group;

S.    Group(n=6)                                Time in sec.
No.                                        (Mean [+ or -] S.E.M)

1.    Control                               201.00 [+ or -] 5.67
2.    Escitalopram                          187.00 [+ or -] 4.47
3.    Omega-3 FA                            201.33 [+ or -] 5.50
4.    Escitalaopram.10mg+ omega-3 FA     163.00 [+ or -] 3.25 (b,c)
5.    Escitalopram 5mg+ omega-3 FA        174.83 [+ or -] 3.27 (a)

Table 4. MDA test done at 1 week

S.      Group(n=6)                               MDA
No.                                     (Mean [+ or -] S.E.M)

1.      Control                         0.047 [+ or -] 0.003
2.      Escitalopram                    0.041 [+ or -] 0.001
3.      Omega-3                         0.045 [+ or -] 0.003
4.      Escitalopram.10mg+omega-3 FA    0.051 [+ or -] 0.002
5.      Escitalopram 5mg+omega-3 FA     0.041 [+ or -] 0.002

Table 5. GSH test done at 1 week, [(a)- p <0.001 versus control group]

S.    Group(n=6)                              GSH
No.                                  (Mean [+ or -] S.E.M)

1.    Control                         1.141 [+ or -] 0.013
2.    Escitalopram                    1.327 [+ or -] 0.015 (a)
3.    Omega-3 FA                      1.180 [+ or -] 0.007
4.    Escitalopram10mg+omega-3 FA     1.525 [+ or -] 0.017 (a)
5.    Escitalopram 5mg+omega-3 FA     1.345 [+ or -] 0.014 (a)

Table 7. Open field test done at 4 weeks [(a)- P<0.05 versus
control group]

S.   Group(n=6)                         Number of entries
No                                    (Mean [+ or -] S.E.M)

1.   Control                           34.67 [+ or -] 1.70
2.   Escitalopram                      44.00 [+ or -] 1.26 (a)
3.   Omega-3 FA                        41.16 [+ or -] 1.90
4.   Escitalopram 10mg+omega-3 FA      47.00 [+ or -] 2.67 (a)
5.   Escitalopram 5mg+omega-3 FA       39.00 [+ or -] 2.62

Table 6. Forced swimming test done at 4 weeks [(a)- P<0.001
versus control group]

S.   Group(n=6)                        Count of immobility
No.                                   (Mean [+ or -] S.E.M)

1.   Control                           29.00 [+ or -] 0.96
2.   Escitalopram                      21.00 [+ or -] 1.43 (a)
3.   Omega-3 FA                        25.00 [+ or -] 0.89
4.   Escitalopram 10mg+omega-3 FA      15.00 [+ or -] 0.73 (a)
5.   Escitalopram 5mg+omega-3 FA       17.00 [+ or -] 0.58 (a)

S.   Group(n=6)                          Count of swimming
No.                                    (Mean [+ or -] S.E.M)

1.   Control                            17.00 [+ or -] 0.73
2.   Escitalopram                       26.00 [+ or -] 1.06 (a)
3.   Omega-3 FA                         23.00 [+ or -] 0.86
4.   Escitalopram 10mg+omega-3 FA       27.33 [+ or -] 1.30 (a)
5.   Escitalopram 5mg+omega-3 FA        27.00 [+ or -] 1.24 (a)

S.   Group(n=6)                        Counts of climbing
No.                                   (Mean [+ or -] S.E.M)

1.   Control                           12.00 [+ or -] 1.06
2.   Escitalopram                      13.50 [+ or -] 0.89
3.   Omega-3 FA                        13.00 [+ or -] 1.13
4.   Escitalopram 10mg+omega-3 FA      14.33 [+ or -] 1.20
5.   Escitalopram 5mg+omega-3 FA       13.50 [+ or -] 0.96

Table 8. Splash test done at 4 weeks [(a)-p<0.05 versus control
group; (b)-p<0.001 versus control group]

S.    Group (n=6)                          Time in secs.
No.                                    (Mean [+ or -] S.E.M)

1.    Control                         210.00 [+ or -] 11.94
2.    Escitalopram                    182.00 [+ or -] 5.46 (a)
3.    Omega-3FA                       196.00 [+ or -] 4.70
4.    Escitalopram 10mg+omega-3 FA    154.00 [+ or -] 2.12 (b)
5.    Escitalopram 5mg+omega-3 FA     168.00 [+ or -] 4.03 (b)

Table 9. MDA test done at 4 weeks [(a)- P<0.05 versus control group]

S.    Group(n=6)                                MDA
No.                                   (Mean [+ or -] S.E.M)

1.    Control                         0.055 [+ or -] 0.005
2.    Escitalopram                    0.048 [+ or -] 0.004
3.    Omega-3 FA                      0.068 [+ or -] 0.008
4.    Escitalopram 10mg+omega-3 FA    0.100 [+ or -] 0.003 (a)
5.    Escitalopram 5mg+omega-3 FA     0.058 [+ or -] 0.012

Table 10. GSH test done at 1week [(a)- P<0.001 versus control group]

S. No.   Group(n=6)                      GSH (Mean [+ or -] S.E.M)

1.       Control                         1.242 [+ or -] 0.013
2.       Escitalopram                    1.410 [+ or -] 0.014 (a)
3.       Omega-3 FA                      1.280 [+ or -] 0.007
4.       Escitalopram 10mg+omega-3 FA    1.625 [+ or -] 0.017 (a)
5.       Escitalopram 5mg+omega-3 FA     1.445 [+ or -] 0.014 (a)
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Author:Vittalrao, Amberkar Mohanbabu; Agarwal, Saurabh; Kamalkishore, Meena Kumari; Poojar, Basavaraj
Publication:Biomedical and Pharmacology Journal
Geographic Code:9INDI
Date:Sep 1, 2019
Words:5714
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