ArticlePDF Available

Abstract and Figures

Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative damages in hepatic tissue. This study assessed the effect of royal jelly (RJ) supplementation on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/Kg) was administered for fourteen days and stressed groups were submitted to chronic stress from the seventh day. The results showed that RJ supplementation decreases corticosterone levels and improves glycemia control after stress induction. RJ supplementation also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus, RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant system in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ.
Content may be subject to copyright.
RESEARCH ARTICLE
Adaptogenic potential of royal jelly in liver of
rats exposed to chronic stress
Douglas Carvalho Caixeta
1
, Renata Roland Teixeira
1
, Leonardo Gomes Peixoto
1
, Helen
Lara Machado
1
, Nathalia Belele Baptista
1
, Adriele Vieira de Souza
1
, Danielle Diniz Vilela
1
,
Celso Rodrigues Franci
2
, Foued Salmen Espindola
1
*
1Institute of Biotechnology, Federal University of Uberla
ˆndia, Uberla
ˆndia, Minas Gerais, Brazil,
2Department of Physiology, University of São Paulo, Ribeirão Preto, Minas Gerais, Brazil
These authors contributed equally to this work.
*foued@ufu.br
Abstract
Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative
damages in hepatic tissue. This study assessed the effect of royal jelly (RJ) supplementa-
tion on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system
in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-
stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/
Kg) was administered for fourteen days and stressed groups were submitted to chronic
stress from the seventh day. The results showed that RJ supplementation decreases corti-
costerone levels and improves glycemia control after stress induction. RJ supplementation
also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxi-
dant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus,
RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant sys-
tem in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ.
Introduction
The adaptive response to stress is characterized by psychophysiological adaptations of an
organism to restore homeostasis [1]. It is well documented that chronic restraint and cold
stress effectively mimics physical and psychological stress [2], elevate metabolic rate and also
increase production of reactive oxygen species (ROS). Physical and psychological stress acti-
vates the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system
(ANS), increasing plasma glucocorticoid levels [3]. Increased corticosterone levels were
observed in stress responses using the stress models, such as restraint and cold [2], immobiliza-
tion [4], cold [5], cold water immersion [5], electric foot shock [6] and social isolation stress
[7]. Corticosterone increases gluconeogenesis and hepatic glycogenolysis in rats, resulting in
an increase in the availability of metabolic substrates [8].
A metabolic byproduct of stress-induced increase in energy production is the formation of
ROS [9] e.g. hydrogen peroxide (H
2
O
2
), hydroxyl radicals (HO
) and superoxide anion radi-
cals (O2
), which cause lipid peroxidation. In addition, the increased corticosterone levels
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 1 / 13
a1111111111
a1111111111
a1111111111
a1111111111
a1111111111
OPEN ACCESS
Citation: Caixeta DC, Teixeira RR, Peixoto LG,
Machado HL, Baptista NB, de Souza AV, et al.
(2018) Adaptogenic potential of royal jelly in liver of
rats exposed to chronic stress. PLoS ONE 13(1):
e0191889. https://doi.org/10.1371/journal.
pone.0191889
Editor: M. Faadiel Essop, Stellenbosch University,
SOUTH AFRICA
Received: August 3, 2017
Accepted: January 12, 2018
Published: January 29, 2018
Copyright: ©2018 Caixeta et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: All relevant data are
within the paper.
Funding: The authors received funding support for
this work by Foundation of Support Research of
the State of Minas Gerais (FAPEMIG), National
Council for Scientific and Technological
Development (CNPq) and Coordination for the
Improvement of Higher Education Personnel
(CAPES). The funders had no role in study design,
data collection and analysis, decision to publish, or
preparation of the manuscript.
trigger ROS production and promote redox imbalance in different tissues of the body [10,11].
Oxidative stress also associated with physical stress induces changes in antioxidant defense sys-
tems [11]. Therefore, to neutralize reactive oxygen species, the body uses mainly enzymatic
and non-enzymatic antioxidant defense system [12].
Several studies have investigated whether nutraceutical supplementation results in enhance-
ment of the antioxidant defense system. In relation to stress management, nutraceutical sup-
plements have been used as an adaptogenic agent to support the body’s adaptation in stressful
situations [13]. Thus, royal jelly (RJ) could be used as a nutraceutical product. RJ is secreted by
the mandibular and hypopharyngeal glands of worker bees (Apis mellifera L.). Royal Jelly com-
position includes major royal jelly proteins, free amino acids, sugars, vitamins (B1, B2, B6,
folic acid, pantothenic acid, nicotinic acid, and biotin) and lipids such as 10-hydroxy-2-dece-
noic acid (HDA-10). The RJ has several biological properties including anti-inflammatory
[14], vasodilator and hypotensive [15], antimicrobial [16], immunomodulatory [17], hypocho-
lesterolemic [18] and antioxidant [19] activities.
In a previous study from our research group, we demonstrated a neuroprotective effect of
royal jelly supplementation and a reduction of corticosterone levels in a stress condition [20].
With these interesting results, the interest arose to evaluate the effect of the royal jelly supple-
mentation on the liver, which is a central organ of metabolism and is related to the synthesis of
cholesterol, a precursor of corticosterone. As well as, to investigate the effect of RJ supplemen-
tation on a non-stressful situation. As glucocorticoids have direct and indirect modulatory
roles in oxidative stress [9], our hypothesis was that RJ could decrease corticosterone levels,
even in the absence of stress, and oxidative stress in liver tissue. Thus, the aim of the study was
to evaluate the adaptogenic and antioxidant effect of RJ supplementation in rats submitted to
chronic stress induced by restraint and cold.
Materials and methods
Samples
RJ was imported from China and provided by Apia
´rio Girassol Ltda. (Uberla
ˆndia—MG, Bra-
zil). The centesimal analysis of the royal jelly was carried out by the Laboratory of Bromatology
and Animal Nutrition of the Federal University of Uberla
ˆndia. The royal jelly has 67% of
humidity and 33% of dry matter, of these, 14.19% are crude protein, 2.01% are lipids, 0.87%
are ash and 15.93% are carbohydrates. The RJ was stored at -20˚C until use. Daily, 200 mg/kg
b.w. of RJ samples were prepared for use in supplementation.
Animals
Wistar rats (207–250g) were obtained and kept in the Center for Bioterism and Experimenta-
tion at the Federal University of Uberla
ˆndia, Uberla
ˆndia, Brazil. Animals were kept in con-
trolled conditions (22 ±1 ˚C, humidity 60% ±5 and 12-hour light-dark cycles– 6:00/18:00 h
lights on/off) with a standard diet and water ad libitum. Body weight was measured at the
beginning and end of the study, while water and food intake per animal were measured daily.
All experimental procedures were approved and conducted by the Brazilian Society of Labora-
tory Animal Science and the Ethics Committee for Animal Research of the Federal University
of Uberla
ˆndia, Brazil (CEUA No. 047/14).
Induction of stress by restraint and cold
Animals were randomly allocated into four groups (n = 10/group): no stress (NS); no stress
supplemented with royal jelly (NSRJ); stress (S); and stress supplemented with royal jelly
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 2 / 13
Competing interests: The authors have declared
that no competing interests exist.
(SRJ). The animals were exposed to stress by restraint and cold, using the method of Paula-
Freire et al. [21]. These method effectively mimics a condition of physical and psychological
stress [2]. The restraint stress was carried out using individual acrylic hemicylindrical plastic
tubes (4.5 cm diameter, 12 cm long) for 2 hours daily in the morning (8:00 h– 10:00 h.). The
cold stress was carried at 10˚C for 2 hours daily in the afternoon (16:00 h– 18:00 h).
Supplementation with RJ began seven days before the stress sessions with subsequent sup-
plementation for seven more days during the period of stress induction [21]. RJ was adminis-
tered by oral gavage 45 minutes before the stress session. The NS and S rats received a placebo
(water) and the NS and NSRJ rats were not exposed to stressors.
On the fourteenth day, animals were exposed to the two stressors simultaneously for 2
hours [21] until euthanasia. Glucose levels were measured before and after this last session of
stress (Sb—stress before; SRJb—stress supplemented with RJ before stress session; Sa—stress
after; SRJa—stress supplemented with RJ after stress session) by puncturing the tail vein, using
reactive strips (Accu-Chek Performa, Roche Diagnostic Systems, Basel, Switzerland).
The NS, NSRJ, S, SRJ rats were anaesthetized with ketamine (90 mg/kg) and xylazine (20
mg/kg), in accordance the methods of Arnold and Langhans, 2010 [22]. All groups were sub-
jected to the same manipulation procedure. Plasma samples were used to assess corticosterone
levels and hepatic enzyme activities, whereas liver tissues were used for oxidative stress
analysis.
Determination of corticosterone levels by radioimmunoassay
Blood samples were collected (08:00 h– 11:00 h in heparinized plastic tubes and centrifuged at
1200g at 4˚C for 15 min.) after the last session of stress via cardiac puncture in the right ventri-
cle. Plasma was separated and frozen at -20˚C until the assay. Radioimmunoassay (RIA) used
H3-corticosterone from NEN Life Science Products (Boston, USA) and a standard reference
specific antibody from Sigma (St. Louis, MO, USA). Corticosterone was used to measure triti-
ated recovery [23]. The intra-assay error was 4.5% and the minimum detectable dose was 0.08
ng/ml.
Hepatic enzymes activities in plasma
Aspartate transaminase (AST), alanine transaminase (ALT), γ-glutamyl transferase (GGT) and
alkaline phosphatase (ALP) were measured at the Laboratory of Clinical Analyses, School of
Veterinary Medicine, Federal University of Uberla
ˆndia, using an automatic analyzer (Cobas
Mira, Roche Diagnostic Systems, Basel—Switzerland), by using commercial kits (Labtest Diag-
no
´stica, Lagoa Santa—Brazil).
Sample collection and tissue preparation
The liver tissues were quickly removed, separated in lobes, washed (NaCl 0.9% buffer) and
immersed in liquid nitrogen. Then, the same part of liver tissues were thawed and homoge-
nized in phosphate buffer (1:10 w/v, pH 7.4). The homogenates were centrifuged at 800 x g for
15 min at 4˚C, and the total protein concentration in the supernatant samples was measured,
according to the Bradford assay [24].
Oxidative stress marker analysis
Thiobarbituric acid reactive substances (TBARS). Lipid peroxidation was measured by
the reaction between malondialdehyde in the liver samples (MDA) and thiobarbituric acid
(0.67% TBA). Organic-phase fluorescence was evaluated at 515 nm (excitation) and at 553 nm
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 3 / 13
(emission). A MDA standard curve allowed the quantification of the compound in the samples
by linear regression [25]. TBARS levels were calculated as nmol TBARS/mg of protein.
Total antioxidant capacity (FRAP). Total antioxidant capacity was evaluated by the
capacity of the samples to reduce Fe
+3
to Fe
+2
, which was then chelated by TPTZ (2,4,6-Tris
(2-pyridyl)-s-triazine) in order to form the deep-blue colored Fe
+2
-TPTZ complex [25]. This
complex was measured in a spectrophotometer at 593 nm.
Superoxide dismutase (SOD) activity. SOD activity was measured by the inhibition
autoxidative capacity of pyrogallol. The SOD activity was evaluated using a spectrophotometer
at 420 nm. A calibration curve was constructed using SOD as standard. A 50% inhibition of
autoxidation of pyrogallol was defined as one SOD unit [25].
Reduced glutathione (GSH). The protein content of the samples was initially precipitated
by metaphosphoric acid (MPA) at the ratio of 1:1 (homogenate/MPA). The samples were cen-
trifuged at 7000xg for 10 minutes. The supernatant was collected and mixed with sodium
phosphate buffer (100 mM, pH 8.0), containing EDTA (5mM) and ortho-phthaldialdehyde (1
mg/mL in methanol). The mixture was incubated in the dark at room temperature for 15 min
and fluorescence was measured at 350 nm (excitation) and 420 nm (emission). A standard
curve of GSH (0.001–0.1 mM) was used for linear regression [25].
Glutathione peroxidase (GPx) activity. To measure the glutathione peroxidase activity,
the homogenate was incubated with GPx buffer (100 mM potassium phosphate containing 1
mM EDTA, pH7.7), sodium azide (40 mM), GSH (diluted in 5% metaphosphoric acid), GR
(diluted in GPx buffer), NADPH (diluted with sodium bicarbonate 5%) and tert-butyl (0.5
mM). The reduction in NADPH concentration was evaluated for 10 minutes in a spectropho-
tometer, at 340 nm [25].
Glutathione reductase (GR) activity. GR activity was evaluated using oxidized glutathi-
one (GSSG) and nicotinamide adenine dinucleotide phosphate (NADPH) as substrates. The
activity of the enzyme was determined using sodium phosphate buffer (200 mM, pH 7.5),
EDTA (6.3 mM), GSSG (1 mM), NADPH (1 mM) and the samples [25]. The consumption of
NADPH was measured at 340 nm for 10 minutes. A GR unit is defined as one μmol of reduced
GSSG per minute. The specific activity was calculated as U/mg of protein.
Glucose-6-phosphate dehydrogenase (G6PDH) activity. The activity of glucose-6-phos-
phate dehydrogenase was monitored by the production of NADPH with a consequent increase
in absorbance at 340nm. The samples were incubated with Tris-HCl buffer (100mM, pH 7.5),
magnesium chloride (MgCl
2
, 2 M), NADP
+
(0.5 mM) and glucose-6-phosphate (1mM). The
kinetic readings were monitored for ten minutes [25].
Statistical analyses
Data were used as independent variables (stress by restraint and cold) and as the dependent
variables (body weight, water and food intake, biochemical parameters and oxidative stress).
The data were analyzed using the one-way analysis of variance (ANOVA) followed by the
Tukey Multiple Comparison as a post-hoc test. All analyses were performed using the software
GraphPad Prism (GraphPad Prism version 6.00 for Windows; GraphPad Software, San Diego,
CA, USA). Outliers were detected by performing Grubb’s test using an online GraphPad out-
lier calculator (http://graphpad.com/quickcalcs/Grubbs1.cfm). Only values of p <0.05 were
considered significant. Results were expressed as mean ±SEM.
Results
Table 1 shows the effect of RJ supplementation on body weight, water and food intake and
hepatic enzyme activities in the plasma of restraint and cold stressed rats. S, NSRJ and SRJ
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 4 / 13
decreased the body weight compared to NS (F
3, 33
= 7.757, p <0.05, F
3, 33
= 7.757, p <0.05;
F
3, 33
= 7.757, p <0.001, respectively), and no change was observed between S and SRJ rats.
No significant difference was observed in the water or food intake among the groups. In addi-
tion, NSRJ and SRJ decreased the AST levels compared to NS (F
3, 29
= 17.64, p <0.001; F
3, 29
=
17.64, p <0.01, respectively) and SRJ compared to S rats (F
3, 29
= 17.64, p <0.05), while ALT
was not different among the groups. S rats had increased GGT compared to NS (F
3, 27
= 14.17,
p<0.001) whereas SRJ rats had decreased GGT levels compared to S rats (F
3, 27
= 14.17,
p<0.05). Furthermore, NSRJ and SRJ had decreased ALP levels compared to NS rats (F
3, 31
=
5.203, p <0.01; F
3, 31
= 5.203, p <0.05, respectively), whereas no change was observed in SRJ
compared to S rats or in S compared to NS rats.
Stress biomarkers were evaluated in plasma samples of NS, NSRJ, S and SRJ rats. Plasma
corticosterone levels increased in S compared to NS rats (F
3,28
= 14.56, p <0.05) whereas RJ
supplementation (NSRJ and SRJ) decreased corticosterone levels compared to NS (F
3,28
=
14.56, p <0.05) and S rats (F
3,28
= 14.56, p <0.001) (Fig 1A). Furthermore, blood glucose lev-
els did not differ in NSRJ and Sb compared to NS rats, whereas an increase was verified in Sa,
Table 1. The effect of the stress-induction by restraint and cold and supplementation of royal jelly on body weight, water intake, food intake and hepatic enzymes
activities in plasma.
Parameters NS NSRJ S SRJ
ΔBody weight (g) 51.11±2.54 38.97±2.0439.63±4.1932.22±2.14
Water intake (ml) 41.25±4.19 44.07±4.66 37.56±2.52 38.91±6.25
Food intake (g) 23.51±0.35 24.30±0.71 22.98±0.40 22.82±0.27
AST (U/L) 99.78±3.30 67.13±5.4197±1.19 83.44±3.24#
ALT (U/L) 47.5±4.03 46.38±2.19 48.22±1.66 53.44±2.91
GGT (U/L) 8.71±1.42 7.02±0.70 22.49±3.2514.16±1.59#
ALP (U/L) 336.2±38.04 223±16.35279±8.60 242.3±16.89
Note: Values are expressed as mean ±S.E.M (n = 10).
p<0. 05 vs NS rats;
#
p<0. 05 vs S rats.
No stress (NS), No stress supplemented with royal jelly (NSRJ), Stress(S) and Stress supplemented with royal jelly (SRJ); Aspartate transaminase (AST); Alanine
transaminase (ALT); γ-glutamyl transferase (GGT) and Alkaline phosphatase (ALP).
https://doi.org/10.1371/journal.pone.0191889.t001
Fig 1. Biomarkers of chronic stress in liver tissue of rats stressed by restraint andcold. Plasma corticosterone level after seven days of stress-induction (A). No
stress (NS), No Stress supplemented with Royal Jelly (NSRJ), Stress (S) and Stress supplemented with Royal Jelly (SRJ). Blood glucose level before and after the last
stress induction (B). No stress (NS), No Stress supplemented with Royal Jelly (NSRJ), Stress group before the last stress session (Sb), Stress group after the last stress
session (Sa), Stress group supplemented with RJ before the last stress session (SRJb), Stress group supplemented with RJ after the last stress session (SRJa). Pearson
correlation of mean values of corticosterone levels and blood glucose after the last stress-induction (C). Values are expressed as means ±SEM. p<0.05 vs NS,
# p <0.05 vs S, & p <0.05 vs Sb, § p <0.05 vs Sa (One-way ANOVA followed by Tukey test). Outliers were detected by performing Grubb’s test using an online
GraphPad outlier calculator (http://graphpad.com/quickcalcs/Grubbs1.cfm).
https://doi.org/10.1371/journal.pone.0191889.g001
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 5 / 13
SRJb and SRJa compared with both NS (F
5, 47
= 32.55, p <0.001) and between Sa and SRJa
compared to Sb rats (F
5, 47
= 32.55, p <0.001; F
5, 47
= 32.55, p <0.01, respectively). When gly-
cemia was compared among the stressed rats, SRJa (F
5, 47
= 32.55, p <0.05) and SRJb (F
5, 47
=
32.55, p <0.01) had decreased blood glucose levels compared with Sa rats, whereas no differ-
ence was observed between SRJb compared to Sb and SRJa rats (Fig 1B). In addition, Pearson
correlation between corticosterone levels and glycemia after the last stress induction showed a
strong positive correlation (r = 0.769, p = 0.001) (Fig 1C).
Fig 2 shows the oxidative stress status in liver tissue. Stressed rats (S) decreased the total
antioxidative capacity (FRAP) (F
3, 23
= 11.65, p <0.01) and increased lipid peroxidation
(TBARS) (F
3, 21
= 5.027, p <0.05) compared to NS rats. SRJ rats increased FRAP (F
3, 23
=
11.65, p <0.05) and decreased malondialdehyde levels (F
3, 21
= 5.027, p <0.05) compared to S
rats (Fig 2A and 2B). Pearson correlation between corticosterone and FRAP showed a negative
correlation (r = -0.756, p = 0.001), whereas a positive correlation (r = 0.666, p = 0.0019) was
observed between corticosterone and lipid peroxidation (Fig 2C and 2D).
Fig 2. Biomarkers of oxidative stress in liver tissue of rats stressed by restraint and cold.Total antioxidant capacity by FRAP method (A). Lipid
Peroxidation by TBARS method (B). No stress (NS), No Stress supplemented with Royal Jelly (NSRJ), Stress (S) and Stress supplemented with Royal Jelly
(SRJ). Values are expressed as mean±SEM, p<0.05 vs. NS, # p <0.05 vs. S (One-way ANOVA followed by Tukey test). Pearson correlation of FRAP and
TBARS (panels C and D) and means values of corticosterone levels. Outliers were detected by performing Grubb’s test using an online GraphPad outlier
calculator (http://graphpad.com/quickcalcs/Grubbs1.cfm).
https://doi.org/10.1371/journal.pone.0191889.g002
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 6 / 13
SOD enzyme activity in liver tissues is shown in Fig 3. The S rats displayed a decreased
SOD activity compared to NS rats (F
3, 40
= 18.18, p <0.05), whereas RJ supplementation
increased the SOD activity in SRJ groups compared to S rats (F
3, 40
= 18.18, p <0.001). Fur-
thermore, NSRJ rats increased the SOD compared to NS (F
3, 40
= 18.18, p <0.05) (Fig 3).
The glutathione defense system analysis in liver tissues is displayed in Fig 4. GSH content
was lower in S compared to NS (F
3, 51
= 17.65, p <0.001), whereas GR and G6PDH levels
were higher in S compared to NS (F
3, 21
= 20.42, p <0.05; F
3, 20
= 17.24, p <0.05, respectively).
No significant difference was observed in GPx activity in S rats compared with NS rats. In
addition, the glutathione defense system analysis of the RJ supplemented S rats showed an
increase in GSH content (F
3, 51
= 17.65, p <0.05), a decrease in the GR level (F
3, 21
= 20.42,
p<0.05), whereas no difference was observed in GPx and G6PDH activity compared to S rats.
Discussion
Studies have been carried out to assess agents that could prevent the damage to liver tissues
triggered by acute and chronic stress, which induce the formation of ROS followed by hepatic
injury [26]
,
[27]. In this study, the adaptogenic potential of RJ was assessed and associated with
the antioxidant activity and anti-stress capacity, to improve the organism’s adaptation to stress
induction and in absence of stress. Our results showed a decrease of corticosterone and blood
glucose levels, weight loss as well as an improvement in the antioxidative parameters in the
liver of stressed RJ-supplemented rats.
Stress promotes the activation of the HPA axis, thus stimulating the release of corticoste-
rone by the adrenal gland [3]. This increase in corticosterone mobilizes energy substrates in
liver tissues to maintain homeostasis in a stress situation [28]. In the present study, restraint
and cold stress not only augmented corticosterone levels, blood glucose levels and biomarkers
of oxidative stress, but also diminished the glutathione antioxidant defense system in the liver
tissues. Our results corroborate other studies that reported an increase of corticosterone levels
under several stress models such as restraint and cold, immobilization and cold, besides other
models of stress induction [2,46,20,29]. Besides that, we showed a decreased of the cortico-
sterone level associated with RJ supplementation, even in absence of stress. Teixeira et al.
Fig 3. Superoxide dismutase activity in liver tissue of rats stressed by immobilization and cold. No stress (NS), No
Stress supplemented with Royal Jelly (NSRJ), Stress (S) and Stress supplemented with Royal Jelly (SRJ). Values are
expressed as mean±SEM, p<0.05 vs. NS, # p <0.05 vs. S (One-way ANOVA followed by Tukey test). Outliers were
detected by performing Grubb’s test using an online GraphPad outlier calculator (http://graphpad.com/quickcalcs/
Grubbs1.cfm).
https://doi.org/10.1371/journal.pone.0191889.g003
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 7 / 13
(2017) also demonstrated the effect of RJ in reducing corticosterone levels in stressed rats [20].
Corticosterone synthesis is cholesterol-dependent, which indicates the possibility that RJ is
able to inhibit the synthesis of cholesterol. Major royal jelly protein 1 was identified as a hypo-
cholesterolemic protein [30], indicating a possible mechanism through which RJ could inhibit
corticosterone synthesis. Furthermore, the decreased corticosterone levels improved glucose
uptake [31], which could control glycemia even after stress induction.
Fontella et al. (2005) demonstrated that the repeated exposure of adult rats to restraint stress
causes a temporary suppression of food intake and reduction of body weight [32]. Herein, we
observed a decrease of body weight in both groups of stressed rats and non-stressed rats sup-
plemented with RJ, even without a diminution in food intake. These results corroborate a
prior study [32] demonstrating that the diminution of body weight in restriction and cold
stressed rats is attributable to an elevation of corticosterone levels. Furthermore, our data indi-
cate that the RJ can also diminish body weight even in the absence of stress induction.
Although we did not evaluate the mechanism by which supplementation with RJ reduces body
weight, other studies have also showed that RJ supplementation can diminish body weight [33,
34]. New studies must be conducted to investigate the mechanism by which this effect occurs.
Fig 4. Glutathione antioxidant defense system in liver tissue of rats stressed by immobilization and cold. Glutathione level (GSH) (A).
Glutathione peroxidase activity (GPx) (B). Glutathione reductase activity (GR) (C). Glucose-6-phosphate dehydrogenase activity (G6PDH) (D).
No stress (NS), No Stress supplemented with Royal Jelly (NSRJ), Stress (S) and Stress supplemented with Royal Jelly (SRJ). Values are expressed
as mean±SEM, p<0.05 vs. NS, # p <0.05 vs. S (One-way ANOVA followed by Tukey teste). Outliers were detected by performing Grubb’s
test using an online GraphPad outlier calculator (http://graphpad.com/quickcalcs/Grubbs1.cfm).
https://doi.org/10.1371/journal.pone.0191889.g004
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 8 / 13
Stress alters the availability of metabolic substrates and can influence blood glucose levels,
leading to an increase in oxidative stress [35]. Our results indicate that the glycemia of non-
stressed rats supplemented with royal jelly did not differ from the non-stressed group.
Although we did not measure the plasmatic insulin, a prior study demonstrated that RJ did
not affect insulin levels [36]. Thus, the augmentation of corticosterone levels is probably
responsible for increased the blood glucose level under this stress situation, due to its role in
hepatic gluconeogenesis [37]. Furthermore, a strong positive correlation between glycemia
and corticosterone levels was observed after the last stress induction session. These results
indicate not only that glycemic control is corticosterone-dependent in the stress response, but
also that after the last stress session (Sa and SRJa) the RJ supplementation diminished the
increase of blood glucose levels compared to Sa rats. Thus, the capacity to inhibit the increase
in blood glucose levels after stress induction indicates a potential anti-stress and adaptogenic
effects of RJ.
Corticosterone acts on the liver, increasing glucose production especially through gluco-
neogenesis [37]. It can also increase oxidative stress and induce damage in the liver tissue [38].
Stressed rats presented increased plasma GGT compared with NS rats, indicating hepatic dam-
age [39]. RJ supplementation reduced both GGT levels and AST compared with S rats, and
also reduced AST and ALP compared with NS rats. Other studies using models of toxicity
induced by lambda-cyhalothrin and azathioprine also found a decrease in these enzymes, sup-
porting the protective effect of RJ towards liver tissue [40,41]. Thus, data observed here sug-
gests a hepatoprotective effect of RJ, not only by improving the liver enzymes, but also the
antioxidative systems.
High levels of glucocorticoids and exposure to stress increase ROS [10,11]. Herein, stressed
rats had increased lipid peroxidation associated with the corticosterone level, corroborating
other studies [38,42]. However, RJ supplementation decreased the lipid peroxidation in the
liver of stressed rats. RJ peptides can diminish the peroxidation of linoleic acid and eliminate
hydroxyl radicals, inhibiting lipid peroxidation [43]. In addition, in the present study, stressed
rats decreased total antioxidant capacity associated with the increase of corticosterone levels,
whereas RJ supplementation restored FRAP to levels comparable to those of NS rats. RJ con-
tains vitamins B and E, zinc, copper [44], phenolic compounds [45] and peptides with antioxi-
dant actions [43]. These RJ compounds can act as antioxidant agents preventing the oxidative
damage in the liver, suggesting that RJ supplementation may improve the antioxidant defense
of stressed rats.
Furthermore, we analyzed the enzymatic and glutathione antioxidant defense system in the
liver tissues of the stressed rats. SOD activity decreased in stressed rats compared with NS and
increased in rats supplemented with RJ compared with S rats. Other studies have also shown a
decrease in this enzyme activity in the liver of rats undergoing stress, thereby corroborating
our results [46,47]. Oishi and Mashida (2009) reported a decrease in hepatic SOD mRNA six
hours after stress by immobilization and cold [48]. Furthermore, our findings of decreased
GSH and increased GR and G6PDH activities in stressed rats, indicate a compensatory mecha-
nism to maintain the redox cycle of GSH, as shown in other studies [11,42].
RJ supplementation also increased the GSH level, corroborating Karadeniz et al. (2011),
who showed that RJ-supplemented rats present increased GSH in the liver and kidney in an
oxidative stress model induced by cisplatin [49]. Furthermore, RJ supplementation decreased
GR activity compared to S rats, and increased GPx and G6PDH activities similar to NS rats.
Studies employing models of toxicity for cisplatin [49] and paracetamol [50] also showed
increased GPx activity in rat livers. The unchanged GPx activity between stressed rats shown
in the present study was not found in previous studies. Our finding may be attributable to the
stress model used in this study. To the best of our knowledge, this is the first study that has
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 9 / 13
observed the effect of RJ supplementation on the activity of GR and G6PDH in the liver during
a stress situation. The RJ antioxidant property may be derived from the short-chain peptides
[43], phenolic compounds (flavonoids and cinnamic acid derivatives) [45], some antioxidant
type vitamins (A and E) and fatty acids (trans-10-Hydroxy-2-decenoic) [19]. Therefore, these
results support the antioxidant activity of RJ and indicate a prevention of hepatic oxidative
damage caused by stress.
Conclusion
RJ decreases corticosterone and improves glycemia control after stress induction. Moreover,
RJ showed a hepatoprotective effect against oxidative damage, reducing lipoperoxidation and
increasing the total antioxidant capacity in liver tissues of restraint and cold stressed rats.
Taken together, these results highlight an adaptogenic role of RJ in situations of stress and oxi-
dative damage.
Acknowledgments
The authors gratefully acknowledge the Apia
´rio Girassol Ltda. (Uberla
ˆndia, Brazil) for donat-
ing the royal jelly for the development of this study; Center of Animal Experimentation
(CBEA-UFU) of the Federal University of Uberla
ˆndia for supplying the animals and infra-
structural support; Foundation of Support Research of the State of Minas Gerais (FAPEMIG)
for financial support; Laboratory of Clinical Analyses, School of Veterinary Medicine, Federal
University of Uberla
ˆndia for help with the plasma biochemical analysis, Laboratory of Broma-
tology and Animal Nutrition of the Federal University of Uberla
ˆndia for centesimal analysis of
the royal jelly and the support from the National Institute of Science and Technology in Thera-
nostics and Nanobiotechnology (INCT). DCC, HLM, AVS and DDV received graduate fellow-
ships from the National Council for Scientific and Technological Development (CNPq) and
Coordination for the Improvement of Higher Education Personnel (CAPES). LGP received
postdoctoral fellowships from the National Postdoctoral Program PNPD/CAPES and FSE is
recipient of grant from CNPq (308965/2015-9).
Author Contributions
Conceptualization: Renata Roland Teixeira, Helen Lara Machado, Foued Salmen Espindola.
Formal analysis: Douglas Carvalho Caixeta, Renata Roland Teixeira, Leonardo Gomes
Peixoto.
Funding acquisition: Foued Salmen Espindola.
Investigation: Douglas Carvalho Caixeta, Renata Roland Teixeira, Nathalia Belele Baptista,
Adriele Vieira de Souza, Danielle Diniz Vilela, Celso Rodrigues Franci.
Methodology: Renata Roland Teixeira, Helen Lara Machado, Foued Salmen Espindola.
Project administration: Renata Roland Teixeira, Helen Lara Machado.
Writing – original draft: Douglas Carvalho Caixeta, Renata Roland Teixeira, Leonardo
Gomes Peixoto.
Writing – review & editing: Douglas Carvalho Caixeta, Renata Roland Teixeira, Leonardo
Gomes Peixoto, Foued Salmen Espindola.
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 10 / 13
References
1. Budni J, Zomkowski AD, Engel D, Santos DB, dos Santos AA, Moretti M, et al. Folic acid prevents
depressive-like behavior and hippocampal antioxidant imbalance induced by restraint stress in mice.
Experimental neurology. 2013; 240:112–21. Epub 2012/11/13. https://doi.org/10.1016/j.expneurol.
2012.10.024 PMID: 23142187.
2. Klenerova
´V, Jurcovicova
´J, Kaminsky
´O, Sı
´da P, Krejcı
´I, Hlina
´k Z, et al. Combined restraint and cold
stress in rats: effects on memory processing in passive avoidance task and on plasma levels of ACTH
and corticosterone. Behav Brain Res. 2003; 142(1–2):143–9. PMID: 12798275.
3. Djordjevic J, Cvijic G, Davidovic V. Different activation of ACTH and corticosterone release in response
to various stressors in rats. Physiol Res. 2003; 52(1):67–72. Epub 2003/03/11. PMID: 12625809.
4. Solin AV, Lyashev YD. Stress-induced changes in the liver of rats with different resistance to stress.
Bull Exp Biol Med. 2014; 157(5):571–3. https://doi.org/10.1007/s10517-014-2617-7 PMID: 25257415.
5. Agrawal A, Jaggi AS, Singh N. Pharmacological investigations on adaptation in rats subjected to cold
water immersion stress. Physiol Behav. 2011; 103(3–4):321–9. https://doi.org/10.1016/j.physbeh.2011.
02.014 PMID: 21324329.
6. Bali A, Singh N, Jaggi AS. Investigations into mild electric foot shock stress-induced cognitive enhance-
ment: possible role of angiotensin neuropeptides. Journal of the renin-angiotensin-aldosterone system:
JRAAS. 2013; 14(3):197–203. Epub 2012/09/01. https://doi.org/10.1177/1470320312456579 PMID:
22936039.
7. Sierra M. Depersonalization disorder: pharmacological approaches. Expert review of neurotherapeu-
tics. 2008; 8(1):19–26. Epub 2007/12/20. https://doi.org/10.1586/14737175.8.1.19 PMID: 18088198.
8. Mlekusch W, Paletta B, Truppe W, Paschke E, Grimus R. Plasma concentrations of glucose, corticoste-
rone, glucagon and insulin and liver content of metabolic substrates and enzymes during starvation and
additional hypoxia in the rat. Horm Metab Res. 1981; 13(11):612–4. Epub 1981/11/01. https://doi.org/
10.1055/s-2007-1019352 PMID: 7030899.
9. Spiers JG, Chen HJ, Cuffe JS, Sernia C, Lavidis NA. Acute restraint stress induces rapid changes in
central redox status and protective antioxidant genes in rats. Psychoneuroendocrinology. 2016;
67:104–12. https://doi.org/10.1016/j.psyneuen.2016.02.005 PMID: 26881836.
10. Fontella FU, Siqueira IR, Vasconcellos AP, Tabajara AS, Netto CA, Dalmaz C. Repeated restraint
stress induces oxidative damage in rat hippocampus. Neurochem Res. 2005; 30(1):105–11. PMID:
15756938.
11. Sahin E, Gu¨mu¨şlu¨S. Cold-stress-induced modulation of antioxidant defence: role of stressedconditions
in tissue injury followed by protein oxidation and lipid peroxidation. Int J Biometeorol. 2004; 48(4):165–
71. https://doi.org/10.1007/s00484-004-0205-7 PMID: 15029490.
12. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense.
World Allergy Organ J. 2012; 5(1):9–19. Epub 2012/01/13. https://doi.org/10.1097/WOX.
0b013e3182439613 PMID: 23268465.
13. Brekhman II, Dardymov IV. New substances of plant origin which increase nonspecific resistance.
Annu Rev Pharmacol. 1969; 9:419–30. Epub 1969/01/01. https://doi.org/10.1146/annurev.pa.09.
040169.002223 PMID: 4892434.
14. Fujii A, Kobayashi S, Kuboyama N, Furukawa Y, Kaneko Y, Ishihama S, et al. Augmentation of wound
healing by royal jelly (RJ) in streptozotocin-diabetic rats. Japanese journal of pharmacology. 1990;53
(3):331–7. Epub 1990/07/01. PMID: 2391765.
15. Tokunaga KH, Yoshida C, Suzuki KM, Maruyama H, Futamura Y, Araki Y, et al. Antihypertensive effect
of peptides from royal jelly in spontaneously hypertensive rats. Biological & pharmaceutical bulletin.
2004; 27(2):189–92. Epub 2004/02/06. PMID: 14758031.
16. Chan QW, Melathopoulos AP, Pernal SF, Foster LJ. The innate immune and systemic response in
honey bees to a bacterial pathogen, Paenibacillus larvae. BMC genomics. 2009; 10:387. Epub 2009/
08/22. https://doi.org/10.1186/1471-2164-10-387 PMID: 19695106.
17. Okamoto I, Taniguchi Y, Kunikata T, Kohno K, Iwaki K, Ikeda M, et al. Major royal jelly protein 3 modu-
lates immune responses in vitro and in vivo. Life sciences. 2003; 73(16):2029–45. Epub 2003/08/06.
PMID: 12899927.
18. Kamakura M, Moriyama T, Sakaki T. Changes in hepatic gene expression associated with the hypocho-
lesterolaemic activity of royal jelly. The Journal of pharmacy and pharmacology. 2006; 58(12):1683–9.
Epub 2007/03/03. https://doi.org/10.1211/jpp.58.12.0017 PMID: 17331334.
19. Nagai T, Inoue R, Suzuki N, Nagashima T. Antioxidant properties of enzymatic hydrolysates from royal
jelly. Journal of medicinal food. 2006; 9(3):363–7. Epub 2006/09/29. https://doi.org/10.1089/jmf.2006.9.
363 PMID: 17004899.
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 11 / 13
20. Teixeira RR, de Souza AV, Peixoto LG, Machado HL, Caixeta DC, Vilela DD, et al. Royal jelly
decreases corticosterone levels and improves the brain antioxidant system in restraint and cold
stressed rats. Neuroscience letters. 2017; 655:179–85. Epub 2017/07/16. https://doi.org/10.1016/j.
neulet.2017.07.010 PMID: 28709905.
21. Paula-Freire LI, Mendes FR, Molska GR, Duarte-Almeida JM, Carlini EA. Comparison of the chemical
composition and biological effects of the roots, branches and leaves of Heteropterys tomentosa A.
Juss. Journal of ethnopharmacology. 2013; 145(2):647–52. Epub 2012/12/15. https://doi.org/10.1016/j.
jep.2012.12.004 PMID: 23237933.
22. Arnold M, Langhans W. Effects of anesthesia and blood sampling techniques on plasma metabolites
and corticosterone in the rat. Physiol Behav. 2010; 99(5):592–8. Epub 2010/02/10. https://doi.org/10.
1016/j.physbeh.2010.01.021 PMID: 20152845.
23. Reis FM, Albrechet-Souza L, Franci CR, Brandao ML. Risk assessment behaviors associated with cor-
ticosterone trigger the defense reaction to social isolation in rats: role of the anterior cingulate cortex.
Stress. 2012; 15(3):318–28. Epub 2011/10/14. https://doi.org/10.3109/10253890.2011.623740 PMID:
21992055.
24. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utiliz-
ing the principle of protein-dye binding. Analytical biochemistry. 1976; 72:248–54. Epub 1976/05/07.
PMID: 942051.
25. Diniz Vilela D, Gomes Peixoto L, Teixeira RR, Belele Baptista N, Carvalho Caixeta D, Vieira de Souza
A, et al. The Role of Metformin in Controlling Oxidative Stress in Muscle of Diabetic Rats. Oxid Med Cell
Longev. 2016; 2016:6978625. https://doi.org/10.1155/2016/6978625 PMID: 27579154.
26. Jafari M, Salehi M, Zardooz H, Rostamkhani F. Response of liver antioxidant defense system to acute
and chronic physical and psychological stresses in male rats. EXCLI journal. 2014; 13:161–71. Epub
2014/01/01. PMID: 26417250.
27. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, et al. The Role of Oxidative Stress and Antioxidants
in Liver Diseases. Int J Mol Sci. 2015; 16(11):26087–124. Epub 2015/11/02. https://doi.org/10.3390/
ijms161125942 PMID: 26540040.
28. Zafir A, Banu N. Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress
in rats. Stress. 2009; 12(2):167–77. https://doi.org/10.1080/10253890802234168 PMID: 18850490.
29. Celikbilek A, Gocmen AY, Tanik N, Yaras N, Yargicoglu P, Gumuslu S. Serum lipid peroxidation mark-
ers are correlated with those in brain samples in different stress models. Acta Neuropsychiatr. 2014; 26
(1):51–7. https://doi.org/10.1017/neu.2013.32 PMID: 25142100.
30. Kashima Y, Kanematsu S, Asai S, Kusada M, Watanabe S, Kawashima T, et al. Identification of a novel
hypocholesterolemic protein, major royal jelly protein 1, derived from royal jelly. PLoS One. 2014; 9(8):
e105073. https://doi.org/10.1371/journal.pone.0105073 PMID: 25144734.
31. Piato AL, Detanico BC, Linck VM, Herrmann AP, Nunes DS, Elisabetsky E. Anti-stress effects of the
"tonic"Ptychopetalum olacoides (Marapuama) in mice. Phytomedicine. 2010; 17(3–4):248–53. Epub
2009/08/18. https://doi.org/10.1016/j.phymed.2009.07.001 PMID: 19682881.
32. Harris RB, Zhou J, Youngblood BD, Rybkin II, Smagin GN, Ryan DH. Effect of repeated stress on body
weight and body composition of rats fed low- and high-fat diets. Am J Physiol. 1998; 275(6 Pt 2):
R1928–38. PMID: 9843882.
33. Guo H, Saiga A, Sato M, Miyazawa I, Shibata M, Takahata Y, et al. Royal jelly supplementation
improves lipoprotein metabolism in humans. J Nutr Sci Vitaminol (Tokyo). 2007; 53(4):345–8. PMID:
17934240.
34. Pourmoradian S, Mahdavi R, Mobasseri M, Faramarzi E. Effects of royal jelly supplementation on body
weight and dietary intake in type 2 diabetic females. Health Promot Perspect. 2012; 2(2):231–5. https://
doi.org/10.5681/hpp.2012.028 PMID: 24688939.
35. Chang CM, Hsieh CJ, Huang JC, Huang IC. Acute and chronic fluctuations in blood glucose levels can
increase oxidative stress in type 2 diabetes mellitus. Acta Diabetol. 2012; 49 Suppl 1:S171–7. https://
doi.org/10.1007/s00592-012-0398-x PMID: 22547264.
36. Ghanbari E, Nejati V, Khazaei M. Improvement in Serum Biochemical Alterations and Oxidative Stress
of Liver and Pancreas following Use of Royal Jelly in Streptozotocin-Induced Diabetic Rats. Cell journal.
2016; 18(3):362–70. Epub 2016/09/08. https://doi.org/10.22074/cellj.2016.4564 PMID: 27602318.
37. Nirupama R, Devaki M, Yajurvedi HN. Chronic stress and carbohydrate metabolism: persistent changes
and slow return to normalcy in male albino rats. Stress. 2012; 15(3):262–71. https://doi.org/10.3109/
10253890.2011.619604 PMID: 21992064.
38. Sahin E, Gu¨mu¨şlu¨S. Stress-dependent induction of protein oxidation, lipid peroxidation and anti-oxi-
dants in peripheral tissues of rats: comparison of three stress models (immobilization, cold and immobi-
lization-cold). Clin Exp Pharmacol Physiol. 2007; 34(5–6):425–31. https://doi.org/10.1111/j.1440-1681.
2007.04584.x PMID: 17439411.
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 12 / 13
39. Yang Y, Wang H, Guo Y, Lei W, Wang J, Hu X, et al. Metal Ion Imbalance-Related Oxidative Stress Is
Involved in the Mechanisms of Liver Injury in a Rat Model of Chronic Aluminum Exposure. Biol Trace
Elem Res. 2016. https://doi.org/10.1007/s12011-016-0627-1 PMID: 26811106.
40. Cavusoglu K, Yapar K, Oruc E, Yalcin E. The protective effect of royal jelly on chronic lambda-cyhalo-
thrin toxicity: serum biochemical parameters, lipid peroxidation, and genotoxic and histopathological
alterations in swiss albino mice. Journal of medicinal food. 2011; 14(10):1229–37. Epub 2011/06/15.
https://doi.org/10.1089/jmf.2010.0219 PMID: 21663479.
41. Cemek M, Aymelek F, Buyukokuroglu ME, Karaca T, Buyukben A, Yilmaz F. Protective potential of
Royal Jelly against carbon tetrachloride induced-toxicity and changes in the serum sialic acid levels.
Food Chem Toxicol. 2010; 48(10):2827–32. Epub 2010/07/20. https://doi.org/10.1016/j.fct.2010.07.013
PMID: 20637822.
42. Hidalgo J, Gasull T, Garcia A, Blanquez A, Armario A. Role of glucocorticoids and catecholamines on
hepatic thiobarbituric acid reactants in basal and stress conditions in the rat. Horm Metab Res. 1991;
23(3):104–9. https://doi.org/10.1055/s-2007-1003626 PMID: 1650747.
43. Guo H, Ekusa A, Iwai K, Yonekura M, Takahata Y, Morimatsu F. Royal jelly peptides inhibit lipid peroxi-
dation in vitro and in vivo. J Nutr Sci Vitaminol (Tokyo). 2008; 54(3):191–5. PMID: 18635904.
44. Karaali A, Meydanoǧlu F, Eke D. Studies on Composition, Freeze-Drying and Storage of Turkish Royal
Jelly. 2015.
45. Kolayli S, Sahin H, Can Z, Yildiz O, Malkoc M, Asadov A. A Member of Complementary Medicinal Food:
Anatolian Royal Jellies, Their Chemical Compositions, and Antioxidant Properties. J Evid Based Com-
plementary Altern Med. 2015. https://doi.org/10.1177/2156587215618832 PMID: 26620573.
46. Su D, Zhang R, Zhang C, Huang F, Xiao J, Deng Y, et al. Phenolic-rich lychee (Litchi chinensis Sonn.)
pulp extracts offer hepatoprotection against restraint stress-induced liver injury in mice by modulating
mitochondrial dysfunction. Food Funct. 2016; 7(1):508–15. https://doi.org/10.1039/c5fo00975h PMID:
26569420.
47. Samarghandian S, Farkhondeh T, Samini F, Borji A. Protective Effects of Carvacrol against Oxidative
Stress Induced by Chronic Stress in Rat’s Brain, Liver, and Kidney. Biochem Res Int. 2016;
2016:2645237. https://doi.org/10.1155/2016/2645237 PMID: 26904286.
48. Oishi K, Machida K. Different effects of immobilization stress on the mRNA expression of antioxidant
enzymes in rat peripheral organs. http://dx.doi.org/10.1080/003655102753611735. 2009.
49. Karadeniz A, Simsek N, Karakus E, Yildirim S, Kara A, Can I, et al. Royal jelly modulates oxidative
stress and apoptosis in liver and kidneys of rats treated with cisplatin. Oxid Med Cell Longev. 2011;
2011:981793. Epub 2011/09/10. https://doi.org/10.1155/2011/981793 PMID: 21904651.
50. Kanbur M, Eraslan G, Beyaz L, Silici S, Liman BC, Altinordulu S, et al. The effects of royal jelly on liver
damage induced by paracetamol in mice. Exp Toxicol Pathol. 2009; 61(2):123–32. https://doi.org/10.
1016/j.etp.2008.06.003 PMID: 18693095.
Royal jelly in chronic stress
PLOS ONE | https://doi.org/10.1371/journal.pone.0191889 January 29, 2018 13 / 13
... They report the requirement for further studies in order to identify certain action mechanisms. Caixeta et al. (2018) [150] carried out a study assessing natural products with hepatoprotective activity. Liver tissues are vulnerable to acute and chronic stress; thus, the authors aimed to improve the organism's capacity to adapt to different stress conditions. ...
... They report the requirement for further studies in order to identify certain action mechanisms. Caixeta et al. (2018) [150] carried out a study assessing natural products with hepatoprotective activity. Liver tissues are vulnerable to acute and chronic stress; thus, the authors aimed to improve the organism's capacity to adapt to different stress conditions. ...
Article
Full-text available
Royal jelly (RJ) is one of the most valued natural products and is known for its health-promoting properties. Due to its therapeutic effects, it has been used in medicine since antiquity. Nowadays, several studies indicate that RJ acts as a powerful antimicrobial agent. Indeed, researchers shed light on its antioxidant and anticancer activity. RJ’s biological properties are related to its bioactive compounds, such as proteins, peptides, phenolic, and fatty acids. The aim of this review is to highlight recent findings on RJ’s main bioactive compounds correlated with its health-promoting properties. The available literature suggests that these bioactive compounds can be used as an alternative approach in order to enhance human health. Moreover, throughout this paper, we underline the prominent antibacterial effect of RJ against several target bacterial strains. In addition, we briefly discuss other therapeutic activities, such as antioxidative and anticancer effects, of this outstanding natural product.
... They report the requirement for further studies in order to identify certain action mechanisms. Caixeta et al. (2018) [150] carried out a study assessing natural products with hepatoprotective activity. Liver tissues are vulnerable to acute and chronic stress; thus, the authors aimed to improve the organism's capacity to adapt to different stress conditions. ...
... They report the requirement for further studies in order to identify certain action mechanisms. Caixeta et al. (2018) [150] carried out a study assessing natural products with hepatoprotective activity. Liver tissues are vulnerable to acute and chronic stress; thus, the authors aimed to improve the organism's capacity to adapt to different stress conditions. ...
... To measure GPx activity, the plasma was incubated with GPx buffer (100 mM potassium phosphate containing 1 mM EDTA, pH 7.7), sodium azide (40 mM), GSH (diluted in 5% metaphosphoric acid), GR (diluted in GPx buffer), NADPH (diluted with 5% sodium bicarbonate) and tert-butyl hydroperoxide (0.5 mM). The reduction in NADPH concentration was evaluated for 10 min in a spectrophotometer at 340 nm [39]; • Total antioxidant capacity due to ferric-reducing antioxidant power (FRAP) was determined by the ability of antioxidants present in blood samples to reduce Fe 3+ to Fe 2+ which is chelated by TPTZ (2,4,6-tris(2-pyridyl)-s-triazine) and forms the Fe 2+ TPTZ complex. This complex was quantified in a spectrophotometer at 593 nm, and antioxidant activity was determined by means of an analytical curve, constructed with trolox as the standard [40]; ...
Article
Full-text available
Postmenopausal women have a high prevalence of cardiometabolic diseases and that may associate with higher oxidative stress. Exercise can contribute to the treatment of such diseases, but some modalities, such as Mat Pilates, need to be further studied in terms of their physiological responses. Our aim was to investigate the effects of 12 weeks of Mat Pilates on redox status in postmenopausal women with one or multiple comorbidities of cardiometabolic diseases. Forty-four postmenopausal women were divided into two groups: SINGLE, composed of women with one cardiometabolic disease (n = 20) and MULT, with multimorbidity (n = 24). Mat Pilates training was conducted three times a week for 12 weeks, and each session lasted 50 min. Plasma samples were collected before and after training to analyze the following redox markers: superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity due to ferric-reducing antioxidant power (FRAP), reduced glutathione (GSH), uric acid, and carbonyl protein. ANCOVA showed interaction effects in FRAP (p = 0.014). Both groups had reduced levels of catalase (p = 0.240) and GSH (p = 0.309), and increased levels of carbonyl protein (p = 0.053) after intervention. In conclusion, the redox status of postmenopausal women shows no changes mediated by Mat Pilates training between SINGLE and MULT, except for greater reductions of FRAP in SINGLE.
... The use of in vivo models [26,27] in laboratory rodents makes it possible to reproduce various stress scenarios, such as hypothermia [28], increased physical activity [29], and emotional stress [30]. Laboratory animals, unlike humans, are characterized by instinctive behavior under a particular model, which is an advantage in preclinical testing on adaptogenic properties and permits the exclusion of many factors related to the heterogeneity of stress conditions in humans. ...
Article
Full-text available
Increasing the ability of the human body to adapt in conditions of physical or emotional stress is promising from the standpoint of the use of preventive nutrition containing functional food ingredients (FFI) with proven effectiveness in complex physiological in vivo studies. In this work, we developed FFI from spinach leaves (Spinacia oleracea L.) with a high content of polyphenols and adaptogens—phytoecdysteroids. Using in vivo models of increased physical activity and immobilization-induced emotional stress, we evaluated the nonspecific resistance of rats in response to the addition of the developed FFI to the diet. In the acute toxicity experiment, we found no signs of FFI toxicity up to 5000 mg/kg body weight. As a result of the daily 26-day consumption of FFI, we observed an anxiolytic effect in physiological studies. FFI prevented an increase in the content of biogenic amines in the blood, the main markers of the stress system, and had a positive effect on the lipid metabolism of the rats. The obtained results demonstrate a “smoothing” effect on the body’s reaction in response to induced stress conditions.
... Accumulating evidence suggests that cold stress is the most common source of environmental stress and can damage the nervous, cardiovascular and immune systems. 45,46 The liver is an important heat-generating organ in the body, which is responsible for heat production during acute cold stimulation to maintain core body temperature. 47 Cold-stress-induced liver injury significantly increases serum ALT and AST levels and liver histopathological changes. ...
Article
Full-text available
Procyanidin B2 (PB2), a naturally occurring flavonoid abundant in a wide range of fruits, has been shown to exert antioxidant, anti-inflammatory and anticancer properties. However, the role of PB2 in the prevention of cold stimulation (CS)-induced liver injury. The present study was undertaken to determine the effects of PB2 on liver injury induced by cold stimulation and its potential molecular mechanisms. The present study results showed that treatment with PB2 significantly reduced CS-induced liver injury by alleviating histopathological changes and serum levels of alanine transaminase and aspartate transaminase. Moreover, treatment with PB2 inhibited secretion of inflammatory cytokines and oxidative stress in cold-stimulated mice. PB2 reduced cold stimulation-induced inflammation by inhibiting TLR4/NF-κB and Txnip/NLRP3 signalling. Treatment with PB2 reduced oxidative stress by activating Nrf-2/Keap1, AMPK/GSK3β signalling pathways and autophagy. Furthermore, simultaneous application of Shh pathway inhibitor cyclopamine proved that PB2 targets the Hh pathway. More importantly, co-treatment with PB2 and cyclopamine showed better efficacy than monotherapy. In conclusion, our findings provide new evidence that PB2 has protective potential against CS-induced liver injury, which might be closely linked to the inhibition of Shh signalling pathway.
... The best of our knowledge, cold-restraint stress (CRS) induced hepatic dysfunction in rats [29][30]. Liver damage cause damage to the stability and integrity of various bio lms and increase their permeability, leading to the out ow of enzymes in the cytoplasm into the blood, such as ALT and AST. ...
Preprint
Full-text available
Objectives: In order to research the erucamide effect on Stress-induced rats liver injury and potential mechanism of the protect effect. Methods: Stress-induced liver injury in SD rats was used as an in vivo model. Adult female SD rats were differentiated into three groups: Normal group, SLI(Stress-induced liver injury)-group and [SLI+Erucamide (95.4uM/Kg)]-treated group. In addition, the transcriptomes from 9 liver tissues were sequenced using an Illumina sequencing platform, screened the differentially expressed genes and related cell signal transduction pathways. Gene expression was measured by RT-qPCR. Furthermore, observe the pathological changes of rats liver tissues by HE staining , and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by microplate method. Human LO2 cells was used for in vitro model, the cells in the logarithmic growth phase were differentiated into normal group, corticosterone groups, erucamide, and glycine intervention groups. Corticosterone (300uM) was used to induce LO2 cell damage in vitro. And using tetrazolium (MTT) colorimetric method to determine and calculate cells viability. Hoechst 33342 staining was used to observe the morphology of hepatocyte apoptosis. Result: This study showed that erucamide has a significant effect on Stress-induced liver injury in rats, which is proved by HE staining test and ALT / AST detection experiment (p<0.05). The results of transcriptomes indicated that erucamide could inhibit the cleavage of glycine to prevent stress-induced liver injury in rats. Moreover, RT-qPCR results demonstrated that erucamide reduced the expression of DLD and AMT(p<0.05) genes in glycine cleavage system, thereby reducing glycine cleavage. Compared with the SLI group, erucamide inhibited UNC5B gene expression(p<0.05), which is related to cell apoptosis, indicating that erucamide can inhibit cell apoptosis. In addition, erucamide inhibited the expression of GPSM3 (p<0.05) and IGSF11 that are associated with inflammation. In addition, both erucamide and glycine could prevent the damage of LO2 hepatocytes induced by CORT. Erucamide and Glycine were effective in preventing Crot-induced LO2 cell damage. Conclusions: In this research, erucamide inhibits the cleavage of glycine to anti-stress liver injury in rats.
Article
The indiscriminate use of pesticides has led to an increased risk of environmental contamination and pest resistance worldwide, favoring the development of less hazardous formulations. The commercial insecticide ZEUS® (Ihara, Brazil) combining dinotefuran and lambda-cyhalothrin was recently formulated in order to meet the environmental sustainability and food security. However, little is known about the potential toxic effects of ZEUS® to aquatic species. Thus, we report, for the first time, the biochemical and histological responses in tilapia (Oreochromis niloticus) following 96 h exposure to 0.01 mg/L, 0.05 mg/L and 0.1 mg/L ZEUS®. Different biochemical endpoints, including acetylcholinesterase (AChE), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP), were assessed as potential biomarkers of insecticide effects. Glutathione S-transferase (GST) was evaluated as a marker of phase II biotransformation, and histopathological changes were measured to indicate gill alterations following ZEUS® exposure. After 96 h exposure, ZEUS® treatment increased GST activity in the liver of fish exposed to the highest concentration, while the intermediate dose increased both renal GGT and hepatic ALP activities. These findings reflect the importance of the liver and kidneys in the detoxification of ZEUS® and highlight the need to understand further toxicity effects. Likewise, the histopathological analysis of gills provided evidence that ZEUS® caused moderate damages. Despite biomarkers alterations reported for O. niloticus following ZEUS® exposure, by comparing our findings with data on toxicity of individual pesticides, the commercial ZEUS® mixture seems to present similar or even lower adverse effects on freshwater fish.
Article
Environmental pollution by metals has repercussions on wildlife health. It is known that some metals can have an influence on the neuroendocrine stress response, and at the same time, metals have pro-oxidant effects that can overwhelm the antioxidant system and cause oxidative stress. This study evaluates the association of metals with neuroendocrine stress activity and biomarkers of oxidative stress in 42 captive female Morelet's crocodiles (Crocodylus moreletii). We measured five metals of ecotoxicological importance (Hg, Cd, Pb, Cu and Zn), and three biomarkers of the oxidative stress response in the liver: glutathione (GSH) and glutathione disulfide (GSSG) as markers for antioxidant system and thiobarbituric acid reactive substances (TBARS) for oxidative damage. We also measured one biomarker of the neuroendocrine response to stress: corticosterone (B) in blood plasma. The mean ± SD concentrations of metals in the liver expressed in μg/g (dw) were: Cd: 0.004 ± 0.003, Hg: 0.014 ± 0.019, Cu: 0.017 ± 0.013, Zn: 0.043 ± 0.035, Pb: 0.16 ± 0.256. The mean ± SD of GSH was 0.42 ± 0.35 nmol/mg protein, the mean ± SD of GSSG was 0.24 ± 0.20 nmol/mg protein, the mean ± SD concentrations of TBARS were 0.36 ± 0.21 nmol/mg protein, and the mean ± SD of B was 393.57 ± 405.14 pg/mL. Hg presented a significant negative relationship with corticosterone. Cd had a negative relationship with both GSH and GSSG; meanwhile, Zn showed a negative relationship with TBARS levels, could be a protective element against hepatic oxidative damage. Finally, B had negative relationship with oxidative damage. The connection found between Hg and the neuroendocrine stress response, as well as the correlations of Cd and Zn with oxidative damage and antioxidant activity should be studied further, given their toxicological importance and implications for the conservation of C. moreletii and other crocodilians.
Article
Royal jelly (RJ) is a kind of bee product widely used in cosmetics, medicine and other fields. Not only can RJ regulate the physiological function of bee population, but also play a specific biological role in many diseases. This paper overviews the main active ingredients in the functional food RJ, including major royal jelly protein, fatty acids, phenols, flavonoids, etc, and summarizes the active role of RJ in the maintenance of human health, such as the regulation of immunity, lifespan, memory, digestive system, blood glucose, obesity, antibacterial and anti-cancer effect, among which the regulation of memory can be used in the treatment of Alzheimer's disease. These findings will benefit for comprehensive understanding and use of RJ, hence making it more effective in maintaining health.
Article
Full-text available
Testicular heat stress (HS) can lead to testicular tissue destruction and spermatogenesis disturbances. Royal Jelly (RJ) has been introduced as a potent antioxidant. We investigated the effects of RJ on testicular tissue, oxidative stress and sperm apoptosis in HS-exposed rats. Compared to HS-exposed groups, RJ co-treatment could improve testosterone reduction and histopathological damages. The RJ co-administration decreased MDA level in testicular tissue, while TAC and CAT levels were remarkably increased compared to HS-exposed groups. Moreover, significant higher expression level of Bcl-2 and lower expression levels of P53 and Caspase-3 were seen following RJ co-administration compared to HS-exposed groups. Our data suggest that RJ can effectively ameliorate experimental HS-induced testiculopathies in rats through testicular antioxidant defense system restoration and germ cells apoptosis regulation.
Article
Full-text available
Metformin can act in muscle, inhibiting the complex I of the electron transport chain and decreasing mitochondrial reactive oxygen species. Our hypothesis is that the inhibition of complex I can minimize damage oxidative in muscles of hypoinsulinemic rats. The present study investigated the effects of insulin and/or metformin treatment on oxidative stress levels in the gastrocnemius muscle of diabetic rats. Rats were rendered diabetic (D) with an injection of streptozotocin and were submitted to treatment with insulin (D+I), metformin (D+M), or insulin plus metformin (D+I+M) for 7 days. The body weight, glycemic control, and insulin resistance were evaluated. Then, oxidative stress levels, glutathione antioxidant defense system, and antioxidant status were analyzed in the gastrocnemius muscle of hypoinsulinemic rats. The body weight decreased in D+M compared to ND rats. D+I and D+I+M rats decreased the glycemia and D+I+M rats increased the insulin sensitivity compared to D rats. D+I+M reduced the oxidative stress levels and the activity of catalase and superoxide dismutase in skeletal muscle when compared to D+I rats. In conclusion, our results reveal that dual therapy with metformin and insulin promotes more benefits to oxidative stress control in muscle of hypoinsulinemic rats than insulinotherapy alone.
Article
Full-text available
Objective: This study aimed to evaluate the effects of royal jelly (RJ) on serum biochemical alterations and oxidative stress status in liver and pancreas of streptozotocin (STZ)- induced diabetic rats. Materials and methods: In this experimental study, thirty two male Wistar rats were divided into the following four groups (n=8/group): i. Control (C), ii. Diabetic (D), iii. Royal jelly (R), and iv. Royal jelly-treated diabetic (D/R) groups. Diabetes was induced by single intraperitoneal (IP) injection of STZ (60 mg/kg). The RJ [100 mg/kg body weight (BW)] was administered orally for 42 days. Blood samples were used to determine serum levels of insulin, high density lipoprotein cholesterol (HDL-c), total protein (TP), albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and fasting blood glucose (FBG). Also, the antioxidant status was evaluated by determining the levels of malondialdehyde (MDA), catalase (CAT) and ferric reducing antioxidant power (FRAP) in liver and pancreas. Data were analyzed by one-way analysis of variance (ANOVA) with P<0.05 as the significant level. Results: STZ-induced diabetic rats showed a significant elevation in the serum levels of AST, ALT, ALP and FBG, whereas there was a significant decrease in serum levels of insulin, albumin, HDL-c and TP (P<0.05). Treatment of the diabetic rats with RJ restored the changes of the above parameters to their normal levels (P<0.05). In addition, RJ significantly improved reduced levels of FRAP and CAT as well as high MDA level in liver and pancreas (P<0.05). Conclusion: RJ improves oxidative damage induced by STZ in the liver and pancreas of rats; therefore, it can be considered as an effective and alternative treatment for diabetes.
Article
Full-text available
The objective of the study is to investigate the effects of chronic aluminum overload on rat liver function and its induction of pathological changes in metal ion levels and oxidative stress in hepatic tissues. Wistar rats were intragastrically administered aluminum gluconate (200 mg Al3+/Kg) once a day, 5 days a week, for 20 weeks. HE staining was used to visualize pathological changes in rat liver tissue. A biochemical method was adopted to detect ALT, AST, ALP, and GGT levels, as well as liver SOD activity and blood plasma MDA content. A plasma atomic emission spectrophotometer was used to detect Al, Mn, Fe, Zn, and Cu ion contents in liver tissue. Our results showed obvious vacuolar degeneration, granular degeneration, and spotty necrosis in chronic Al-overload rat hepatocytes. The levels of ALT, AST, ALP, and GGT were significantly increased. Liver SOD activity was significantly decreased, and MDA content was significantly increased. In Al-overload rat liver, Al, Mn, Fe, and Cu contents were significantly increased, and in Al-overload rat serum, Mn, Fe, Zn, and Cu contents were significantly decreased. However, the Al level in Al-overload rat serum was not significantly different from that in control rat serum. These results suggest that chronic aluminum overload causes obvious damage to rat liver and causes imbalances in Al, Mn, Fe, Zn, and Cu levels in rat liver and serum. Metal ion imbalance-related oxidative stress may be involved in the mechanism of chronic liver injury caused by aluminum overload.
Article
Full-text available
Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR) has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher ( P < 0.001 ) and the levels of GSH and antioxidant enzymes were significantly lower than the nonstressed animals ( P < 0.001 ). CAR ameliorated the changes in the stressed animals as compared with the control group ( P < 0.001 ). This study indicates that CAR can prevent restraint stress induced oxidative damage.
Article
Full-text available
This study investigated various chemical and antioxidant properties of Anatolian royal jelly samples. Moisture, pH, total protein, 10-hydroxy-2-decenoic acid (10-HDA) and sugars were analyzed from 18 samples. Total phenolic contents, ferric reducing antioxidant capacity and 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging activity were measured as antioxidant determinants. 10-HDA contents and total protein content of fresh weight ranged between 1.0% and 3.9%, and 11.4% and 15.8%, respectively. The main sugars detected were glucose and fructose. Maltose, trehalose, and melibiose were detected at less than 1.0% in all samples. Lactose, a milk sugar, was detected in only 3 samples, at values between 0.8% and 1.4%. Total henolic content ranged from 91.0 to 301.0 mg gallic acid equivalents/kg fresh weight. Antioxidant activity is due to both to the total phenolic content, proteins and fatty acids of royal jelly. Anatolian royal jelly samples were not different from other royal jelly samples from across the world.
Article
Restraint and cold stress induces the hypothalamic-pituitary-adrenal (HPA) axis to release corticosterone from the adrenal gland, which can worsen the antioxidant defense system in the central nervous system. Here, we investigated the corticosterone levels and the antioxidant defense system in the cerebellum and brain, as well as in its isolated regions, such as cerebral cortex, striatum and hippocampus of stressed rats supplemented with royal jelly (RJ). Wistar rats were supplemented with RJ for 14 days and the stress induction started on the 7th day. Stressed rats increased corticosterone levels, glycemia and lipid peroxidation in the brain and cerebellum, cerebral cortex and hippocampus besides reduced glutathione defense system in the brain and striatum. Rats supplemented with RJ decreased corticosterone, maintained glycemia and decreased lipid peroxidation in the brain, cerebellum, as well as striatum and hippocampus, besides improved glutathione defense system in cerebral cortex and striatum. This study suggests an anti-stress and neuroprotective effect of RJ under stress conditions.
Article
Objective This study aimed to evaluate the effects of royal jelly (RJ) on serum biochemical alterations and oxidative stress status in liver and pancreas of streptozotocin (STZ)- induced diabetic rats. Materials and Methods In this experimental study, thirty two male Wistar rats were divided into the following four groups (n=8/group): i. Control (C), ii. Diabetic (D), iii. Royal jelly (R), and iv. Royal jelly-treated diabetic (D/R) groups. Diabetes was induced by single intraperitoneal (IP) injection of STZ (60 mg/kg). The RJ [100 mg/kg body weight (BW)] was administered orally for 42 days. Blood samples were used to determine serum levels of insulin, high density lipoprotein cholesterol (HDL-c), total protein (TP), albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and fasting blood glucose (FBG). Also, the antioxidant status was evaluated by determining the levels of malondialdehyde (MDA), catalase (CAT) and ferric reducing antioxidant power (FRAP) in liver and pancreas. Data were analyzed by one-way analysis of variance (ANOVA) with P<0.05 as the significant level. Results STZ-induced diabetic rats showed a significant elevation in the serum levels of AST, ALT, ALP and FBG, whereas there was a significant decrease in serum levels of insulin, albumin, HDL-c and TP (P<0.05). Treatment of the diabetic rats with RJ restored the changes of the above parameters to their normal levels (P<0.05). In addition, RJ significantly improved reduced levels of FRAP and CAT as well as high MDA level in liver and pancreas (P<0.05). Conclusion RJ improves oxidative damage induced by STZ in the liver and pancreas of rats; therefore, it can be considered as an effective and alternative treatment for diabetes.
Article
The stress-induced imbalance in reduction/oxidation (redox) state has been proposed to play a major role in the etiology of neurological disorders. However, the relationship between psychological stress, central redox state, and potential protective mechanisms within specific neural regions has not been well characterized. In this study, we have used an acute psychological stress to demonstrate the dynamic changes that occur in the redox system of hippocampal and striatal tissue. Outbred male Wistar rats were subject to 0 (control), 60, 120, or 240 minutes of acute restraint stress and the hippocampus and striatum were cryodissected for redox assays and relative gene expression. Restraint stress significantly elevated oxidative status and lipid peroxidation, while decreasing glutathione ratios overall indicative of oxidative stress in both neural regions. These biochemical changes were prevented by prior administration of the glucocorticoid receptor antagonist, RU-486. The hippocampus also demonstrated increased glutathione peroxidase 1 and 4 antioxidant expression which was not observed in the striatum, while both regions displayed robust upregulation of the antioxidant, metallothionein 1a. This was observed with concurrent upregulation of 11β-hydroxysteroid dehydrogenase 1, a local reactivator of corticosterone, in addition to decreased expression of the cytosolic regulatory subunit of superoxide-producing enzyme, NADPH-oxidase. Together, this study demonstrates distinctive regional redox profiles following acute stress exposure, in addition to identifying differential capabilities in managing oxidative challenges via altered antioxidant gene expression in the hippocampus and striatum.