close

Вход

Забыли?

вход по аккаунту

?

00015458.2017.1394672

код для вставкиСкачать
Acta Chirurgica Belgica
ISSN: 0001-5458 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/tacb20
Protective effects of gallic acid against
methotrexate-induced toxicity in rats
Farzin Safaei, Saeed Mehrzadi, Hossein Khadem Haghighian, Azam
Hosseinzadeh, Ali Nesari, Mojtaba Dolatshahi, Mahdi Esmaeilizadeh &
Mehdi Goudarzi
To cite this article: Farzin Safaei, Saeed Mehrzadi, Hossein Khadem Haghighian, Azam
Hosseinzadeh, Ali Nesari, Mojtaba Dolatshahi, Mahdi Esmaeilizadeh & Mehdi Goudarzi (2017):
Protective effects of gallic acid against methotrexate-induced toxicity in rats, Acta Chirurgica
Belgica, DOI: 10.1080/00015458.2017.1394672
To link to this article: http://dx.doi.org/10.1080/00015458.2017.1394672
Published online: 25 Oct 2017.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=tacb20
Download by: [University of Florida]
Date: 27 October 2017, At: 02:49
ACTA CHIRURGICA BELGICA, 2017
https://doi.org/10.1080/00015458.2017.1394672
ORIGINAL PAPER
Protective effects of gallic acid against methotrexate-induced toxicity
in rats
Farzin Safaeia, Saeed Mehrzadib , Hossein Khadem Haghighianc, Azam Hosseinzadehb, Ali Nesarid,
Mojtaba Dolatshahie , Mahdi Esmaeilizadehf and Mehdi Goudarzig
Downloaded by [University of Florida] at 02:49 27 October 2017
a
Health Promotion Research Center, Iran University of Medical Sciences, Tehran, Iran; bRazi Drug Research Center, Iran University
of Medical Sciences, Tehran, Iran; cDepartment of Nutrition, Faculty of Health, Qazvin University of Medical Sciences, Qazvin, Iran;
d
Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; eDepartment of
Physiology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran; fStudent Research Committee, Esfarayen
Faculty of Medical Sciences, Esfarayen, Iran; gDepartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran
ABSTRACT
ARTICLE HISTORY
Background: Methotrexate, as a chemotherapy drug, can cause chronic liver damage and
oxidative stress. Aim of this study was to evaluate the preventive effect of gallic acid (GA) on
methotrexate (MTX)-induced oxidative stress in rat liver.
Methods: Twenty-eight male rats were randomly divided into four groups as control, MTX
(20 mg/kg, i.p.), MTX þ GA (30 mg/kg/day, orally) and GA treated. Aspartate aminotransferase
(AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. Malondialdehyde (MDA) and glutathione (GSH)
levels and hepatic antioxidant enzymes activities including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed in liver tissue. The expression of
SOD2 and GPx1 genes were evaluated by real-time RT-PCR and liver histopathology was
evaluated by light microscopy.
Results: The result obtained from current study showed that GA remarkably reduced MTXinduced elevation of AST, ALT and ALP and increased MTX-induced reduction in GSH content, GPx, CAT and SOD activity as well as GPx1 and SOD2 gene expressions. Histological
results showed that MTX led to liver damage and GA could improve histological changes.
Conclusions: Our results indicate that GA ameliorates biochemical and oxidative stress
parameters in the liver of rats exposed to MTX.
Received 22 August 2017
Accepted 9 October 2017
1. Introduction
Methotrexate (MTX), 4-amino, 10-methyl analog of
folate, is an antimetabolite preventing DNA synthesis and cell proliferation via inhibition of dihydrofolate reductase (DHFR), converting dihydrofolate to
tetrahydrofolate [1]. Due to efficacy and long track
record of safety, MTX is mainly used as a mainstay
of in the therapy of rheumatoid arthritis, psoriasis,
malignant tumors and non-neoplastic diseases [2].
In cells and tissues, MTX has been shown to be
converted to MTX-polyglutamates (MTX-glu), which
is responsible for the most biochemical activities of
MTX [3]. The most common minor adverse effects
reported with low-dose MTX usage include headaches, anorexia, fatigue, stomatitis and nausea [4].
These side effects probably occur due to the inhibition of dihydrofolate reductase, required for preserving the integrity of cellular tetrahydrofolate
pool during purine and thymidine nucleotides
CONTACT Mehdi Goudarzi
Sciences, Ahvaz, Iran
Goudarzi787@gmail.com
ß 2017 The Royal Belgian Society for Surgery
KEYWORDS
Methotrexate; oxidative
stress; gallic acid; rat
synthesis [5]. The most serious side effect of MTX
includes hepatotoxicity. Although the exact mechanism of MTX-induced hepatic damage is not fully
understood, experimental and clinical evidence
have revealed that the oxidative stress may be the
main cause of MTX-induced side effects [6,7].
Methotrexate has been shown to exert anticancer,
anti-inflammatory, immunosuppressive and apoptotic effects via inducing the production of reactive
oxygen species (ROS) in both normal and cancer
cells [8]. Furthermore, MTX inhibits cytosolic NAD
(P)-dependent dehydrogenase and NADP malic
enzyme leading to the reduction of NADPH availability in cells, which in normal conditions acts an
electron donor for regenerating free radical scavengers such as glutathione [9,10]. Therefore, MTX
results in the failure of antioxidant defence system
leading to increased sensitivity of cells to ROSmediated injury [11].
Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical
Downloaded by [University of Florida] at 02:49 27 October 2017
2
F. SAFAEI ET AL.
Mammalian cells have been equipped with
complicated
systems
of
defence
against
ROS-mediated injury, including enzymic and nonenzymic antioxidant such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase
(SOD) and glutathione. Furthermore, phytochemicals of plant origin with inherent antioxidant
properties could protect oxidative stress induced
damage in the cells via scavenging free radicals
as well as boosting cellular antioxidant capacity
[12]. In recent years, animal and clinical studies
have shown the beneficial effects of plant
extracts in various pathologic conditions, which
resulted from the presence of active constituents
such as flavonoids, anthocyanins and phenolic
compounds [13,14]. Gallic acid (GA) (3,4,5-trihydroxybenzoic acid) is a phenolic compound
widely found in gall nut, green tea, hops, grapes,
red wine and oak bark. Moreover, GA could be
obtained from the acid hydrolysis of tannins, but
this conventional production of GA has high cost
and low purity. Recent studies have reported
that GA possesses various pharmacological properties, such as antioxidant, anti-inflammatory,
antimutagenic and antitumor [15,16]. Molecular
studies have shown that GA could decrease the
expression of inflammatory cytokines, such as
interleukin-1b (IL-1b), IL-6 and IL-8 in fibroblastlike synoviocytes and oral epithelial cells
[17,18]. Furthermore, GA could protect the rat
kidneys against MTX-induced toxicity by
reducing the impact of oxidative damage to tissues [15].
Considering the important MTX-induced hepatotoxicity and on the other hand antioxidant and
anti-inflammatory properties of GA, it was thought
that GA may be a promising agent to prevent
MTX-induced toxicity. Current work was therefore
carried out to examine the protective role of gallic
acid against methotrexate-induced hepatotoxicity
in rats.
2. Materials and methods
2.1. Chemicals
Gallic acid (GA), methotrexate (MTX), 5,5-dithiobis
(2-nitrobenzoic acid) (DTNB), reduced glutathione
(GSH), trichloro acetic acid (TCA), 1,1,3,3-tetraethoxypropane (TEP), 2-thiobarbituric acid (TBA), bovine
serum albumin (BSA) and Bradford reagent were
purchased from Sigma–Aldrich Chemical Company
(St. Louis, MO). All the other chemicals were prepared from Merck Company (Darmstadt, Germany).
2.2. Animals
Current study was performed according to the ethical standards and protocols approved by the
Committee of Animal Experimentation of Ahvaz
Jundishapur University of Medical Sciences, Ahvaz,
Iran (Ethic code: IR.AJUMS.REC.1395.27). Twentyeight male Wistar strain rats (weighing 180–220 g)
were obtained from the animal house of Ahvaz
Jundishapur University of Medical Science, Iran.
The animals were maintained in polypropylene
cages at a controlled condition of temperature
(20 ± 2 C) with a 12-h dark/light cycle and received
standard rat diet and water ad libitum.
2.3. Experimental procedures
The animals were randomly divided into four
experimental groups, each group includes seven
rats. Group 1 was served as control. Group 2
received a single dose of MTX (20 mg/kg, i.p.).
Group 3 received GA (30 mg/kg) orally for 10 days
and a single dose of MTX on the 9th day. Group 4
received the same dose of GA for 10 days orally.
2.4. Sample collection
After 24 h of last administration, animals were
anesthetized using a combination of ketamine and
xylazine (60/6 mg/kg, i.p.). Blood samples were collected from the jugular vein and the serum was
separated through centrifugation for 10 min at
1000 g and stored at 20 C until analysis.
Therefore, animals were sacrificed by decapitation
and the liver tissue was isolated and quickly
washed with saline. One part of the liver tissue
was fixed in phosphate-buffered formalin (10% w/
v) for histological studies and the second part of
the tissue was homogenized (1/10 w/v) in ice-cold
Tris-HCl buffer (0.1 M, pH 7.4) for biochemical estimations. The protein concentration in the homogenates was determined using Bradford assay [19].
2.5. Serum biochemical parameters
The most commonly markers reflecting liver
tissue damage or liver dysfunction include
aspartate aminotransferase (AST, formerly serum
glutamic–oxaloacetic transaminase [SGOT]), alanine
aminotransferase (ALT, formerly serum glutamate–
pyruvate transaminase [SGPT]) and alkaline phosphatase (ALP).
The ALT and AST activity was estimated using
colorimetric method of Reitman and Frankel by
ACTA CHIRURGICA BELGICA
measuring the concentration of pyruvate or oxaloacetate, produced by reaction with 2,4-dinitrophenylhydrazine [20]. The level of ALP was
determined by Belfield and Goldberg method,
using kits obtained from Randox Laboratories
Co [21].
Downloaded by [University of Florida] at 02:49 27 October 2017
2.6. Tissue biochemical parameters
2.6.1. GSH level assay
Ellman method was used to measure the tissue
homogenate GSH levels [22], based on the yellowcolored complex formation with Ellman’s Reagent
(DTNB). The homogenates were immediately precipitated with 0.1 ml of 25% TCA and then centrifuged. After centrifugation, free endogenous-SH
was assayed by transferring supernatants (0.1 ml)
to a test tube containing 2 ml of 0.5 mM DTNB (prepared in 0.2 M phosphate buffer, pH ¼ 8). Then, the
developed yellow color was read at 412 nm using a
spectrophotometer (UV-1650 PC, Shimadzu, Japan).
The standard curve was constructed over the concentration range of 1–10 mM of GSH. The GSH content was reported as nmol/mg protein.
2.6.2. MDA level assay
The MDA content was assessed as previously
described [23]. Briefly, 2.5 ml of TCA (10%, w/v) was
added to 0.5 ml of the homogenate and reaction
mixture was centrifuged at 1000 g for 10 min.
Afterward, 2 ml of each supernatant sample was
mixed with 1 ml of TBA solution (0.67%, w/v). Each
reaction mixture was heated for 10 min at 95 C,
until forming a pink-colored solution and then
cooled at room temperature. The absorbance was
measured at 532 nm by a spectrophotometer (UV1650 PC, Shimadzu, Japan). The standard curve was
constructed over the concentration range of
1–10 mM of TEP. Results were expressed as nmol/
mg protein.
2.6.3. CAT activity assay
The activity of catalase in the tissue was measured
using method explicated by Aebi [24]. Briefly, tissue homogenate was centrifuged at 12,000 g for
20 min at 4 C, then 50 ml of supernatants was
added to a cuvette containing 200 ml of phosphate
buffer, 250 ml of 0.066 M H2O2 and decrease in OD
were measured at 240 nm for 60 s. It should be
explained that one unit of enzyme activity is equal
to one mmol of H2O2 degraded/minmg1 protein.
The molar extinction coefficient of 43.6 M1cm1
at 240 nm was used to calculate the CAT activity.
3
2.6.4. SOD activity assay
The SOD activity in tissue supernatant (obtained
after centrifugation of tissue homogenate at
12,000 g for 20 min at 4 C) was measured spectrophotometrically by calculating the auto-oxidation
inhibition rate of hematoxylin, according to the
Martin method [25] and was expressed as units/mg
protein.
2.6.5. GPx activity assay
The family of glutathione peroxidase protect the
organism from oxidative stress induced damage
via reducing lipid hydroperoxides and hydrogen
peroxide to their corresponding alcohols by using
low-molecular-weight thiols, such as GSH.
The activity of GPx was measured with the GPx kit
(Randox Labs, Crumlin, UK).
2.7. Real-time RT–PCR
Total RNA was extracted from liver tissue samples
using Trizol reagent according to the manufacturer’s protocols. Then, RNA quality and concentration were evaluated by using a Nano-drop
2000 spectrophotometer (Thermo Scientific,
Wilmington, DE). Complementary DNA was synthesized by qPCRBIO cDNA synthesis kit and 0.1 lg
RNA (between 4 pg and 0.1 lg) in final volume of
20 mL. The mixture was incubated at 42 C for
30 min, followed by incubation at 85 C for 10 min
to denature RTase. QRT-PCR was carried out using
the Rotor-Gene Q 5plex HRM System (QIAGEN).
Reaction mixture contained cDNA template, 12 mL
of the QuantiNova SYBR Green PCR Master Mix,
cDNA template and specific primers (Table 1). The
typical thermal profile was set at 95 C for 5 min,
followed by 45 cycles of 95 C for 30 s, 56 C for
30 s and 72 C for 30 s. Threshold cycle (Ct) was
determined for b-actin (as endogenous control
gene) and target genes of each sample. DCt and
subsequently relative gene expressions were calculated for each sample. The primers used are summarized in Table 1.
2.8. Histopathological examination
In order to examine histological changes, small
pieces of liver were submerged with 10%
Table 1. The primers used in real-time RT–PCR.
Primer
Sequence
SOD2
Forward: 50 -AGCTGCACCACAGCAAGCAC-30 (sense)
Reverse: 50 -TCCACCACCCTTAGGGCTCA-30 (antisense)
Forward: 50 -CGGTTTCCCGTGCAATCAGT-30 (sense)
Reverse: 50 -ACACCGGGGACCAAATGATG-30 (antisense)
Forward: 50 -GGCATCCTGACCCTGAAGTA-30 (sense)
Reverse: 50 -GGGGTGTTGAAGGTCTCAAA-30 (antisense)
GPx1
b-actin
4
F. SAFAEI ET AL.
Downloaded by [University of Florida] at 02:49 27 October 2017
Figure 1. Effect of GA on serum parameters in MTX-induced toxicity in rats. Values are means ± SD (n ¼ 7). Data were analyzed
by one-way ANOVA test followed by Tukey’s post hoc test for multiple comparisons. GA: gallic acid. MTX: Methotrexate.
significant difference in comparison with the control group (p<.001). #significant difference in comparison with the MTX
group (###p<.001).
Figure 2. The effect of pretreatment with GA on MDA and GSH levels in liver tissues in MTX-induced oxidative stress. The values are presented as means ± SD (n ¼ 7). The data were analyzed by one-way ANOVA test, followed by Tukey’s post hoc test for
multiple comparisons. GA: gallic acid. MTX: methotrexate. significant difference in comparison with the control group
(p<.001). #significant difference in comparison with the MTX group (#p < .05).
phosphate-buffered formalin for 24 h, embedded
in paraffin, sectioned at 5 mm and then stained
with hematoxylin and eosin (H&E) for light microscopic observations. In each liver tissue section, 25
fields were analyzed.
2.9. Statistical analysis
The results were reported as means ± SD. The data
were analyzed by one-way ANOVA test followed
by Tukey’s post hoc test for multiple comparisons.
Data analysis was performed using the Prism 5.0
(San Diego, CA) statistical package program.
p Value less than .05 was considered significant.
3. Results
decreased (p < .001), these markers levels compared to MTX group (Figure 1).
3.2. Effect of MTX and GA on MDA and GSH
levels
The results indicated that MDA level, a lipid peroxidation index, was significantly elevated in liver of
rats exposed to MTX when compared to the control group (p < .001) pretreatment with GA did not
change MDA level compared to MTX group.
The level of GSH significantly (p < .001)
decreased in the liver of rats exposed to MTX and
pretreatment with GA significantly (p < .05) inhibited the MTX-induced reduction of GSH content
(Figure 2).
3.1. Effect of MTX and GA on serum markers
3.3. Effect of MTX and GA on enzymatic
antioxidant activity
Result showed that 24 h after MTX administration
rats developed hepatotoxicity that was reflected
by a significant increase (p < .001) in the levels of
AST, ALT, ALP in comparison with the control
group, while pretreatment with GA significantly
As shown in Figure 3, MTX significantly decreased
CAT, GPx and SOD activity compared to control
group (p < .001). Pretreatment with GA significantly
inhibited the MTX-induced reduction of CAT
(p < .05), GPx (p < .001) and SOD activity (p < .001).
ACTA CHIRURGICA BELGICA
5
Downloaded by [University of Florida] at 02:49 27 October 2017
Figure 3. The effect of pretreatment with GA on CAT, GPx and SOD activity in MTX- induced oxidative stress. The values are
presented as means ± SD (n ¼ 7). The data were analyzed by one-way ANOVA test, followed by Tukey’s post hoc test for multiple comparisons. GA: gallic acid. MTX: Methotrexate. significant difference in comparison with the control group (p<.001).
#significant difference in comparison with the MTX group (#p<.05, ##p<.01, ###p<.001).
changes including inflammation and necrosis
in comparison with the MTX-treated group
(Figure 5(C), Table 2).
4. Discussion
Figure 4. The effect of pretreatment with GA on GPx and
SOD gene expressions in MTX-induced oxidative stress. The
values are presented as means ± SD (n ¼ 7). The data were
analyzed by one-way ANOVA test, followed by Tukey’s post
hoc test for multiple comparisons. GA: gallic acid. MTX:
methotrexate. significant difference in comparison with the
control group (p<.001). #significant difference in comparison with the MTX group (##p < 0.01, ###p<.001).
3.4. Effect of MTX and GA on SOD2 and GPx1
gene expressions
The results obtained from real-time RT–PCR analysis indicated that the expression of SOD2 and
GPx1 genes significantly decreased in MTX-treated
groups in comparison with the control group
(p < .001) and pretreatment with GA significantly
inhibited the MTX-induced reduction of the expression of SOD2 (p < .01) and GPx1 (p < .001) genes
(Figure 4).
3.5. The light microscopic findings
The histopathological changes in rat livers were
examined in H&E-stained sections. In MTX-treated
group, severe changes were observed in liver
morphology, including hepatocytes necrosis, accumulation of inflammatory cells in priportal area,
and cell swelling in hepatocytes around the central
vein compared to the control group (Figure 5(A,B),
Table 2). Treatment with GA improved histological
Present study reports the potential protective
effects of gallic acid against MTX-induced toxicity
by studying the numerous biological activities
including hepatoprotective activity.
In addition to anticancer activity, chemotherapeutic drugs cause toxic side effects in various
organs such as liver [26].
MTX is one of the commonly used chemotherapeutic agents that additionally used to treat
rheumatoid diseases at low doses [8]. However,
various side effects such as hepatotoxicity, intestinal injury and suppression of bone marrow-limiting MTX efficacy. [27]. In the liver, MTX has been
shown to be converted to MTX-Glu by an enzymatic system and stored in hepatocytes leading to
longer intracellular presence of MTX in the tissue
and subsequent induction of oxidative and inflammatory damage [28].
However, recent studies have demonstrated
that phytochemicals could protect organs and tissues against drug and toxin-induced damages
[29–32].
Gallic acid is a phenolic compound widely found
in the plant kingdom with numerous biological
and pharmacological activities including antioxidant, anticancerous, anti-inflammatory as we as
hepatoprotective activity [33,34].
Current results indicated that AST and ALT activity, considered as reliable indices of hepatotoxicity
[35,36], increased in MTX-treated group indicating
structural damage to the liver. However, treatment
with GA ameliorated the MTX-induced cellular
damages which this results were in agreement
Downloaded by [University of Florida] at 02:49 27 October 2017
6
F. SAFAEI ET AL.
Figure 5. Photomicrographs of liver in the seven experimental group (H&E). Magnification x 400. (A) Control group, normal
architecture of histological section of rat liver. (B) MTX-treated group, Note to necrotic cells with eosinophilic cytoplasm in compare with normal cells and pyknotic nuclei also ballooning degeneration with free space in hepatocytes is evident.
(C) MTX þ GA-treated group, (D) GA-treated group.
Table 2. The histopathological changes of rat livers in H&Estained sections.
Groups
Histological Criteria
Congestion of RBC
Infiltration of inflammatory cells
Fat deposit (%)
Pyknosis (%)
a
Control
0.0
0.0
0.0
0.0
MTX
MTX þ GA
1.6 ± 0.27a 0.8 ± 0.2b
2.1 ± 0.28a 1.1 ± 0.16b
27.5 ± 4.2a 12.2 ± 2.6b
35.5 ± 5.8a 18.4 ± 4.3b
GA
0.0
0.0
0.0
0.0
significant with control group.
significant with MTX group.
b
with previous findings on the hepatoprotective
activity of GA [37,38].
Oxidative stress is known to be one of the main
causative factors involved in the toxicological
effects of most of chemotherapeutic drugs.
Methotrexate induces oxidative stress via inhibition
of NADPH availability required for maintaining
reduced state of glutathione by glutathione reductase [39,40]. Moreover, MTX induces nitrative stress
through induction of inducible nitric oxide synthase (iNOS) and increase the production of
NO [41].
Considering that MTX induces oxidative stress in
liver tissue, the measurement of MDA levels,
antioxidant enzyme activity and GSH content was
thought to be a valuable in the diagnosis of MTXinduced liver toxicity.
MDA is one of the reactive products resulted
from the oxidative degradation of membrane
unsaturated fatty acid, owning toxic properties.
Increased levels of MDA have been linked to various human disorders [42,43]. Our results showed
that MTX significantly increased the MDA levels in
liver tissue and treatment with GA could not
reduce MTX-induced elevated MDA concentration.
Although in our study GA did not decrease MDA
level, GA may affect the level of other lipid oxidation products, such as 4-hydroxynonenal, that did
not measure in this study.
There are evidences indicating that exogenous
antioxidants could protect liver tissue from MTXinduced damage [44]. Endogenous antioxidants,
such as GSTs, catalyzing the conjugation of GSH to
exogenous and endogenous electrophiles, GPx,
oxidizing GSH to glutathione disulfide (GSSG), SOD,
dismutasing O2. to H2O2 and molecular oxygen,
CAT, converting H2O2 to water and oxygen, and
GSH, the low-molecular-weight antioxidants, are
Downloaded by [University of Florida] at 02:49 27 October 2017
ACTA CHIRURGICA BELGICA
the first line defense against a variety of reactive
toxicants [45–49].
Results from our study relieved that MTX significantly decreased the activity of SOD, CAT and GST
and mRNA expression of SOD and CAT genes as
well as GSH content in liver tissue. Based on current results and previously published studies, the
oxidative liver tissue harm induced by elevated
level of lipid peroxidation may be occasioned by
lowering the amount of antioxidant enzymes in
the animal exposed to MTX [6,41].
However, treatment with GA could enhance the
MTX-induced decreased antioxidant enzymes activity and GSH content. The obtained results were in
agreement with previous studies indicating that GA
effectively reduces nitrosodiethylamine, paracetamol, lead and carbon tetrachloride–induced liver
damage through improving antioxidant defenses
and reducing inflammatory responses [34,38,50,51].
5. Conclusions
The results of this study suggest that oral gallic
acid can protect liver tissue from oxidative damages induced by methotrexate through modification of antioxidant enzymes activities and
nonenzymatic antioxidant levels. Direct or indirect
antioxidant properties of gallic acid can decrease
oxidative stress-induced injuries in liver tissue
exposed to methotrexate. Our results demonstrated that gallic acid may be employed as a
promising natural herbal product to prevent oxidative stress-induced liver damage in patients receiving chemotherapeutic drugs.
Disclosure statement
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
All authors declare no conflict of interest related to the
present work.
[11]
Funding
This work was supported by the grant number 94s163 provided by Deputy of Research of Ahvaz Jundishapur
University of Medical Sciences, Ahvaz, Iran.
[12]
ORCID
[13]
Saeed Mehrzadi
http://orcid.org/0000-0001-6619-2330
Mojtaba Dolatshahi
http://orcid.org/0000-0002-33419989
[14]
[15]
References
[1]
O'Dell J, Takeuchi T, Tanaka Y, et al. OP0226 randomized, double-blind study comparing Chs-0214 with
7
etanercept in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. Ann
Rheum Dis. 2016;75(Suppl 2):143–143.
Group NGTAT. Superiority of sequential methotrexate, fluorouracil, and leucovorin to fluorouracil alone
in advanced symptomatic colorectal carcinoma: a
randomized trial. J Clin Oncol. 2016;7:1437–1446.
Ferreri AJ, Cwynarski K, Pulczynski E, et al.
Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in
patients with primary CNS lymphoma: results of
the first randomisation of the International
Extranodal
Lymphoma
Study
Group-32
(IELSG32) phase 2 trial. Lancet Haematol. 2016;3:
e217–e227.
Yang W, Zou Y, Meng F, et al. Efficient and targeted
suppression of human lung tumor xenografts in
mice with methotrexate sodium encapsulated in allfunction-in-one chimeric polymersomes. Adv Mater.
2016;28:8234–8239.
Lee EB, Fleischmann R, Hall S, et al. Tofacitinib versus
methotrexate in rheumatoid arthritis. N Engl J Med.
2014;370:2377–2386.
Feagan BG, McDonald JW, Panaccione R, et al.
Methotrexate in combination with infliximab is no
more effective than infliximab alone in patients with
Crohn's
disease.
Gastroenterology.
2014;146:
681–688. e1.
Roubille C, Richer V, Starnino T, et al. The effects of
tumour necrosis factor inhibitors, methotrexate, nonsteroidal anti-inflammatory drugs and corticosteroids
on cardiovascular events in rheumatoid arthritis,
psoriasis and psoriatic arthritis: a systematic review
and meta-analysis. Ann Rheum Dis. 2015.
Aslibekyan S, Sha J, Redden DT, et al. Gene-body
mass index interactions are associated with methotrexate toxicity in rheumatoid arthritis. Ann Rheum
Dis. 2014;73:785–786.
Fang YZ, Yang S, Wu G. Free radicals, antioxidants,
and nutrition. Nutrition. 2002;18:872–879.
Vardi N, Parlakpinar H, Ozturk F, et al. Potent protective effect of apricot and b-carotene on methotrexate-induced intestinal oxidative damage in rats.
Food Chem Toxicol. 2008;46:3015–3022.
Robaczewska J, Kedziora-Kornatowska K, Kozakiewicz
M, et al. Role of glutathione metabolism and glutathione-related antioxidant defense systems in hypertension. J Physiol Pharmacol. 2016;67:331–337.
Shah MA, Bosco SJD, Mir SA. Plant extracts as natural
antioxidants in meat and meat products. Meat Sci.
2014;98:21–33.
Roleira FM, Tavares-da-Silva EJ, Varela CL, et al. Plant
derived and dietary phenolic antioxidants: anticancer
properties. Food Chem. 2015;183:235–258.
Szymanska R, Pospisil P, Kruk J. Plant-derived antioxidants in disease prevention. Oxid Med Cell Longev.
2016;2016:1920208.
Daglia M, Di Lorenzo A, F, Nabavi S, et al.
Polyphenols: well beyond the antioxidant capacity:
gallic acid and related compounds as neuroprotective agents: you are what you eat!. CPB.
2014;15:362–372.
8
F. SAFAEI ET AL.
[16]
Lima KG, Krause GC, Schuster AD, et al. Gallic acid
reduces cell growth by induction of apoptosis and
reduction of IL-8 in HepG2 cells. Biomed
Pharmacother. 2016;84:1282–1290.
Asnaashari M, Farhoosh R, Sharif A. Antioxidant
activity of gallic acid and methyl gallate in triacylglycerols of Kilka fish oil and its oil-in-water emulsion.
Food Chem. 2014;159:439–444.
Roby MHH, Sarhan MA, Selim KA-H, et al.
Evaluation of antioxidant activity, total phenols and
phenolic compounds in thyme (Thymus vulgaris L.),
sage (Salvia officinalis L.), and marjoram (Origanum
majorana L.) extracts. Ind Crops Prod. 2013;43:
827–831.
Bradford MM. A rapid and sensitive method for the
quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal
Biochem. 1976;72:248–254.
Reitman S, Frankel S. A colorimetric method for the
determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol.
1957;28:56–63.
Belfield A, Goldberg D. Colorimetric determination of
alkaline phosphatase activity. Enzyme. 1971;12:
561–568.
Ellman GL. Tissue sulfhydryl groups. Arch Biochem
Biophys. 1959;82:70–77.
Buege JA, Aust SD. Microsomal lipid peroxidation.
Meth Enzymol. 1978;52:302–310. doi: 10.1016/S00766879(78)52032-6.
Aebi H. Catalase in vitro. Meth Enzymol.
1984;105:121–126.
Martin JP, Jr Dailey M, Sugarman E. Negative and
positive assays of superoxide dismutase based on
hematoxylin autoxidation. Arch Biochem Biophys.
1987;255:329–336.
Reiter RJ, Tan D, Sainz RM, et al. Melatonin: reducing
the toxicity and increasing the efficacy of drugs.
J Pharm Pharmacol. 2002;54:1299–1321.
Lopez-Lopez E, Martin-Guerrero I, Ballesteros J, et al.
A systematic review and meta-analysis of MTHFR
polymorphisms in methotrexate toxicity prediction
in pediatric acute lymphoblastic leukemia.
Pharmacogenomics J. 2013;13:498–506.
Willner N, Storch S, Tadmor T, et al. Almost a tragedy: severe methotrexate toxicity in a hemodialysis
patient treated for ectopic pregnancy. Eur J Clin
Pharmacol. 2014;70:261–263.
Javad-Mousavi SA, Hemmati AA, Mehrzadi S, et al.
Protective effect of Berberis vulgaris fruit extract
against Paraquat-induced pulmonary fibrosis in rats.
Biomed Pharmacother. 2016;81:329–336.
Ghaznavi H, Mehrzadi S, Dormanesh B, et al.
Comparison of the protective effects of melatonin
and silymarin against gentamicin-induced nephrotoxicity in rats. J Evid Based Complementary Altern
Med. 2016;21:NP49–NP55.
Rashidian A, Roohi P, Mehrzadi S, et al.
Protective effect of ocimum basilicum essential oil
against acetic acid–induced colitis in rats. J Evid
Based Complementary Altern Med. 2016;21:
NP36–NP42.
[17]
[18]
[19]
Downloaded by [University of Florida] at 02:49 27 October 2017
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
Najafzadeh H, Rezaie A, Masoodi A, et al.
Comparison of the effect of vanadium and deferoxamine on acetaminophen toxicity in rats. Indian J
Pharmacol. 2011;43:429.
Faried A, Kurnia D, Faried L, et al. Anticancer
effects of gallic acid isolated from Indonesian
herbal medicine, Phaleria macrocarpa (Scheff.)
Boerl, on human cancer cell lines. Int J Oncol.
2007;30:605–613.
Wang J, Tang L, White J, et al. Inhibitory effect of
gallic acid on CCl4-mediated liver fibrosis in mice.
Cell Biochem Biophys. 2014;69:21–26.
Ozer J, Ratner M, Shaw M, et al. The current state of
serum biomarkers of hepatotoxicity. Toxicology.
2008;245:194–205.
Chen L, Pan D-D, Zhou J, et al. Protective effect of
selenium-enriched Lactobacillus on CCl4-induced
liver injury in mice and its possible mechanisms.
WJG. 2005;11:5795.
Nabavi SF, Nabavi SM, Habtemariam S, et al.
Hepatoprotective effect of gallic acid isolated from
Peltiphyllum peltatum against sodium fluorideinduced oxidative stress. Ind Crops Prod.
2013;44:50–55.
Rasool MK, Sabina EP, Ramya SR, et al.
Hepatoprotective and antioxidant effects of gallic
acid in paracetamol-induced liver damage in mice.
J Pharm Pharmacol. 2010;62:638–643.
€
Çak{r T, Ozkan
E, Dulundu E, et al. Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced
hepatorenal oxidative injury in rats. J Pharm
Pharmacol. 2011;63:1566–1571.
lu-Demiralp E, Cetiner M, et al.
Şener G, Ekşiog
L-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell
Biol Toxicol. 2006;22:47–60.
Saka S, Aouacheri O. The Investigation of the oxidative stress-related parameters in high doses methotrexate-induced albino wistar rats. J Bioequiv
Availab. 2017;9:372–376.
Moazamian R, Polhemus A, Connaughton H, et al.
Oxidative stress and human spermatozoa: diagnostic
and functional significance of aldehydes generated
as a result of lipid peroxidation. Mol Hum Reprod.
2015;21:502–515.
~oz MF, Arg€
Ayala A, Mun
uelles S. Lipid peroxidation:
production, metabolism, and signaling mechanisms
of malondialdehyde and 4-hydroxy-2-nonenal. Oxid
Med Cell Longev. 2014;2014:360438.
Abdel-Daim MM, Khalifa HA, Abushouk AI, et al.
Diosmin attenuates methotrexate-induced hepatic,
renal, and cardiac injury: a biochemical and histopathological study in mice. Oxid Med Cell Longev.
2017;2017:3281670.
Ghaznavi H, Mehrzadi S, Dormanesh B, et al.
Comparison of the protective effects of melatonin
and silymarin against gentamicin-induced nephrotoxicity in rats. J Evid Based Complementary Altern
Med. 2016;21:NP49–55.
Mehrzadi S, Kamrava SK, Dormanesh B, et al.
Melatonin synergistically enhances protective effect
of
atorvastatin
against
gentamicin-induced
ACTA CHIRURGICA BELGICA
[47]
Downloaded by [University of Florida] at 02:49 27 October 2017
[48]
nephrotoxicity in rat kidney. Can J Physiol
Pharmacol. 2015;94:265–271.
Hernandez LE, Sobrino-Plata J, Montero-Palmero MB,
et al. Contribution of glutathione to the control of
cellular redox homeostasis under toxic metal and
metalloid stress. J Exp Bot. 2015;66:2901–2911.
Ishii T, Mann GE. Redox status in mammalian
cells and stem cells during culture in vitro: critical roles of Nrf2 and cystine transporter activity
in the maintenance of redox balance. Redox Biol.
2014;2:786–794.
[49]
[50]
[51]
9
Traverso N, Ricciarelli R, Nitti M, et al. Role of glutathione in cancer progression and chemoresistance.
Oxid Med Cell Longev. 2013;2013:972913.
Latief U, Husain H, Mukherjee D, et al.
Hepatoprotective efficacy of gallic acid during
Nitrosodiethylamine-induced liver inflammation in
Wistar rats. J Basic Appl Zool. 2016;76:31–41.
DM, et al.
Reckziegel P, Dias VT, Benvegnu
Antioxidant protection of gallic acid against toxicity
induced by Pb in blood, liver and kidney of rats.
Toxicol Rep. 2016;3:351–356.
Документ
Категория
Без категории
Просмотров
6
Размер файла
1 893 Кб
Теги
2017, 1394672, 00015458
1/--страниц
Пожаловаться на содержимое документа