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Antioxidant Activities of Celery and Parsley Juices in Rats Treated with Doxorubicin

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We have examined the influence of diluted pure celery and parsley leaf and root juices and their combinations with doxorubicin on the antioxidant status [as measured by the content of reduced glutathione (GSH) and ferric reducing antioxidant power (FRAP)] in liver homogenate and hemolysate and on the contents of cytochrome P450 in liver homogenate. It was found that doxorubicin significantly decreased the content of reduced glutathione and the total antioxidative status (FRAP) in liver homogenate and hemolysate, while celery and parsley juices alone and in combination with doxorubicin had different actions. Doxorubicin and celery juice had no effect on content of cytochrome P450. However, in combination with doxorubicin, parsley root juice significant increased, and parsley leaves juice decreased the cytochrome P450 content (compared to doxorubicin treated animals). Only parsley root juice significantly increased the content of cytochrome P450.
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Molecules 2010, 15, 6193-6204; doi:10.3390/molecules15096193
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Antioxidant Activities of Celery and Parsley Juices in Rats
Treated with Doxorubicin
Jovanka Kolarovic
1
, Mira Popovic
2,
*, Janka Zlinská
3
, Svetlana Trivic
2
and Matilda Vojnovic
4
1
Institute for Child and Youth Health Care of Vojvodina, Department of Hematology/Oncology,
Novi Sad, Serbia, E-Mail: jovanka.kolarovic@gmail.com (J.K.)
2
Department of Chemistry, Faculty of Science, University of Novi Sad, Serbia
3
University of Central Europe in Skalica, Slovakia
4
The Health Center, 21000 Novi Sad, Serbia
* Author to whom correspondence should be addressed; E-Mail: mira.popovic@dh.uns.ac.rs;
Tel.: +38-121-485-2770; Fax: +38-121-454-065.
Received: 23 July 2010; in revised form: 27 August 2010/ Accepted: 2 September 2010 /
Published: 3 September 2010
Abstract: We have examined the influence of diluted pure celery and parsley leaf and root
juices and their combinations with doxorubicin on the antioxidant status [as measured by
the content of reduced glutathione (GSH) and ferric reducing antioxidant power (FRAP)]
in liver homogenate and hemolysate and on the contents of cytochrome P450 in liver
homogenate. It was found that doxorubicin significantly decreased the content of reduced
glutathione and the total antioxidative status (FRAP) in liver homogenate and hemolysate,
while celery and parsley juices alone and in combination with doxorubicin had different
actions. Doxorubicin and celery juice had no effect on content of cytochrome P450.
However, in combination with doxorubicin, parsley root juice significant increased, and
parsley leaves juice decreased the cytochrome P450 content (compared to doxorubicin
treated animals). Only parsley root juice significantly increased the content of
cytochrome P450.
Keywords: celery and parsley juices; doxorubicin; reduced glutathione; FRAP; Cyt P450
OPEN ACCESS
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1. Introduction
Doxorubicin is among the most effective and widely used cytotoxic drugs from the anthracycline
group. It is used in treatment of acute leukemias, lymphomas and different types of solid tumors such
as breast, liver and lung cancers. Doxorubicin is significantly toxic to most tissues, organs and systems
of organs. It is extremely toxic to the heart and can cause permanent damage and even death. There is
increasing evidence that essential components of myocardial energy metabolism are among the highly
sensitive and early targets of doxorubicin-induced damage [1,2].
It is thought that doxorubicin causes antioxidative stress by inducing free oxygen radicals that lead
to lipid peroxidation in mitochondrial membranes and the sarcoplasmatic reticulum, thus damaging
cardiac muscle. Different authors have tried to combine potentially cardiotoxic drugs with extracts of
medical herbs used as herbal remedy, in an attempt to reduce their side effects [3,4], as antioxidants
from natural sources may be useful in the protection of doxorubicin induced cardiotoxicity [4,5].
Parsley (Petroselinum hortense Hoffm. 1814; the earlier botanical name Petroselinum crispum [Mill.]
Nyman ex A. W. Hill, Apiaceae; in 1764. Linnaeus classified it Apium petroselinum L.) contains
flavonoids (apiin and luteolin) and essential oil (apiol and myristicin), responsible for both the medical
uses and toxicity of parsley. Furanocoumarins (psoralen, bergapten, isoimperatorin, oxypeucedanin,
xanthoxin, trioxalen and angelicin) are other important chemical constituents of parsley plants [6,7].
In folk medicine parsley is used for menstrual disorder ailments, as an emmenagogue, galactagogue
and stomachic, and externally against head lice. Results of numerous investigations point out to the
antioxidant properties of parsley. For example, the flavonoid apigenin, one of the components of
parsley plant, was shown to express strong antioxidant effects by increasing the activities of
antioxidant enzymes and related to that, decreasing the oxidative damage to tissues. Potential for
anticancer activity by parsley was reported as well [7,8].
Celery (Apium graveolens L. Sp. Pl. 264 (1753), Apiaceae) is a medicinal herb used as a food, and
also in traditional medicine. It contains aromatic substances in the roots, stem and leaves. The healing
properties of celery are due to the essential oil and flavonoids, mostly apiin and apigenin. Celery
contains an essential oil (d-limonene and selinene, santalol, eudesmol, apiol myristicin, etc) [7,9].
The essential oil from celery exhibits antifungal and antibacterial actions. Celery can lower blood
pressure and regulate heart function. Celery can be used to slow down and treat complications caused
by diabetes because it influences the blood glucose level by stimulating the pancreas to insulin
secretion [7].
It is well known that celery can cause photodermatitis and contact dermatitis and act as aphrodisiac.
It can cause sedation and irritation and be responsible for spasmolytic action. A number of chemical
compounds present in celery seeds show antiinflammatory and analgesic effects. Apigenin from celery
seed exhibits an antiaggregation effect in vitro. It is reported to inhibit contractions of the isolated
smooth muscle of the thoracic aorta [7].
Some flavonoids have mutagenic and/or prooxidant effects. Cytochromes P450 (CYPs),
monooxygenases metabolizing xenobiotics (e.g. drugs, carcinogens) interact with flavonoids and other
endogenous substrates. Flavonoids induce the expression of several CYPs and modulate (inhibit or
stimulate) their metabolic activity. Some CYPs participate in metabolism of flavonoids. If the
Molecules 2010, 15
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flavonoids are coadministered with other drugs, careful attention should be paid to the metabolism
because of possible interactions [10].
Numerous studies show that active principles from plants have multiple effects on metabolism and
may alter activity of different drugs. Secondary biomolecules from plants might have diverse effects
such as: antibacterial and antiviral activity, anti-inflammatory, anti-angionic, analgesic and antiallergic
effects, hepatoprotective, cytotoxic, apoptotic, estrogenic and antiestrogenic properties, antioxidant
and prooxidant effects, etc. [11-13].
Our previous results have pointed at antioxidant and hepatoprotective effects of celery and parsley
extracts, as well as influence on pharmacodynamic activities [7]. These findings have led us to examine
the influence of celery and parsley root and leaf juices on total antioxidant status and content of reduced
glutathione in liver homogenate and hemolysate in doxorubicin treated rats. We also investigated the
effect of treatment with doxorubicin (alone and in combination with celery and parsley roots and leaves
juices) on the cytochrome P450 content.
2. Results and Discussion
In liver homogenate the content of reduced glutathione was significantly decreased by parsley leaf
juices and doxorubicin (Figure 1). Parsley root and leaf juices and their combination with doxorubicin
caused a significant increase in GSH content compared to doxorubicin alone. Since the content of
reduced GSH is the important indicator of antioxidative status, we can conclude that positive
synergism was observed.
Figure 1. Content of reduced glutathione in liver homogenate of animals treated with
doxorubicin, parsley leaves and roots juices and their combination. t-test, n = 6; compared
to CON group: * p < 0.05, compared to D group:
a
p < 0.05.
In blood hemolysate reduced glutathione content was significantly decreased by parsley leaf juice,
doxorubicin and by a combination of doxorubicin and parsley leaf juice (Figure 2). Parsley leaf juice in
combination with doxorubicin caused a reduction in GSH content compared to doxorubicin alone.
CON PR PL D PRD PLD
0
2
4
6
8
10
12
14
nmol GSH/mg of proteins
*
*
a a
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Figure 2. Content of reduced glutathione in blood hemolysate of animals treated
doxorubicin, parsley leaves and roots juices and their combination. t-test, n = 6; compared
to CON group: * p <0.05, compared to D group:
a
p <0.05.
In liver homogenate the content of reduced glutathione was significantly increased by celery root
and leaf juices and decreased by doxorubicin and combinations of doxorubicin and celery root juice. In
blood hemolysate reduced glutathione content was significantly decreased only by doxorubicin [3]. As
expected, doxorubicin reduced the GSH content in liver homogenate and blood hemolysate.
In our previous research, celery and parsley have exhibited protective effects in liver homogenate
and in blood hemolysate of experimental animals treated with doxorubicin or CCl
4
[3,14]. The growth
inhibitory activity of doxorubicin or cisplatin, as a single agent, may be modified by combinations of
Phyllanthus emblica or Terminalia bellerica extracts and be synergistically enhanced in some cases [15].
Prevention of doxorubicin induced oxidative stress damage of rat heart by sesame oil, supports the
hypothesis that at least part of the mechanism of cardiotoxicity could be attributed to the
overproduction of free radicals. Oxidative damage to heart contributes to the myocardial toxicity
induced by doxorubicin in male rats. These effects might be limited by the use of sesame oil whose
protective effects may be due to its antioxidant properties [16].
Beyond this, many investigators have proposed that oxidative stress is an important component of
the toxicity caused by most chemicals that are activated to electrophiles. Electrophiles also deplete
reduced glutathione, one of the defenses against damage from reactive oxygen species such as
hydroperoxides. Even more subtle changes in the redox balance of a cell may be critical, in that many
transcription factors and other signaling systems are controlled by redox events [17].
Figure 3 presents the antioxidative status of liver homogenate of experimental animals. As
expected, celery root juice significantly increased the antioxidative capacity compared to control,
while doxorubicin reduced it. In combination of doxorubicin and celery root and leaf juices, positive
synergism was observed and the antioxidative capacity was significantly higher. Recently, much
attention has been focused on the protective effects of antioxidants and naturally occurring substances
against doxorubicin -induced cardiotoxicity [16].
CON PR PL D PRD PLD
0
0.5
1
1.5
2
µ
mol GSH/L of erythrocytes
*
*
a
*
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Figure 3. Effects of doxorubicin, celery leaf and root juices and their combination on
FRAP antioxidant capacities in liver homogenate. t-test, n = 6; compared to CON group:
* p < 0.05, compared to D group:
a
p < 0.05.
In a paper by Sugiyama et al. it was shown that patients who had drank green tea or theanine was
added to their food exhibited less severe side effects from doxorubicin treatments [18]. Production of
antibacterial proteins in the blood was up to five times higher in the tea-drinkers, an indicator of a
stronger immune response [19].
In hemolysate, doxorubicin and combination of doxorubicin and both celery juices (leaves and
roots) reduced antioxidative capacity compared to the control (CON) (Figure 4). It is interesting to
note that combinations of celery roots and leaves juices with doxorubicin (CRD and CLD)
significantly reduced FRAP when compared to doxorubicin. This could be explained by presence of
prooxidant flavonoids with a phenolic B ring, especially those with one ring [20], although they
primarily act as antioxidants [21].
Figure 4. Effects of doxorubicin, celery leaf and root juices and their combination on
FRAP antioxidant capacities in hemolysate. t-test, n = 6; compared to CON group:
* p < 0.05, compared to D group:
a
p < 0.05.
CON CR CL D CRD CLD
0
2
4
6
8
10
12
14
16
18
FRAP (µM/mg of proteins)
*
*
a
a
*
CON CR CL D CRD CLD
0
200
400
600
800
1000
1200
FRAP (µM/L)
*
*
a
*
a
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In Figure 5 it is obvious that all parsley and celery juices, doxorubicin and their combination
significantly reduced FRAP in liver homogenate. It is interesting that parsley juices increase
antioxidative capacity [21], although some references indicate that extracts of parsley have
prooxidative properties [22]. Doxorubicin as a cytotoxic drug causes reduction of antioxidative
capacity with similar FRAP values as parsley juices. The combination of the medicine and parsley
juices did not show positive synergism (Figure 5).
Figure 5. Effects of doxorubicin, parsley leaf and root juices and their combination on
FRAP antioxidant capacities in liver homogenate. t-test, n = 6; compared to CON group:
* p < 0.05, compared to D group:
a
p < 0.05.
Results obtained by determination of total antioxidative status in liver homogenate were very
similar to the results of investigation of antioxidative status in blood hemolysate of rats treated with
parsley juices, doxorubicin and their combinations (Figure 6).
Figure 6. Effects of doxorubicin, parsley leaf and root juices and their combination on
FRAP antioxidant capacities in hemolysate. t-test, n = 6; compared to CON group:
* p < 0.05, compared to D group:
a
p < 0.05.
CON PR PL D PRD PLD
0
2
4
6
8
10
12
14
FRAP (µM/mg of proteins)
*
*
*
*
*
CON PR PL D PRD PLD
0
200
400
600
800
1000
1200
FRAP (µM/L)
*
*
*
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Parsley root juice (PR) significantly increased the content of Cyt P450, while the combination of
parsley leaf juice with doxorubicin (PLD) significantly decreased it in liver homogenate when
compared to untreated animals (CON). Treatments with doxorubicin, parsley leaf juice and their
combination significantly reduced the content of Cyt P450, while treatments with root juice
significantly increased it (Figure 7).
Figure 7. Effects of doxorubicin, parsley leaves and roots juices and their combination on
Cyt P450 in liver homogenate. t-test, n = 6; compared to CON group: * p < 0.05, compared
to D group:
a
p < 0.05.
Celery root and leaf juices applied alone and in combination with doxorubicin did not change the
content of Cyt P450 in liver homogenate when compared to the control (Figure 8).
Figure 8. Effects of doxorubicin, celery leaves and roots juices and their combination on
Cyt P450 in liver homogenate. t-test, n = 6; compared to CON group: * p < 0.05, compared
to D group:
a
p < 0.05.
A number of naturally occurring flavonoids have been shown to modulate the CYP450 system,
including the induction or inhibition of these enzymes [10]. Based on determined protein levels and
CON PR PL D PRD PLD
0
2
4
6
8
10
12
Cyt P450 (nmol/g of liver)
*
*
a
a
CON CR CL D CRD CLD
0
2
4
6
8
10
12
14
Cyt P450 (nmol/g of liver)
Molecules 2010, 15
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specific enzyme activities, isoquercitrin, (a constituent of celery plants) was the most efficient inducer
of CYP1A1 and CYP1A2 in rat liver. On the other hand, the aglycone quercetin had no effect on the
protein levels, but caused a concentration-dependent increase of CYP1A1 mRNA in MCF7 cells [23].
In normal metabolism Cyt P450 produce H
2
O
2
and O
2
. Formation of reactive oxygen species
(ROS) can be induced or inhibited with various xenobiotics. The rates of oxygen reduction are very
fast in vitro but could easily be measured. The question can be raised as to whether these are equally
fast in vivo [17].
3. Experimental
3.1. Plant Material
Whole plants of cultivated Petroselinum hortense Hoffm. 1814., and Apium graveolens L were
collected in Juny 2009 at Veternik (Vojvodina province), Republic of Serbia. The voucher specimens
Petroselinum hortense Hoffm. 1814, No 2-1797, Serbia, Novi Sad, Veternik (UTM 34T DR 2 01),
26.06.2009., det.: Goran Anačkov and Apium graveolens L. 1753, No 2-1798, Serbia, Novi Sad,
Veternik (UTM 34T DR 2 01), 26.06.2009., det.: Goran Anačkov were confirmed and deposited at the
Herbarium of the Department of Biology and Ecology (BUNS Herbarium), Faculty of Natural
Sciences, University of Novi Sad.
Whole fresh plants were used in this study. Juices of celery and parsley leaves and roots were
prepared identically. Leaves were separated from roots. Fresh leaves were ground in a blender and
5% solution (v/v) was prepared by diluting pure juice with distilled water. The same blender was used
for grounding roots and a 5% (v/v) solution was prepared by diluting with distilled water.
3.2. Animal Treatment
This investigation was conducted on sexually mature male Whistar laboratory rats, with an average
body weight of 250-300 grams and ages up to 3 months. Animal care and all experimental procedures
were conducted in accordance with the Guide for the Care and Use of Laboratory Animal Resources,
edited by Commission of Life Sciences, National Research Council, Male and female Hanover
National Medical Institute (Hann NMRI). Rats were bred in the vivarium at the Department of
Pharmacology, Toxicology and Clinical Pharmacology, Medical Faculty, University of Novi Sad,
Serbia. Animals were kept in standard plexiglass cages at constant room temperature 21 ± 1ºC and
humidity 55% ± 1.5%, with circadian rhythm (day/night). They were fed standard laboratory rat feed,
produced by the Veterinary Institute in Zemun. Animals were given free access to food and fluid
(water or fresh celery or parsley root or leaf juices). The average dose of doxorubicin was selected on
the basis of common human dosages and Clark's formula.
In the first part of the experiments animals were treated with doxorubicin, celery root and leaf
juices and their combination. Experimental animals were divided into six experimental groups, each
comprising six animals. Animals from the control group (CON) only drank water ad libitum; animals
from group CR drank only celery root juice instead of water; group CL was given only celery leaf
juice; animals from group CRD exclusively drank celery root juice and received doxorubicin (1.5
mg/kg) intraperitoneally (i.p.) four times in 14 days (on days 1, 5, 9, 13); group CLD drank only celery
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leaf juice and was treated with doxorubicin (1.5 mg/kg i.p.) on days 1, 5, 9, 13; group D drank water
and received doxorubicin (1.5 mg/kg i.p.) on days 1, 5, 9, 13. In the second part of the experiment the
same procedure was repeated with parsley root and leaf juices instead of celery juices. Animals from
the control group (CON) drank only water ad libitum; animals from group PR drank only parsley root
juice instead of water; group PL was given only parsley leaf juice; animals from group PRD exclusively
drank parsley root juice and received doxorubicin (1.5 mg/kg) intraperitoneally (i.p.) four times in 14
days (on days 1, 5, 9, 13); group (PLD) drank only parsley leaf juice and was treated with doxorubicin
(1.5 mg/kg i.p.) on days 1, 5, 9, 13; group (D) drank water and received doxorubicin (1.5 mg/kg i.p.) on
days 1, 5, 9, 13. Non-doxorubicin treated groups received 0.9% sodium chloride (1 mL/kg body
weight) intraperitoneally every four days instead of doxorubicin. Intervals between two concomitant
applications of doxorubicin resemble the most frequent treatment schedule used in human medicine.
On the day 17 (3 days after the last dose of doxorubicin) all animals were sacrificed under urethane
anesthesia. Blood samples were collected and livers were removed and homogenized.
3.3. Biochemical Assays
Total antioxidant status was measured in blood hemolysate and liver homogenate. Liver was
homogenized in a Potter homogenizer with 50 mM TRIS-HCl, 250 mM sucrose in ratio 1:3 at 4
o
C.
Obtained homogenate was filtered. The content of reduced glutathione (GSH) was determined in blood
after Beuthler et al. [24] and in the liver after Kapetanovic and Mieyal [25]. The total protein content
in liver was determined after Gornall et al. [26]. Total content of cytochome P-450 in rat liver
homogenate was determined after Matsubara et al. [27].
The ferric reducing antioxidant power (FRAP) assay [28] measures antioxidant power with the help
of a redox reaction, whereby ferric (Fe
3+
) to ferrous ion reduction at low pH causes the formation of a
coloured ferrous–tripyridyltriazine complex. FRAP values are obtained by comparing the absorbance
change at 593 nm in test reaction mixtures with those containing ferrous ions in known concentration.
In the FRAP assay, reductants (‘antioxidants’) in the sample reduce the Fe(III)/tripyridyltriazine
complex, present in stoichiometric excess, to the blue ferrous form, with an increase in absorbance at
593 nm. Ethanolic solutions of known FeSO
4
concentration, in the range of 20-500 µM, were used for
obtaining the calibration curve. The FRAP value was defined as the concentration of antioxidant
having a ferric reducing ability equivalent to that of 1 µM FeSO
4
. The change in absorbance is
proportional to the combined (total) ferric reducing/antioxidant power (FRAP value) of the
antioxidants in the sample.
3.4. Chemicals
2,4,6-Tripyridyl-s-triazine (TPTZ) was obtained from BDH Chemicals Ltd (Poole, England).
Doxorubicin was obtained from Pharmacia & Upjohn Inc (New Haven, CT, USA). 5,5'-Dithiobis (2-
nitrobenzoic acid (DTNB) was obtained from Merck (Darmstadt, Germany). All chemicals used were of
analytical grade.
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3.5. Statistical Analysis
Results of biochemical analyses are presented as the mean value ± standard deviation (SD). The
difference between control and test groups was analyzed using the Student t-test (significant difference
at p 0.05 confidence level).
4. Conclusions
On the basis of the obtained results we can conclude that doxorubicin decreased the content of
reduced glutathione and antioxidative status in blood hemolysate and liver homogenate but did not
have any effect on the content of cytochrome P450.
Celery root juice increased antioxidative capacity i.e. reduced glutathione content [3] and the total
antioxidative capacity (FRAP) in liver homogenate. Celery leaf juice increased GSH content [3], but
did not influence FRAP in liver homogenate.
Celery root and leaf juices in combination with doxorubicin had protective effects, i.e. they
increased the total antioxidative capacity (FRAP) in liver homogenate compared to animals treated
with doxorubicin alone.
Parsley root and leaf juices in combination with doxorubicin increased the content of reduced
glutathione in liver homogenate compared to doxorubicin treatment, suggesting possible protective
effects.
All other treatments with celery and parsley juices, alone or in combination with doxorubicin
reduced the total antioxidative status in both blood hemolysate and in liver homogenate. This could be
explained by the fact that flavonoids and other classes of plant antioxidants can act as prooxidants
under certain conditions. Further research using other more precise methods for determination of total
antioxidative activity is needed to explain the obtained results.
Recent investigations have shown that content of cytochrome P450 can be used as a marker of
oxidative stress. Parsley roots and leaves juice in combination with doxorubicin had opposite effect on
the content of Cyt P450 compared to doxorubicin.
In vivo investigations are very complex. Results are not easily explained since some components of
parsley and celery juices act as antioxidants, but also as prooxidants. Our further investigation is aimed
towards explanation of effects of celery and parsley juices on antioxidant systems.
Acknowledgements
The Ministry of Sciences and Environmental Protection, Republic of Serbia, supported this
research. We are grateful to Dr Goran Anackov who determined the plants used in this investigation.
References and Notes
1. Tokarska-Schlattner, M.; Wallimann, T.; Schlattner, U. Alterations in myocardial energy
metabolism induced by the anti-cancer drug doxorubicin. C. R. Biol. 2006, 329, 657-668.
Molecules 2010, 15
6203
2. Popovic, M.; Kaurinovic, B.; Jakovljevic, V.; Mimica-Dukic, N.; Bursac, M. Effect of parsley
(Petroselinum crispum (Mill.) Nym. ex A.W. Hill, Apiaceae) extracts on some biochemical
parameters of oxidative stress in mice treated with CCl
4
. Phytother. Res. 2007, 21, 717-723.
3. Kolarovic, J.; Popovic, M.; Mikov, M.; Mitic, R.; Gvozdenovic, Lj. Protective effects of celery
juice in treatments with doxorubicin. Molecules 2009, 14, 1627-1638.
4. Liu, T.J.; Yeh, Y.C.; Ting, C.T.; Lee, W.L.; Wang, L.C.; Lee, H.W.; Wang, K.Y.; Lai, H.C.; Lai,
H.C. Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and
neonatal cardiomyocytes. Cardiovasc. Res. 2008, 80, 227-235.
5. Wattanapitayakul, S.K.; Chularojmontri, L.; Herunsalee, A.; Charuchongkolwongse, S.;
Niumsakul, S.; Bauer, J.A. Screening of antioxidants from medicinal plants for cardioprotective
effect against doxorubicin toxicity. Basic. Clin. Pharmacol. Toxicol. 2005, 96, 80-87.
6. Lombaert, G.A.; Siemens, K.H.; Pellaers, P.; Mankotia, M. Ng W. Furanocoumarins in celery and
parsnips: method and multiyear Canadian survey. J. AOAC Int. 2001, 84, 1135-1143.``
7. Mimica-Dukić, N.; Popović, M. Apiaceae Species. A promising sources of pharmacologically
active compounds and Petrosellinum crispum, Apium greveolens and Pastinaca sativa. In Recent
Progress in Medicinal Plant Species; Govil, J.N., Singh, V.K., Eds.; Phytopharmacology and
Therapeutic Values III, LLC: Houston, TX, USA, 2007; Volume 21, pp. 132-133.
8. Fejes, S.; Blazovics, A.; Lemberkovics, E.; Petri, G.; Szoke, E.; Kery, A. Free radical scavenging
and membrane protective effects of methanol extracts from Anthriscus cerefolium L. (Hoffm.) and
Petroselinum crispum (Mill.) Nym. ex A. W. Hill. Phytother. Res. 2000, 14, 362-365.
9. Barnes, J.; Anderson, A.L.; Phillipson, J.D. Herbal Medicines; Barnes, J., Anderson, A.L.,
Phillipson, J.D., Eds; Pharmaceutical Press: London, UK, 2002; p.118.
10. Zheng, J.; Zhou, H.H. Effects of the flavonoids on cytochrome P-450 CYP1, 2E1, 3A4 and 19.
Acta Pharmacol. Sin. 2007, 42, 8-12.
11. Kaurinović, B.; Popović, M.; Ćebović, T.; Mimica-Dukić, N. Effects of Calendula officinalis L.
and Taraxacum officinale Weber (Asteraceae) extracts on the production of OH
radicals.
Fresenius Environ. Bull. 2003, 12, 250-253.
12. Ćebović, T.; Spasić, S.; Popović, M.; Borota, J.; Leposavić, G. The European Mistletoe (Viscum
Album L.) grown on plums extract inhibits CCl
4
-induced liver damage in rats. Fresenius Environ.
Bull. 2006, 15, 393-400.
13. Lakhanpal, P. ; Rai, D. K. Quercetin: A versatile flavonoid. Int. J. Med. 2007, 2, 20-35.
14. Popovic, M.; Kaurinovic, B.; Trivic, S.; Mimica-Dukic, N.; Bursac, M. Effect of celery (Apium
graveolens) extracts on some biochemical parameters of oxidative stress in mice treated with
carbon tetrachloride. Phytother. Res. 2006, 20, 531-537.
15. Pinmai, K.; Chunlaratthanabhorn, S.; Ngamkitidechakul, C.; Soonthornchareon, N.;
Hahnvajanawong, C. Synergistic growth inhibitory effects of Phyllanthus emblica and Terminalia
bellirica extracts with conventional cytotoxic agents doxorubicin and cisplatin against human
hepatocellular carcinoma and lung cancer cells. World J. Gastroenterol. 2008, 14, 1491-1497.
16. Kaneez, F.S.; Al Salam, S.; Alaaeldin, A.H. Sesame oil as a protective agent against doxorubicin
induced cardio toxicity in rat. Am. J. Pharm. Toxicol. 2007, 2, 59-163
17. Guengerich, F.P. Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J.
2006, 8, E101-E111.
Molecules 2010, 15
6204
18. Sugiyama, T.; Sadzuka, Y.; Tanaka, K.; Sonobe, T. Inhibition of glutamate transporter by
theanine enhances the therapeutic efficacy of doxorubicin. Toxicol. Lett. 2001, 121, 89-96.
19. Kamath, A.; Wang, L.; Das, H.; Li, L.; Reinhold, V.; Bukowski, J. Antigens in tea-beverage prime
human Vgamma 2Vdelta 2 T cells in vitro and in vivo for memory and nonmemory antibacterial
cytokine responses. Proc. Natl. Acad. Sci. USA 2003, 100, 6009-6014.
20. Chan, T.; Galati, G.; O'Brien, P. J. Oxygen activation during peroxidase catalysed metabolism of
flavones or flavanones. Chem. Biol. Interact. 1999, 122,15-25.
21. Muchuweti, M.; Kativu, E.; Mupure, C.H.; Chidewe, C.; Ndhlala, A.R.; Benhura, M.A.N.
Phenolic composition and antioxidant properties of some spices. Am. J. Food Technol. 2007, 2,
414-420.
22. Lin, Y.; Shi, R.; Wang, X.; Shen, H.M. Luteolin, a flavonoid with potentials for cancer prevention
and therapy. Curr. Cancer Drug Targets 2008, 8, 634-646.
23. Křížková, J.; Burdová, K.; Stiborová, M.; Křen, V.; Hodek, P. The effects of selected flavonoids
on cytochromes P450 in rat liver and small intestine. Interdisc Toxicol. 2009, 2, 201-204.
24. Beuthler, E.; Duron, O.; Kelly, B. Improved methods for the determination of blood glutathione.
J. Lab. Clin. Med. 1983, 61, 882-889.
25. Kapetanović, I.M.; Mieyal, I.I. Inhibition of acetaminophen induced hepatotoxicity by phenacetin
and its alkoxy analogs. J. Pharmacol. Exp. Ther. 1979, 209, 25-30.
26. Gornall, H.G.; Nardwall, C.L. Estimation of total protein in tissue homogenate. J. Biol. Chem.
1949, 177, 751-756.
27. Matsubara, T.; Koike, M.; Touchi, A.; Tochino, Y.; Sugeno, K. Quantitative determination of
cytochome P-450 in rat liver homogenate. Anal. Biochem. 1976, 75, 596-603.
28. Benzie, I.F.F.; Strain, J.J. Methods in Enzymology; Packer, L., Ed.; Academic Press Orlando: New
York, NY, USA, 1999; Volume 299, pp. 15-27.
Sample Availability: Samples of the compounds are available from the authors.
© 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an Open Access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).
... Kolarovic et al. investigated the antioxidant activity of celery in rats treated with doxorubicin and also the effect of the celery itself, and its combination with doxorubicin was determined by its antioxidant status [160]. The n-butanol extract from A. graveolens seed at 60 mg/kg ameliorate lipid peroxidation and its antioxidant properties improved antioxidant enzymes in streptozotocin-induced diabetic rats after 21 days of treatment [26]. ...
... We also note that these studies have mostly been conducted on A. graveolens species, but sometimes, other Apium species have been examined. Generally, Apium plants can prevent cardiovascular diseases, jaundice, liver and lien diseases, urinary tract obstruction, gout, and rheumatic disorders [160]. ...
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Apium plants belong to the Apiaceae family and are included among plants that have been in use in traditional medicine for thousands of years worldwide, including in the Mediterranean, as well as the tropical and subtropical regions of Asia and Africa. Some highlighted medical benefits include prevention of coronary and vascular diseases. Their phytochemical constituents consist of bergapten, Appl. Sci. 2019, 9, 3547 2 of 39 induction. The present review summarizes data on ecology, botany, cultivation, habitat, medicinal use, phytochemical composition, preclinical and clinical pharmacological efficacy of Apium plants and provides future direction on how to take full advantage of Apium plants for the optimal benefit to mankind.
... A study was conducted to assess the antioxidant activity in celery using aqueous extract from leaves and roots. Results showed that leaves and roots exhibited antioxidant activity resulting in reduced glutathione content whereas n-Butanol extract of celery seeds showed antioxidant activity showed enhanced body weight (Kolarovic et al., 2010;Al Saaidi et al., 2012). Ethanolic extract from celery leaves found to exhibit scavenging activity on malondialdehyde (MDA) and lipofuscin (LPF), promote total antioxidant capacity (TOAC) and enhanced activity of superoxide dismutase (SOD) (Li et al., 2014). ...
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Celery, a member of the Apiaceae family, is an important medicinal herb. It is rich in bioactive compounds and its importance is increasing among the health-conscious crowd these days. Celery, as an edible crop, finds use in both raw and processed form. Extracts obtained from different parts of the plant viz., leaves, stalk, roots and seeds possess several medicinal properties. Specifically, these extracts are found to have antimicrobial, antioxidant, anti-cancerous, anti-adhesive and anti-inflammatory properties, along with the ability to lower serum lipid levels. Availability of genomic resources is limited in celery, for which the molecular study of the crop becomes tedious. Unravelling the genetic cause behind various physiological and biochemical changes thus, becomes difficult. Though scanty, the available genomic information of celery has paved the way for advancement of several breeding lines. Comparative and functional genomics have untangled several genes which are known for regulating several adaptive and agronomic traits in celery. Though achievements have been reported in the genetics, breeding, genomic resources and molecular research of celery, in-depth examination should be conducted for unravelling the genetic variations, phenotypic variations, and characterization of novel alleles for agronomically important genes. Current review summarizes the recent advances in the genetics, genomics, breeding, chemical composition and biochemistry of the crop.
... However, Pokluda [23] suggested that the nitrate content of 15 root parsley cultivars was within tolerance limits. Moreover, in the study by Kolarovic et al. [24], it was suggested that parsley root juice might show protective effects against doxorubicin-induced cardiotoxicity. Crop diversification in the Mediterranean basin, through the introduction of new species and/or cultivars of conventional crops, is imminent due to the severe effects of climate change and the increasing need for genotypes better adapted to the new conditions [25]. ...
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... Restoration of the disturbed enzyme activities and hepatic architecture with the correction of metabolic product concentrations after PSM supplementation is the primary explanation for their hepatoprotective effects. Indeed, the hepatoprotective effect of parsley arises from its capacity to scavenge ROS, as reported in numerous assays [95,96]. The decreased LDH and hypocholesterolemia due to the concurrent treatment with 20% parsley seed methanol extract was documented in rats [97]. ...
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... Regarding the effect on liver function, in the present work, SGOT and SGPT significantly reduced during 4-week celery treatment (p < 0.05) while ALP had no change after celery administration (p > 0.05). Celery stimulates the healthy and normal functioning of the liver (Kolarovic et al. 2010). Celery root and leaf juices enhance antioxidative capacity i.e. decrease glutathione content and the antioxidative capacity in liver homogenate (Kolarovic et al. 2009). ...
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The in vitro and in vivo antioxidant activity of different extracts of leaves and root of parsley (Petroselinum crispum (Mill.) Nym. ex A.W. Hill, Apiaceae) were studied. Free radical scavenging capacity (RSC) was evaluated measuring the scavenging activity on the 2,2-diphenyl-1-picrylhydrazil (DPPH) and OH radicals. Also, the effects on lipid peroxidation (LP) were evaluated. The results obtained showed that all examined extracts act as good scavengers of DPPH and OH radicals and reduce the intensity of LP. The in vivo effects were evaluated on some antioxidant systems (activities of LPx, GSH-Px, Px, CAT and XOD, and GSH content) in the mice liver and blood after treatment with the examined parsley extracts, or in combination with carbon tetrachloride (CCl(4)). On the basis of the results obtained it can be concluded that the examined extracts exhibited a certain protective effect. However, combined treatments with CCl(4) and the examined extracts showed both positive and negative synergism, inducing or suppressing the influence of CCl(4) alone.