Pharmacological Research 51 (2005) 117–123

Quercetin, a flavonoid antioxidant, prevents and protects

streptozotocin-induced oxidative stress and ␤-cell
damage in rat pancreas
Omer Coskun a,∗ , Mehmet Kanter a , Ahmet Korkmaz b , Sukru Oter b
a Department of Medical Histology and Embryology, Zonguldak Karaelmas University, Faculty of Medicine, Zonguldak, Turkey
b Department of Physiology, Gulhane Military Medical Academy, Ankara, Turkey

Accepted 4 June 2004

Abstract

The aim of the present study was the evaluation of possible protective effects of quercetin (QE) against ␤-cell damage in experimental
streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg kg−1 for diabetes induction. QE
(15 mg kg−1 day, intraperitoneal (i.p.) injection) was injected for 3 days prior to STZ administration; these injections were continued to the
end of the study (for 4 weeks). It has been believed that oxidative stress plays a role in the pathogenesis of diabetes mellitus (DM). In order
to determine the changes of cellular antioxidant defense system, antioxidant enzymes such as glutathione peroxidase (GSHPx), superoxide
dismutase (SOD) and catalase (CAT) activities were measured in pancreatic homogenates. Moreover we also measured serum nitric oxide
(NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, if there is an imbalance between
oxidant and antioxidant status. Pancreatic ␤-cells were examined by immunohistochemical methods. STZ induced a significant increase
lipid peroxidation, serum NO concentrations and decreased the antioxidant enzyme activity. Erythrocyte MDA, serum NO and pancreatic
tissue MDA significantly increased (P < 0.05) and also the antioxidant levels significantly decreased (P < 0.05) in diabetic group. QE
treatment significantly decreased the elevated MDA and NO (P < 0.05), and also increased the antioxidant enzyme activities (P < 0.05). QE
treatment has shown protective effect possibly through decreasing lipid peroxidation, NO production and increasing antioxidant enzyme
activity. Islet cells degeneration and weak insulin immunohistochemical staining was observed in STZ induced diabetic rats. Increased
staining of insulin and preservation of islet cells were apparent in the QE-treated diabetic rats.
These findings suggest that QE treatment has protective effect in diabetes by decreasing oxidative stress and preservation of pancreatic
␤-cell integrity.
© 2004 Elsevier Ltd. All rights reserved.

Keywords: Quercetin; Diabetes; Streptozotocin; Oxidative stress

1. Introduction
Diabetes mellitus (DM) is a pathologic condition, re-
sulting in severe metabolic imbalances and non-physiologic
changes in many tissues, where oxidative stress plays an
important role in the etiology [1]. Ihara et al. [2] examined
oxidative stress markers in diabetic rats and found increased
reactive oxygen species (ROS) in pancreatic islets. Diabet-
ics and experimental animal models exhibit high oxidative
stress due to persistent and chronic hyperglycemia, thereby
deplete the activity of the antioxidative defense system and
∗ Corresponding author. Tel.: +90 372 2577394; fax: +90 372 2577395.
E-mail address: omercoskun1970@hotmail.com (O. Coskun).
thus promote free radical generation [1]. Such models in-
clude alloxan or streptozotocin (STZ) induced diabetic rats
and mice.
STZ, an antibiotic produced by Streptomyces achromo-
genes, is a common used agent in experimental diabetes [3].
In STZ induced type 1 diabetes, hyperglycemia and oxida-
tive stress have been implicated in the etiology and pathol-
ogy of disease complications [1]. The mechanism by which
STZ destroys ␤-cells of the pancreas and induces hyper-
glycemia is still unclear. One of the actions which have been
attributed to STZ is depletion of intracellular nicotineamide
dinucleotide (NAD) in islet cells [4]. In addition, STZ has
been shown to induce DNA strand breaks and methylation in
pancreatic islet cells [5]. Chemicals with antioxidant prop-
erties and free radical scavengers were shown to prevent

1043-6618/$ – see front matter © 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.phrs.2004.06.002
118 O. Coskun et al. / Pharmacological Research 51 (2005) 117–123
pancreatic islets against cytotoxic effects of STZ or alloxan,
another agent inducing experimental diabetes [6].
Flavonoids are a group of naturally occurring compounds
widely distributed as secondary metabolites in the plant
kingdom. They have been recognized for having interest-
ing clinical properties, such as anti-inflammatory, antialler-
gic, antiviral, antibacterial, and antitumoral activities [7].
One of these flavonoids, quercetin (QE) (3,5,7,3 ,4 -pentahy-
droxyflavone), prevents oxidant injury and cell death by
several mechanisms, such as scavenging oxygen radicals
[8,9] protecting against lipid peroxidation [10] and chelating
metal ions [11].
The cellular antioxidant status determines the suscep-
tibility to oxidative damage and is usually altered in re-
sponse to oxidative stres. Accordingly, interest has recently
grown in the role and usage of natural antioxidants as a
means to prevent oxidative damage in diabetes with high
oxidative stress. The antioxidants such as Vitamins C and
E, enzymes superoxide dismutase (SOD), catalase (CAT),
glutathione peroxidase (GSHPx) have been shown to pro-
tect the cells against lipid peroxidation, the initial step of
many pathological processes [12,13]. Reduced antioxidant
levels as a result of increased free radical production in ex-
perimental diabetes have been reported by many authors
[14,15].
The present study was undertaken to determine whether
the pancreas was subjected to oxidative damage during
experimental diabetes as well as to examine the accom-
panying changes in antioxidant status. In addition, we
explored whether QE treatment protects pancreatic ␤-cells
against STZ damage in rats, by immunohistochemical
staining.
2. Materials and methods
2.1. Treatment of rats
Thirty healthy male Wistar albino rats, weighing 200–
250 g, and averaging 16 weeks old were utilized in this study.
They were housed in macrolon cages under standard labo-
ratory conditions (light period 7.00 a.m. to 7.00 p.m., 21 ±
2 ◦ C, relative humidity 55%). The animals were given stan-
dard rat pellets (Murat animal food product Co., Ankara,
Turkey) and tap water ad libitum. The rats were randomly
allotted into three experimental groups: A (control), B (di-
abetic) and C (QE-pretreated diabetic), each containing 10
animals. In groups B and C, diabetes was induced by a sin-
gle intraperitoneal (i.p.) injection of STZ (Sigma, St. Louis,
MO, USA), with a dose of 50 mg kg−1 body weight, freshly
dissolved in 5 mmol l−1 citrate buffer (pH 4.5) [16,17]. Con-
trol group was injected with the same volume of isotonic
NaCl as the diabetic groups received. In group C, daily QE
(Sigma, St. Louis, MO, USA) injections were began 3 days
prior to induction of diabetes (15 mg kg−1 day, i.p.). QE was
dissolved in 0.5 ml of 60% ethanol just before injection and
these procedure were continued until the end of the study,
for 4 weeks. The dose of QE was chosen on the basis of
a previous study [18]. All animals received human care ac-
cording to the criteria outlined in the “Guide for the Care
and Use of Laboratory Animals” prepared by the National
Academy of Sciences and published by the National Insti-
tutes of Health.
2.2. Biochemical analysis
Two days after STZ treatment, development of diabetes
was confirmed by measuring blood glucose levels in blood
samples taken from tail vein. Rats with blood glucose levels
of 250 mg dl−1 or higher were considered to be diabetic.
Diabetes was observed in 20 of 28 rats, and 20 randomly
selected of these rats were used in this experiment as
group B and C. Plasma glucose levels in control animals
remained normal for the duration of the study. Glucose
measurement was made with Ames One Touch Glucome-
ter (LifeScan, Johnson and Johnson, New Brunswick,
NJ, USA).
At the end of the experiment rats in all groups were
fasted overnight for 12 h, and sacrificed under chloralhy-
drate (Sigma, St. Louis, MO, USA) anaesthesia (6 ml of
7% chloralhydrate kg). Blood samples were collected by
cardiac puncture using heparinised syringe. Serum glucose
was determined by hexokinase method with reagents from
Boehringer (Mannheim, FR, Germany), and insulin was
determined with a double-antibody radioimmunoassay kit
(Amersham Radiochemical Centre, Bucks, UK).
Blood malondialdehyde (MDA) (mmol l−1 ) was deter-
mined by the double heating method of Draper and Hadley
[19]. Harvested pancreas tissues were washed with distilled
water prior to homogenisation to remove residual blood.
The tissues were homogenised in buffers by means of Ultra
Turrax T25 homogenisator. The soluble fraction was pre-
pared by centrifugation at 6000 × g for 10 min. The prin-
ciple of the method is spectrophotometric measurement of
the color produced during the reaction to thiobarbituric acid
(TBA) with MDA. For this purpose, 2.5 ml of 100 g l−1
trichloroacetic acid solution was added to 0.5 ml erythrocyte
in each centrifuge tube and placed in a boiling water bath
for 15 min. After cooling in tap water, the mixture was cen-
trifuged at 1000 × g for 10 min, and 2 ml of the supernatant
was added to 1 ml of 6.7 g l−1 TBA solution in a test tube
and placed in a boiling water bath for 15 min. The solution
was then cooled in tap water and its absorbance was mea-
sured using a Shimadzu UV-1601 (Japan) spectrophotome-
ter at 532 nm. The concentration of MDA was calculated by
the absorbance coefficient of MDA-TBA complex 1.56 ×
105 cm−1 M−1 , and was expressed in ␮mol g−1 Hb erythro-
cyte and ␮mol g−1 tissue protein. Tissue SOD and GSH-Px
activities were measured by using Ransod and Ransel (Ran-
dox Laboratories GmbH, Deutschland) commercial kits, re-
spectively with the Shimadzu UV-1601 spectrophotometer.
Tissue CAT activity was determined according to Aebi’s
 O. Coskun et al. / Pharmacological Research 51 (2005) 117–123 119

method [20]. Protein measurements were made according to performed these measurements was unaware of the experi-
Lowry’s method [21]. NO production (␮mol l−1 ) was mea- ment.
sured indirectly using a quantitative, colorimetric assay [22]
based on the Griess reaction. 2.6. Statistical analysis

2.3. Histopathological procedures
Pancreatic tissues were harvested from the sacrificed an-
imals, and the fragments from tissues were fixed in 10%
neutral formalin solution, embedded in paraffin and then,
stained with haematoxylin and eosin.
2.4. Immunohistochemical procedures
The data were expressed as mean ± standard deviation
(S.D.) and analysed using repeated measures of variance.
Tukey test was used to test for differences among means
when ANOVA indicated a significant (P < 0.05) and (P <
0.001). For the analysis of the immunohistochemical data, a
nonparametric test (Kruskal–Wallis) was used. Differences
were considered statistically significant if P < 0.05.

Harvested pancreatic tissues fixed in 10% neutral buffered 3. Results

formalin, were embedded in paraffin and sectioned at 5 ␮m
thickness. Immunocytochemical reactions were performed Body weight, blood glucose levels and serum insulin lev-
using the ABC technique according to Hsu et al. [23]. Spe- els of animals are shown in Table 1. The baseline weight
cific monoclonal mouse antisera against human insulin pro- of the rats at the beginning of the study was similar in all
tein (Zymed 18-0066, USA) were applied at a dilution of groups. At the end of the treatment (after 4 weeks), diabetic
1:50. The procedure was performed by the following steps: animals presented weight loss, but body weight differed not
(1) inhibition of endogenous peroxidase activity was inhib- in control and QE-treated diabetic rats.
ited with 3% H2 O2 in distilled water for 30 min; (2) washed
in tap water for 30 min and in distilled water for 10 min; 3.1. Biochemical findings
(3) blocked of non-specific binding of antibodies by incu-
bation with normal goat serum (DAKO X 0907) with PBS, The diabetic animals exhibited consistently hyper-
diluted 1:4; (4) incubation with monoclonal mouse antisera glycemia. QE treatment caused a decrease in the elevated
against human insulin protein, diluted 1:400 for 2 h, then at serum glucose (P < 0.001) and an increase in the lowered
room temperature; (5) washed in PBS 6 min; (6) incubation serum insulin (P < 0.001) levels in STZ-diabetic rats, as
with biotinylated anti-mouse IgG (DAKO LSAB 2 Kit; (7) measured at the end of study.
washed in PBS 9 min; (8) incubation with ABC complex Erythrocyte MDA, serum NO and pancreatic tissue MDA,
(DAKO LSAB 2 Kit); (9) washed in PBS 6 min; (10) per- SOD, GSH-Px and CAT levels were presented in Table 2.
oxidase detection using AEC; (11) washed in tap water for Erythrocyte MDA, serum NO and pancreatic tissue MDA
10 min, dehydration; (12) nuclei stained with hematoxylin; significantly increased (P < 0.05) and also the antioxidant
and (13) sections mounted in DAKO faramount. Prepara- levels significantly decreased (P < 0.05) in diabetic group.
tions were evaluated by a bright field microscope and were QE treatment significantly decreased the elevated MDA and
photographed (Nikon Optiphot 2, Tokyo). NO (P < 0.05), and also increased the reduced antioxidant
Ten Langerhans islets from each rat, thus 100 islets for enzyme activities (P < 0.05).
each group, were chosen randomly. The intensity of staining
with antiinsulin antibodies was scored semiquantitatively as Table 1
0 (absent), 1 (weak), 2 (moderate), 3 (strong) and 4 (very Body weight, serum glucose levels and serum insulin levels of A (control),
B (diabetic) and C (QE-pretreated diabetic) groups
strong).
Parameters n A B C
2.5. Image analysis Initial body weight (g) 10 226 ± 12 228 ± 8 224 ± 6
Final body weight (g) 10 228 ± 7 201 ± 7a 231 ±
The system used is composed of a PC, hardware and Initial serum glucose 10 104 ± 4 102 ± 8 103 ± 6
software (Image-Pro Plus 5.0-Media Cybernetics, USA) for (mg dl−1 )
Final serum glucose 10 97 ± 6 334 ± 11b 132 ± 14c
image acquisition and analysis, Spot Insight QE (Diagnos- (mg dl−1 )
tic Instruments, USA) camera and optical microscope. The Initial serum insulin 10 57 ± 5 58 ± 4 59 ± 5
method requires preliminary software procedures of spatial (mU l−1 )
calibration (micron scale) and setting of color segmentation Final serum insulin 10 53 ± 4 15 ± 2b 38 ± 4c
for quantitative color analysis. Fifty Langerhans islets from (mU l−1 )
each group were chosen randomly. The area of insulin im- Statistical analysis was by a one-way ANOVA with Tukey’s test. Values
are expressed as mean ± S.D., and n = 10 for all groups.
munoreactive ␤-cells in the Langerhans islets was measured. a P < 0.05 when compared with group A and C.
The percentage of the insulin immunoreactive ␤-cells was b P < 0.001 when compared with group A.
calculated according to these results. The investigator who c P < 0.05 when compared with group A and B.
120 O. Coskun et al. / Pharmacological Research 51 (2005) 117–123

Fig. 1. Control group: showing normal cells in the islet of Langerhans and also showing ␤-cells in the islet of Langerhans that are strong staining with
the anti-insulin anti-body. Immunoperoxidase, haematoxylin counterstain × 420.

Fig. 2. Diabetic group: shrunken islets of Langerhans displaying degenerative and necrotic changes in diabetic rats with no treatment, and that are weak
insulin-immunoreactivity in a few ␤-cells in the islet of Langerhans. Immunoperoxidase, haematoxylin counterstain × 420.

3.2. Histological findings
The histology of pancreatic islet cells was normal in con-
trol group. In immunohistochemical staining of the pancre-
atic tissues in control group was observed strong insulin
antigen positivity in the ␤–cells of the islets (Fig. 1). In di-
abetic rats with no treatment, the most consistent findings
in the histologic sections of pancreatic tissues stained with
haematoxylin and eosin were the degenerative and necrotic
changes, and shrunken in the islets of Langerhans. The nu-
cleus of necrotic cells indicated either pyknosis or marginal
hyperchromasie. There was mostly hydropic degeneration
and degranulation in the cytoplasm of the degenerative and
necrotic cells, while some of the cells with pyknotic nucleus
had a dark eosinophilic cytoplasm. Immunohistochemical
staining of the pancreatic tissues in diabetic rats represented
weak insulin-immunoreactivity in a few ␤-cells in the islet of
Langerhans (Fig. 2). QE treatment protected the majority of
cells of Langerhans islet. Nevertheless, in the remaining cells
were observed light hydropic degeneration, degranulation
 O. Coskun et al. / Pharmacological Research 51 (2005) 117–123 121

Fig. 3. QE-treated group: NS has protected the majority of beta-cells in the islet of Langerhans and shown moderate staining with the anti-insulin
antibody. Immunoperoxidase, haematoxylin counterstain × 420.

Table 2 Table 4
Erythrocyte MDA (␮mol g−1 Hb), serum NO (␮mol l−1 ) and pancreatic Comparison area of the insulin immunoreactive ␤-cells in the Langerhans
tissue MDA (␮mol g−1 protein), SOD (U mg−1 protein), GSH-Px (U mg−1 A (control), B (diabetic) and C (QE-pretreated diabetic) groups
protein) and CAT (k mg−1 protein) levels of all groups
Groups Mean area of insulin immunoreactive
Parameters A B C ␤-cells in islets

Erythrocyte MDA 8.92 ± 1.07 15.23 ± 2.03a 11.48 ± 1.24b A 86.74 ± 1.92%
Tissue MDA 94 ± 11 134 ± 22a 108 ± 14b B 4.68 ± 0.21%a
Serum NO 4.12 ± 0.68 7.42 ± 1.22a 4.76 ± 0.84c C 47.34 ± 1.24%b
Tissue SOD 22.88 ± 9.61 12.42 ± 1.32a 16.08 ± 2.24b Kruskal–Wallis test was used for statistical analysis. Values are expressed
Tissue GSH-Px 0.37 ± 0.03 0.23 ± 0.03a 0.30 ± 0.03b as mean ± S.D., and n = 10 animals for all groups.
Tissue CAT 0.34 ± 0.02 0.21 ± 0.02a 0.26 ± 0.02b a P<0.001 when compared with group A.
b P<0.001 when compared with group A and B.
A (control), B (diabetic) and C (QE-pretreated diabetic) groups. Statistical
analysis was by a one-way ANOVA with Tukey’s test. Values are expressed
as mean ± S.D., and n = 10 for all groups. islets of Langerhans (Fig. 3). The semi-quantitative analy-
a P < 0.05 when compared with group A.
b P < 0.05 when compared with group A and B.
sis of immunohistochemical staining is shown in Table 3.
c P < 0.05 when compared with group B. The area of insulin immunoreactive ␤-cells in the Langer-
hans islets was measured. The percentage of the insulin
immunoreactive ␤-cells was calculated according to these
and necrosis. In addition, a few cells with picnotic nucleus results showed in Table 4. STZ induced a significant de-
were indicated. In immunohistochemical staining of the pan- crease the area of insulin immunoreactive ␤-cells. QE treat-
creatic tissues in diabetic QE-treated rats there was moder- ment increased the area of insulin immunoreactive ␤-cells
ate insulin antigen positivity in the majority of ␤-cells of the significantly.

Table 3
Semi-quantitative analysis of immunohistochemical staining of insulin in ␤-cells in pancreatic islets of control rats (A), diabetic rats (B) and QE-pretreated
diabetic (C) groups
Groups n 1 (Weak) 2 (Moderate) 3 (Strong) 4 (Very strong)

A 100 – – – 100
Ba 100 84 26 – –
Cb 100 – 40 40 20
Kruskal–Wallis test was used for statistical analysis. Values are expressed as mean ± S.D., and n = 100 islets for all groups.
a P < 0.05 when compared with group A.
b P < 0.05 when compared with group B.
122 O. Coskun et al. / Pharmacological Research 51 (2005) 117–123
4. Discussion
The possible sources of oxidative stress in the patho-
genesis of diabetes and diabetic complications have been
extensively studied for years based on in animal models
and in patients. Diabetics and experimental animal models
exhibit high oxidative stress due to persistent and chronic
hyperglycemia, which thereby depletes the activity of an-
tioxidative defense system and thus promotes de novo free
radicals generation [1,2]. Numerous studies have found in-
creased lipid peroxides or ROS and oxidative stress (or both)
in different animal models of diabetes [24,25]. Oxidative
stress has recently been shown to be responsible, at least
in part, for the ␤-cell dysfunction caused by glucose toxi-
city. Under hyperglycemia, production of various reducing
sugars such as glucose-6-phosphate and fructose increases
through glycolysis and the polyol pathway. During this
process, ROS are produced and cause tissue damage [26].
In vitro and in vivo studies have suggested the implication
of oxidative stress in the progression of ␤-cell dysfunction
in type 2 diabetes, too [27].
STZ has a ␤-cell cytotoxic and a slight carcinogenic
effect. Although the ␤-cell cytotoxic action of STZ is not
fully understood, it is though to be mediated by the inhibi-
tion of free radical scavenger-enzymes thereby enhancing
the production of the superoxide radical. Eventually, STZ
causes diabetes mellitus and diabetes is associated with the
generation of ROS causing oxidative damage [28]. Srini-
vasan and Menon [29] reported that the antioxidant drug
bis-o-hydroxycinnamoylmethane used protection of ␤-cells
against ROS mediated damage by enhancing antioxidants
and reduces hyperglycemia in STZ-induced diabetes. In
the present study, we examined possible usefulness of the
potent antioxidant QE. Damaged ␤-cells often display ex-
tensive degranulation when examined histologically, and
are clinically associated with the development of diabetes.
In our study, almost all insulin-positive ␤-cells were de-
granulated, degenerated or necrosed in the STZ treated
rats leading to decrease in insulin secretion and an in-
crease in blood glucose concentration. STZ induced a
significant decrease the area of insulin immunoreactive ␤-
cells.
Quercetin, a flavonoid, used in doses of 10–50 mg kg−1
body mass was shown to be capable of normalizing blood
glucose level, augmenting liver glycogen content and signif-
icantly reducing serum cholesterol and LDL concentration
in alloxan-diabetic rats [30]. Hii and Howell [31] reported
that exposure of isolated rat islets to certain flavonoids such
as (−)-epicatechin or quercetin enhances insulin release by
44–70%. They argue that such flavonoids may act on islet
function, at least in part, via alteration in Ca2+ fluxes and
in cyclic nucleotide metabolism. Vessal et al. [18] suggested
that QE supplementation has proven to be beneficial in de-
creasing blood glucose concentration, promoting regenera-
tion of the pancreatic islets and increasing insulin release in
STZ-induced diabetic rats; thus exerting its beneficial an-
tidiabetic effects. In the literature, interest to the role and
usage of natural antioxidants for preventing oxidative dam-
age in diabetes has recently grown [11,18,30,32–34]. But
no immunohistochemical data is available about the the ef-
fects of QE on of diabetic animals. In the present study, QE
treatment caused a sharp decrease in the elevated serum glu-
cose and a slight increase in the lowered serum insulin con-
centrations in STZ-induced diabetic rats. QE treatment also
protected the majority of cells of Langerhans islet. Neverthe-
less, light hydropic degeneration, degranulation and necrosis
were observed in the remaining cells. The current immuno-
histochemical examination shows that pancreatic ␤-cells are
destroyed by STZ whereas QE partially prevents degenera-
tion of ␤-cells. QE treatment increased the area of insulin
immunoreactive ␤-cells significantly.
Quercetin, a flavonoid found in many plants, is widely
distributed in edible fruits and vegetables. When quercetin
was administered orally, it was poorly absorbed from the
digestive tract and did not have a great influence on the or-
gans [35,36]. Quercetin is the major flavonoid in the hu-
man diet and its daily intake with foods is estimated to be
50–500 mg [37]. The injected intraperitoneally of a single
dose of 15 mg kg−1 to rat is equivalent of about 1000 mg
to a (70 kg) human person. Normalization of glucose tol-
erance curves in diabetic animals treated with either 10
or 15 mg quercetin per kg body mass [18]. Plasma glu-
cose lowering effects of quercetin in STZ-induced diabetic
rats and its lack of effects on plasma glucose level of nor-
moglycemic animals is in agreement with previously re-
ported effects of (−)-epicatechin [32], and quercetin [30] in
alloxan-diabetic animals. There is no knowledge in the lit-
erature, how quercetin acts in type 1 experimental diabetes.
In our experiment, namely STZ induced experimental type 1
diabetes, we have shown that quercetin is effective not only
insulin sensitivity but also ␤-cell protection. We examined
the possible usefulness of the quercetin has a preventive and
protective effect in diabetes by decreasing oxidative stress
and preservation of pancreatic ␤-cell integrity. Such dam-
aged ␤-cells often display extensive degranulation when ex-
amined histologically, and are clinically associated with the
development of diabetes in some model animals for type
2 diabetes [2,27]. Therefore, protection of ␤-cells against
chronic hyperglycemia induced damage is an important tar-
get for the treatment of type 2 diabetes. Lipid peroxidation
may bring about protein damage and inactivation of mem-
brane bound enzymes either through direct attack by free
radicals or through chemical modification by its end prod-
ucts, such as MDA. In our study, erythrocyte and tissue MDA
and serum NO concentration was significantly increased in
diabetic group with reduction in antioxidant enzyme activ-
ities of SOD, GSHPx and CAT. QE treatment decreased
the elevated MDA and NO and also increased the reduced
antioxidant enzyme activities. Our result is consistent with
the results of Wolf [38] and El-Missiry [39], who indicated
an increase in lipid peroxides and a decrease in antioxidant
enzymes in DM. Namely, our results indicate that the pre-
 O. Coskun et al. / Pharmacological Research 51 (2005) 117–123
ventive effects of QE may be due to inhibition of lipid per-
oxidation by its antioxidant nature.
As conclusion, QE shows protective effects in experi-
mental diabetes, possibly by decreasing oxidative stress and
preservation pancreatic ␤-cell integrity. But to elucidate the
exact mechanism of this modulatory effect, and to examine
its potential therapeutic effects further studies are essential.
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