Journal of Applied Animal Research

ISSN: 0971-2119 (Print) 0974-1844 (Online) Journal homepage: http://www.tandfonline.com/loi/taar20

Effect of Lycopene Administration on Plasma

Glucose, Oxidative Stress and Body Weight in
Streptozotocin Diabetic Rats
Vesile Duzguner , Altug Kucukgul , Suat Erdogan , Sefa Celik & Kazim Sahin
To cite this article: Vesile Duzguner , Altug Kucukgul , Suat Erdogan , Sefa Celik & Kazim Sahin
(2008) Effect of Lycopene Administration on Plasma Glucose, Oxidative Stress and Body
Weight in Streptozotocin Diabetic Rats, Journal of Applied Animal Research, 33:1, 17-20, DOI:
10.1080/09712119.2008.9706888
To link to this article: http://dx.doi.org/10.1080/09712119.2008.9706888

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Published online: 14 Nov 2011.

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Date: 06 January 2016, At: 17:34

J. Appl. h i m . Res. 33 (2008) : 17-20

Effect of Lycopene Administration on Plasma Glucose,

Oxidative Stress and Body Weight in
Streptozotocin Diabetic Rats
Vesile Duzguner",Altug Kucukgul",Suat Erdogan*l,Sefa Celik", Kazim Sahin#

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*Department of Biochemistry
Faculty of Veterinary Medicine
Mustafa Kemal University
31034 Hatay, Turkey
'Department of Animal Nutrition and Nutritional Disease
Faculty of Veterinary Medicine
Firat University
Elazig, Turkey
(Received February 8,2007; accepted September 06, 2007)

Abstract
Duzguner, V., Kucukgul, A., Erdogan, S., Celik, S. and Sahin, K. 2008. Effect of lycopene administration
on plasma glucose, oxidative stress and body weight in streptozotocin diabetic rats. J. Appl. h i m . Res., 33:
17-20.

To evaluate the role of lycopene, a carotenoid antioxidant, on streptozotocin (STZ)-induced diabetic rats,
12 female rats received a single intraperitonial injection of STZ at a dose of 45 m g l k g body weight of
which 6 were given 10 mglkg lycopene orally (test group) once daily for 21 days. The administration of
S T Z caused a significant increase in plasma glucose and decrease in body weight. The supplementation
of lycopene significantly reduced diabetic plasma glucose level by 25% and prevented body weight loss
starting from 14thday of lycopene administration. Although tissue lipid peroxidation and nitric oxide (NO)
levels were unchanged, lycopene administration significantly reduced diabetes-elevated lipid peroxidation
and NO in plasma. I t was concluded that lycopene supplementation may be valuable for correcting
hyperglycemia and preventing diabetic complications caused by lipid peroxidation and free radicals.
Keywords: Diabetes, lipid peroxidation, lycopene, STZ, rat.

decline of antioxidant defence mechanisms

can lead to damage of cellular organelles and
enzymes and increased lipid peroxidation
(Maritim et al., 2003; Rajasekaran et al.,
2005).

Introduction
Diabetes mellitus is a metabolic disorder
characterized by hyperglycemia and
insufficiency of secretion o r action of
endogenous insulin (Sailaja et al., 2003). High
levels of free radicals and the simultaneous

Lycopene, an acyclic non-provitamin-A

carotenoid with 11 linearly arranged
conjugated double bonds has somewhat
higher antioxidant activity than p-carotene
but it is found in relatively few foods. It was

'Corresponding author Tel: +90-326-2455845/1538,

Fax: +9Q-326-2455704;E-mail: serdogan8mku.edu.tr

17
J. Appl. h i m . Res. 0971-2119/2008/$10.000 GSP, India.

18

V. Duzguner and coworkers

suggested t h a t lycopene intake correlated

inost closely with inhibition of low densitylipid (LDL) oxidation (Steinberg and Chait,
1998).

The aim of the present study was t o

investigate t h e effect of lycopene
supplementation on lipid peroxidation, body
weight, fasting blood glucose concentration
a n d antioxidant enzyme activity i n
streptozotocin induced diabetic rats.

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Materials and Methods

Wistar female rats (263r23 g) were kept
under standard laboratory conditions. After
overnight fasting, diabetes was induced by
intraperitoneal (ip) injection of STZ (Sigma)
dissolved in 0.1 M cold sodium citrate buffer,
pH 4.5, at a dose of 45 mgkg. The control
rats received the vehicle alone. The r a t s
were allowed to drink 5% glucose solution
overnight t o overcome the drug-induced
hypoglycemia.
Forty-eight
hours
after
STZ
administration, the glucose concentration
was measured in whoIe blood. Rats having a
glucose concentration <250 mg/dl were
excluded from the experiment. The rats were
divided into 3 groups (n=6): control (no
treatment), diabetic without treatment and
1yco p e n e - s u ppl eme n t e d diabetic group .
Plasma glucose levels were measured with
an Accu Check Go strip test in a glucometer
(Glucometer AC go, Roche Diagnostics) and
the body weight of the rats was monitored
a t days 0, 7, 14 and 21.
Lycopene (DSM Inc. Istanbul, Turkey)
were suspended i n sunflower oil a n d
administered t o animals a t the doses of 10
mg/kg once a day for 2 1 d. Control and
diabetic rats received the same volume of
sunflower oil. The rats were anesthetized by
intramuscular injection of 50 mgkg ketamine
and blood was taken by puncturing the heart
ventricle a t the end of the experiment. The
brain, kidney, liver and spleen were taken
from each r a t , washed with ice-cold

physiological saline and used for biochemical

studies.
Tissue samples were homogenized in
ice-cold PBS buffer (pH 7.0) containing
complete protease inhibitor mixture (Sigma,
Germany). Homogenates were centrifuged at
4C, 15 000 rpm for 10 min and the soluble
fraction was retained. Protein concentrations
of s u p e r n a t a n t s were measured by the
method of Bradford (1976) using bovine
serum albumin as a standard. The degree of
lipid peroxidation was assessed by measuring
malondialdehyde (MDA) levels in plasma and
tissue samples (Yoshoiko et al., 1979). Total
super oxide dismutase (SOD) activity in the
homogenates a n d plasma samples was
determined according to the method of Sun
et al. (1988).NO concentration in plasma and
tissue samples was determined indirectly by
measuring the nitrite levels based on Griess
reaction (Cortas and Wakid, 1990).
Data were analyzed using SPSS
statistical software (SPSS 9.05 for Windows)
for one way ANOVA and post hoc multiple
comparison test.

Results and Discussion

It was observed in the present study that
induction of diabetes caused a significant
decrease in body weight (by 25%) at the end
of 2 1 day study (Table 1). Gluconeogenesis
in cells is stimulated t o compensate their
Table 1

Effects of lycopene supplementation on the change

in body weight (g) in STZ-diabetic rats
(mean 2 SE)
Day

COlltrO~
@QUP

Diabetic
group

Diabetic
group+lycopene

199213.73

19027.16

183210.43

224215.31

162+_10.45*

162k9.96'

14

242d9.22

149+-5.80*"

169d0.55**

21

24446.07

140e4.71**x

177-+10.56**+

*P<0.05,**P<O.OOl, ***P<O.OOOl, compared with the control

(none) value. 'P<0.05, compared with the STZ-diabetic group.

19

Hypoglycemic and antioxidative effects of lycopene

Table 2.

Fasting plasma glucose concentrations

in rats (mg/dl; mean 2 SE)
group

Diabetic
group

Diabetic
group+lycopene

11921.90

126k9.15

122&5.58

11521.24

455k25.93"

403+20.20*

120+1.86

384&22.00*

376k15.89"

14

11424.18

398210.03"

358+11.40*'

21

13923.62

40123.93*

296238.99**+

Day

Control

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Significantly different from the control a t *P<O.OOOl,

**P<O.OOl; significantly different from diabetes group 'Pc0.05.

glucose requirement and therefore, body

weights are decreased in diabetes (Sindhu et
al., 2004). On t h e other hand, oral
administration of 10 mg/kg/day lycopene
significantly prevented STZ-depressed body
weight in our study. This finding is consistent
with the studies of Uchiyama and Yamaguchi
(2005) and Maritim et al. (2002) which were
carried out with P-cryptoxanthin a n d
P-carotene, respectively, in STZ-diabetic rats.
Oral administration of lycopene had a
significant preventive effect (about 25%) on
the increase in plasma glucose levels of STZdiabetic rats (Table 2). The mechanism by
which lycopene administration h a s this
partial preventive effect is unknown.
Increased free radical levels impair insulin
action and glucose disposal in the peripheral
tissues (Ceriello and Motz, 2004). The
present findings demonstrate t h a t oral
supplementation by lycopene has a partial
but significant preventive effect against

diabetic hyperglycemia. Similar to our result

Uchiyama and Yamaguchi (2005) have shown
that supplementation by P-cryptoxanthin, a
carotenoid, reduced plasma glucose levels in
STZ-administrated rats.

NO levels were elevated two-fold by STZ

administration a n d lycopene supplementation reversed t h i s effect (Table 3).
Induction of NO formation may play a role
in the destruction of the p-cells during the
development of diabetes (Welsh et al., 1994).
It has been well known t h a t free radicals
react with lipids and cause peroxidative
changes t h a t result i n enhanced lipid
peroxidation (Zhang and Tan, 2000).
Administration of lycopene significantly
reduced both lipid peroxidation and NO
concentrations in plasma, but not in selected
tissue homogenates. Lycopene is commonly
located in cell membranes and it plays an
important role in preventing oxidative
damage t o the membrane lipids, thereby
influencing t h e thickness, strength and
fluidity of the membranes. One non-oxidative
activity is regulation of gap-junction
communication between cells. It was reported
that consumption of a carotenoid-deficient
diet significantly increased plasma levels of
MDA (Dixon et al., 1998). Recent studies
indicated t h a t carotenoids, especially
lycopene, inhibit LDL oxidation and lipid
peroxidation in humans (Bub et al., 2000).
No alterations of SOD activities were
detected either in plasma or in the selected
tissues among t h e groups. I t h a s been
suggested t h a t hyperglycemia is able t o

Table 3
Effect of lycopene administration on plasma malondialdehyde (MDA), nitric oxide (NO) and superoxide
dismutase (SOD)in lycopene treated STZ rats (mean 2 SE)
Day
MDA (prnol/l)
NO (pmol/l)
SOD (U/mg/protein)

Control group

Diabetic group

Diabetic group+lycopene

7.40 + 2.03

157.80 2 19.36*

101.29 2 17.14**?

40.65 2 17.30
3.97

1.51

82.82
4.53

14.11***
2

1.59

24.86 2 7.46'
6.23

3.11

Significantly different from the control at *P<O.OOOl, **P<O.OOl, ***P<0.05;significantly different from diabetics

p< 0.05.

20

V. Duzguner and coworkers

generate reactive oxygen species and that it

also either inhibits or has no effect on the
activity of antioxidant enzymes such as SOD
(Sindhu et al., 2004).

Downloaded by [125.164.98.71] at 17:34 06 January 2016

In is concluded that, supplementation of

lycopene is beneficial in preventing body
weight loss, improves lipid metabolism and
may reverse diabetic complications from lipid
peroxidation and antioxidant systems.

streptozotocin-induced diabetes in rats. Pharmacol.

Reports, 57: 90-96.
Sailaja, Y.R. Baskar, R. and Saralakumari, D. 2003. The
antioxidant s t a t u s d u r i n g m a t u r a t i o n of
reticulocytes to erythrocytes in type I1 diabetes. Free
Radic. Biol. Med., 35: 133-139.
Sindhu, R.K., Koo, R., Roberts, C.K. andvaziri, N.D. 2004.
Dysregulation of hepatic SOD, CAT and GPx in
diabetes: response to insulin and antioxidant
therapy. Clin. Exp. Hypertension, 26: 43-53.

Acknowtedgements

Steinberg, F.M. and Chait, A. 1998. Antioxidant vitamin

supplementation and lipid peroxidation in smokers.
Am. J. Clin. Nutr., 68: 319-327.

The authors acknowledge DSM Inc. (Istanbul,

Turkey) for suppIying lycopene to the study.
We thank Dr. Sandra Spence for reading the
manuscript.

Sun, Y.,Oberley, L.W. and Ying, L. 1988.A simple method

for clinical assay of superoxide dismutase. Clin.
Chem., 34: 497-500.

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