Food and Nutrition Sciences, 2013, 4, 82-89
http://dx.doi.org/10.4236/fns.2013.47A010 Published Online July 2013 (http://www.scirp.org/journal/fns)
Biological Effect of Sucralose in Diabetic Rats
Helen N. Saada1, Nefissa H. Mekky2, Hassan A. Eldawy1, Abeer F. Abdelaal2
1Radiation Biology Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt;
2Zoology Department, Faculty of Sciences, Ain Shams University, Cairo, Egypt.
Received March 12th, 2013; revised April 15th, 2013; accepted April 23rd, 2013
Copyright © 2013 Helen N. Saada et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Among people that might take a large amount of sucralose, are diabetic people who are attempting to modify their car-
bohydrate intake. The objective of this study is to evaluate the impact of sucralose; an artificial sweetener derived from
sucrose, at a dose approximately twice the ADI on hyperglycemia, hyperlipidemia and oxidative stress in diabetic rats.
Diabetes was induced in male albino rats after an intraperitoneal streptozotocin injection (65 mg/kg body weight). Ani-
mals with fasting blood glucose levels ≥250 mg/dl were considered diabetics. Sucralose was dissolved in water and
administered to rats daily by oral gavages during a period of 6 weeks at a dose of 11 mg/kg body weight. Animals were
divided into 4 groups and treated in parallel for 6 weeks. Control: rats received distilled water, Sucralose: rats received
sucralose, Diabetic: diabetic rats received distilled water, Diabeticrats + Sucralose: diabetic rats received sucralose. The
administration of sucralose to diabetic rats provoked a significant decrease (P < 0.05) of serum glucose and triglyceride
levels, a significant increase (P < 0.05) of total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high den-
sity lipoprotein-cholesterol (HDL-C), while has no effect (P > 0.05) on insulin, compared to their respective values in
diabetic rats receiving distilled water. Biochemical analysis in brain and testis tissues showed that sucralose has no ef-
fect (P > 0.05) on superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glucose-6-phosphate
dehydrogenase (G-6-PDH) activities, and glutathione content (GSH), while reduced thiobarbituric acid reactive sub-
stances level (TBARS) (P < 0.05), compared to their respective values in diabetic rats receiving distilled water. It could
be concluded that consumption of sucralose didn’t induce oxidative stress, has no effect on insulin, reduce glucose ab-
sorption and intensify hypercholesterolemia in STZ-induced diabetic rats. Accordingly it is advised that diabetic people
consuming high amount of sucralose must check their lipid profile to avoid diabetic complications.
Keywords: Sucralose; Diabetes; Antioxidants; Brain; Testis; Glucose; Lipids
1. Introduction
Diabetes mellitus, or simply diabetes, is a metabolic dis-
ease characterized by chronic hyperglycemia. There are two
main types of Diabetes: Type I also called insulin-depen-
dent diabetes (IDDM), is a severe, chronic form of dia-
betes caused by insufficient production of insulin and Type
II also called non-insulin dependent diabetes (NIDDM)
result from insulin resistance, a condition in which cells
fail to use insulin properly and generally associated with
pancreatic beta-cell dysfunction. Oxidative stress defined
as an imbalance between oxidants and antioxidants plays
an important role in the development of diabetic compli-
cations [1]. There are various mechanisms suggested to
contribute to the formation of reactive oxygen species in
diabetes.
Glucose oxidation is believed to be the main source of
free radicals. In its enediol form, glucose is oxidized in a
transition-metal dependent reaction to an enediol radical
anion that is converted into reactive ketoaldehydes and to
superoxide anion radicals that undergo dismutation to
hydrogen peroxide. Hydrogen peroxide (H2O2) in the pre-
sence of transition metals, can lead to production of ex-
tremely reactive hydroxyl radicals. Superoxide anion ra-
dicals can also react with nitric oxide to form reactive
peroxynitrite radicals [2]. Hyperglycemia is also found to
promote lipid peroxidation of low density lipoprotein
(LDL) by a superoxide-dependent pathway resulting in
the generation of free radicals [3]. Brownlee [4] demon-
strated that hyperglycemia-induced generation of super-
oxide anion radicals at the mitochondrial level is the initial
trigger of vicious cycle of oxidative stress in diabetes.
Another important source of free radicals in diabetes is the
interaction of glucose with proteins leading to the forma-

Biological Effect of Sucralose in Diabetic Rats 83
tion of advanced glycation endproducts (AGEs), which
activate the transcription factor NF-κB and enhances
production of nitric oxide, which is believed to be a me-
diator of islet beta cell damage [5].
Efficient defense and repair mechanisms exist in living
cells to protect against oxidant species. Superoxide dis-
mutase (SOD) catalyzes the dismutation of superoxide
anion to hydrogen peroxide (H2O2). Catalase serves to
detoxify H2O2 by catalyzing a reaction between two
H2O2 molecules, resulting in the formation of H2O and
O2. In addition, catalase can promote the interaction of
H2O2 with compounds that can serve as hydrogen donors
so that the H2O2 can be converted to one molecule of
H2O, and the reduced donor becomes oxidized (a process
sometimes called the peroxidatic activity of catalase) [6].
Glutathione Peroxidase/Glutathione Reductase system
which includes the enzymes glutathione peroxidase (GSH-
Px) and glutathione reductase and the co-factors reduced
glutathione (GSH) and NADPH. Together, these mole-
cules effectively remove H2O2 with formation of oxi-
dized glutathione, which is recycled back to GSH by
GSH-reductase, using the cofactor NADPH generated by
glucose 6-phosphate dehydrogenase [7].
According to the International Diabetes Federation,
percent of diabetes was 11.4% in the year 2010 and this
likely to increase to 13.7% by the year 2030. This alarm-
ingly increasing incidence of diabetes encouraged the
growth of the artificial sweetener industry. Sucralose, one
of the newest artificial sweeteners has been approved by
the Food and Drug Administration in 1998 and made avail-
able to the consumer under the trade name SPLENDA®.
Sucralose is obtained from sucrose where three hydro-
xylic groups, from positions 4, 1 and 6 are replaced by 3
chlorine atoms to form the compound 4,1’ and 6’tri-
chlorogalacto-sacarose also known as 1,6-dichloro-1,6-
dideoxy-β-D fructo-furanosyl-4-chloro-4-deoxy-α-D ga-
lacto-pyranoside [8]. In the European Union, it is also
known under the E number E955. Sucralose is approxi-
mately 600 times as sweet as sucrose twice as sweet as
saccharin, and 3.3 times as sweet as aspartame. The com-
mercial success of sucralose-based products stems from
its favorable comparison to other low-calorie sweeteners
in terms of taste, stability, and safety [9]. According to
Binns [10] it is stable in the presence of ethanol and able
to be stored for more than one year while maintaining
99% of its original flavor. Its characteristics are pre-
served, even during pasteurization, sterilization and cook-
ing at high temperatures. According to food and drug ad-
ministration (FDA) the acceptable daily intake (ADI) for
sucralose is 5 mg per kilogram of body weight per day
[11].
Studies performed on the metabolism of sucralose
showed that when administered orally to mice at doses of
1000, 1500 and 3000 mg/kg body weight/day, urinary
elimination averaged, respectively 23%, 15% and 16%,
indicating that even with augmented administration of
sucralose, there is no corresponding rise in absorption
[12,13]. Studies indicate the existence of 2 hydrolysis
products of sucralose, 4-chloro-4-deoxy-Dgalactose (4-
CG) and 1,6-dichloro-1-6-dideoxy-D-fructose (1,6-DCG)
that are more rapidly absorbed after oral administration
than the original sucralose compound. The hydrolysis
product 4-CG is excreted, essentially in intact form, in
the urine, while 1,6-DCF follows one of two principal
metabolic pathways: reduction to 1,6 dichloroaminnitol,
rapidly excreted in unaltered form in the urine, or conju-
gated with glutathione [14].
Studies investigating the safety of sucralose consump-
tion revealed conflicting results [15]. It has no adverse
effects on the central nervous system [16], immune sys-
tem, reproductive performance [17,18], and red blood
cells constituents and morphology [19]. Conversely, some
reports suggest sucralose is a possible trigger for some
migraine patients [20]. A Duke University study, found
evidence that sucralose limit the bioavailability of orally
administered drugs [21]. However, an expert panel, re-
ported the Duke study to be deficient in several critical
areas that preclude reliable interpretation of the results
[22]. Motwani et al. [23] reported that the reduced form
of vitamin B12 reacts readily with sucralosein an aqueous
system to form an alkylcobalamin. Given the human con-
sumption of sucralose from food and beverages, such a
reaction could occur in vivo.
Among consumers that might take a large amount of
sucralose, are diabetic people who are attempting to
modify their carbohydrate intake. The objective of this
study is to evaluate the impact of sucralose at a dose ap-
proximately twice the ADI on oxidative stress in the brain
and testis of STZ-induced diabetic rats, besides its effect
on serum glucose and insulin levels and lipid profile.
2. Materials and Methods
Male Sprague-Dawley rats (10 ± 2 weeks old; 100 - 120
g) were purchased from the Egyptian Organization for
Biological Products and Vaccines (Cairo, Egypt) and
used for the different investigations carried out in the
present study. Animals in specially designed cages, were
maintained in conditions of good ventilation, normal
temperatures and humidity ranges, and kept under ob-
servation for one week prior to experimentation. The rats
received standard pellets, containing all nutritive ele-
ments (proteins, fats, carbohydrates, vitamins, salts and
minerals). Drinking water and food were provided ad
libitum throughout the study.
All animal procedures were performed in accordance
with the Ethics Committee of the National Research
Centre conformed to the “Guide for the care and use of

Biological Effect of Sucralose in Diabetic Rats 84
Laboratory Animals” published by the National Institutes
of Health (NIH publication No. 85-23, revised 1996).
2.1. Induction of Diabetes
Streptozotocin (STZ) was purchased from Sigma chemi-
cal company, St. Louis Missouri, USA, in the form of 1 g
vials. Diabetes was induced by administering intraperi-
toneal injection of a freshly prepared solution of STZ (65
mg/kg BW) in 0.1 M cold citrate buffer (pH 4.5) to the
overnight fasted rats [1]. Since STZ is capable of pro-
ducing fatal hypoglycemia as a result of massive pancre-
atic release of insulin, the rats were kept on 5% glucose
for the next 24 hrs to prevent hypoglycemia. Blood glu-
cose levels were monitored using an Accu-check blood
glucose meter (Roche Diagnostics, Basel, Switzerland) in
tail vein 72 h after STZ administration. Rats with blood
glucose levels ≥250 mg/dl were considered diabetics.
2.2. Sucralose Treatment
Sucralosewas obtained as SPLENDA® (McNeil Nutri-
tionals, LLC, and Fort Washington, PA, USA) in the
form of 1 g packets (yellow color). According to North-
land Laboratories (Northbrook, IL), Splenda contents are
sucralose (1.10%), glucose (1.08%), moisture (4.23%),
and maltodextrin (93.59%). The content of each packet
was dissolved in distilled water and administered to ani-
mals by oral gavages in a way that each animal received
1 ml distilled water containing 11 mg sucralose/Kg body
weight/day which is approximately twice the FDA ac-
cepted daily intake.
2.3. Animal Groups
Experimental animals were randomly divided into 4
groups of 10 rats each as follows: Control group: Normal
healthy rats received distilled water during 6 weeks via
gavages. Sucralose: Rats received sucralose during 6
weeks via gavages. Diabetic: diabetic rats received dis-
tilled water daily during 6 weeks via gavages, Diabetic +
Sucralose: Diabetic rats received sucralose daily during 6
weeks via gavages.
2.4. Biochemical Analysis
The animals were sacrificed after a fasting period of 12
hours. Rats were anaesthetized with light ether and blood
samples obtained via heart puncture by sterilized syringe.
The blood was left to coagulate to obtain the serum after
centrifugation at 1000 g for 15 minutes (K3 Centurion
Scientific Ltd, London, UK).
Glucose content was determined following the method
described by Trinder [24] using a T60 UV/VIS spectro-
photometer, PG instruments, London, UK. Insulin con-
centration was determined using Radio-Immuno Assay
device from “Axiom Veterinary Laboratories Ltd.”, Ger-
many. Serum lipid profile was assessed by the determi-
nation of triglycerides, total cholesterol, high density
lipoprotein-cholesterol (HDL-C) and low density lipo-
protein-cholesterol (LDL-C) levels. Triglycerideslevel
was determined following the method described by Fos-
sati and Prencipe [25]. Total cholesterol was determined
following the method described by Richmond [26]. For
the determination of HDL-C: the chylomicron fractions,
LDL-C, and VLDL-C are precipitated quantitatively by
phosphotungestic acid in the presence of magnesium ions.
After centrifugation, the cholesterol concentration in the
HDL fraction which remains in the supernatant was de-
termined. LDL-C content was determined according to
the Friedewald’s [27] equation LDL-C = TC − (HDL-C
− TG/5).
For the evaluation of antioxidant biomarkers a portion
of brain and testis tissue was weighed and 10% weight/
volume tissue homogenate prepared in 0.1 M phosphate
buffer (pH 7.4) using Teflon homogenizer (Glass-Col,
Terre Haute, Ind., USA). The commercial kit from bio-
diagnostic Egyptian Company was used for the determi-
nation of superoxide dismutase (SOD) [28], catalase [29],
glutathione peroxidase (GSH-Px) [30], and glucose-6-
phosphate dehydrogenase activities (G-6-PDH) [31], and
glutathione (GSH) content [32] using a T60 UV/VIS
spectrophotometer, PG instruments, London, UK.
2.5. Statistical Analysis
All values are presented as mean ± S.E.M. All groups
were compared by one-way analyses of variance (ANOVA)
and post hoc multiple comparisons were done with Dun-
can test in SPSS/PC software program (version 12.0;
SPSS Inc., Chicago, IL, USA) to determine the differ-
ences in all parameters. Differences were considered
statistically significant at P ≤ 0.05.
3. Results
The administration of sucralose to normal healthy rats
provoked a significant decrease of −14% of glucose level
(P < 0.05) while has no effect on insulin level (P > 0.05).
An increase of 20% for total cholesterol content (P <
0.05), 25% for HDL-C content (P < 0.05), 38% for LDL-
C content (P < 0.01), and a decrease of −17% for triglyc-
erides content (P < 0.05) were recorded, regarding their
respective values in the control group of rats receiving
distilled water (Table 1).
In the diabetic group of rats glucose content showed
an increase of 222% (P < 0.001), while insulin content
showed a decrease of −25% (P < 0.05), compared to their
respective control values. Furthermore, the results showed
an increase of 26% for total cholesterol content (P <
0.05), a decrease of −25% for HDL-C content (P < 0.05),

Biological Effect of Sucralose in Diabetic Rats 85
an increase of 75% for LDL-C content (P < 0.001), and
98% for triglycerides content (P < 0.001), regarding their
respective values in the control group (Table 1).
In the diabetic + sucralose group of rats glucose con-
tent showed an increase of 150% (P < 0.001), while insu-
lin content showed a decrease of −22% (P < 0.05), com-
pared to their corresponding values in the control group
receiving distilled water. The results showed an increase
of 46% for total cholesterol content (P < 0.01), a de-
crease of −14% for HDL-C content (P < 0.05), an in-
crease of 138% for LDL-C content (P < 0.001), and an
increase of 56% for triglycerides content (P < 0.01), re-
garding their corresponding values in the control group.
Accordingly, it appears that the administration of su-
cralose to diabetic rats induced a decrease of glucose
content (P < 0.001), while has no effect on insulin con-
tent (P > 0.05). Moreover, the administration of sucralose
to diabetic rats induced an increase of total cholesterol
content (P < 0.05), HDL-C content (P < 0.05), LDL-C
content (P < 0.01), and induced a decrease of triglyc-
erides content (P < 0.05), compared to their respective
levels in the diabetic rats receiving distilled water (Table
1).
From the data in Tables 2 and 3 it is observed that the
administration of sucralose to normal healthy rats has no
effect on TBARS content, SOD, catalase, GSH-Px, and
G-6-PDH activities and GSH content (P > 0.05) in the
brain and testis, compared to their respective values in
the control group receiving distilled water.
In the diabetic group of rats TBARS content showed
an increase of 29% (P < 0.05) in the brain and 22% (P <
0.05) in the testis, SOD activity an increase of 71% (P <
0.01) in the brain and 22% (P < 0.05) in the testis, cata-
lase activity showed no significant change (P > 0.05) in
the brain and testis, GSH-Px activity showed an increase
of 106% (P < 0.001) in the brain and 122% (P < 0.001)
in the testis, G-6-PDH activity, an increase of 127% (P <
0.001) in the brain and 92% (P < 0.01) in the testis and
GSH content an increase of 24% (P < 0.05) in the brain
and 17% (P < 0.05) in the testis, compared to their re-
spective values in the control group (Tables 2 and 3).
In the diabetic + sucralose group of rats TBARS con-
tent showed an increase of 17% (P < 0.05) in the brain
and 12% (P < 0.05) in the testis, SOD activity an in-
crease of 65% (P < 0.01) in the brain and 18% (P < 0.05)
in the testis, catalase activity showed no significant
change (P > 0.05) in the brain and testis, GSH-Px activ-
ity, showed an increase of 100% (P < 0.001) in the brain
and 142% (P < 0.001) in the testis, G-6-PDH activity, an
increase of 123% (P < 0.001) in the brain and 94% (P <
0.01) in the testis, and GSH content an increase of 29%
(P < 0.05) in the brain and 19% (P < 0.05) in the testis,
compared to their respective values in the control group.
Accordingly it appears that the administration of su-
Table 1. Effect of sucralose on some serum metabolites.
Animal
groups
Parameters
ControlSucralose Diabetic Diabetic +
Sucralose
Glucose (mg/dl) 100 ± 486 ± 7
P < 0.05a
322±25
P < 0.001a
250 ± 30
P < 0.001a
P < 0.001b
Insulin (µIU/ml)27 ± 1.129 ± 2.4
P > 0.05a
20±1.1
P < 0.05a
21 ± 0.8
P < 0.05a
P > 0.05b
Total cholesterol
(mg/dl) 69 ± 5.583 ± 3.3
P < 0.05a
87 ± 7.0
P < 0.05a
101 ± 6.0
P < 0.01a
P < 0.05b
HDL-C (mg/dl) 40 ± 3.250 ± 2.0
P < 0.05a
30 ± 2.7
P < 0.05a
34 ± 2.6
P < 0.05a
P < 0.05b
LDL-C (mg/dl) 16 ± 1.322 ± 0.9
P < 0.01a
28 ± 2.3
P < 0.001a
38 ± 2.3
P < 0.001a
P < 0.01b
Triglycerides
(mg/dl) 63 ± 5.052 ± 2.1 P < 0.05a
125 ± 9.9
P < 0.001a
98 ± 6.0
P < 0.01a
P < 0.05b
Each value represents the mean ± standard error (n = 10); Means were com-
pared by one-way analyses of variance (ANOVA) and post hoc multiple
comparisons were done with Duncan test in SPSS/PC software program
(version 12.0; SPSS Inc., Chicago, IL, USA) to determine the differences in
all parameters; aSignificance vs control group; bSignificance vs diabetic
group.
Table 2. Effect of sucralose on oxidant and antioxidant bio-
markers in ra t brain.
Animal
groups
Parameters
ControlSucralose Diabetic Diabetic +
Sucralose
TBARS
(nmol/g tissue) 1430 ± 571426 ± 71 P > 0.05a
1845 ± 102
P < 0.05a
1673 ± 107
P < 0.05a
P < 0.05b
SOD
(U/g tissue) 172 ± 7160 ± 6 P > 0.05a
293 ± 17
P < 0.01a
284 ± 12
P < 0.01a
P > 0.05
Catalase
(U/g tissue) 83 ± 9 85 ± 10
P > 0.05a
87 ± 7
P > 0.05a
89 ± 10
P > 0.05a
P > 0.05b
GSH-Px
(mU/g tissue) 78 ± 5 79 ± 4 P > 0.05a
161 ± 14
P < 0.001a
156 ± 15
P < 0.001a
P > 0.05b
G-6-PDH
(U/g tissue) 2.35 ± 0.122.47 ± 0.24 P > 0.05a
5.33 ± 0.13
P < 0.001a
5.24 ± 0.30
P < 0.001a
P > 0.05b
GSH
(mg/g tissue) 1.72 ± 0.091.75 ± 0.07
P > 0.05a
2.13 ± 0.16
P < 0.05a
2.21 ± 0.16
P < 0.05a
P > 0.05b
Each value represents the mean ± standard error (n = 10); Means were com-
pared by one-way analyses of variance (ANOVA) and post hoc multiple
comparisons were done with Duncan test in SPSS/PC software program
(version 12.0; SPSS Inc., Chicago, IL, USA) to determine the differences in
all parameters; aSignificance vs control group; bSignificance vs diabetic
group.
cralose to diabetic rats induced a significant decrease (P
< 0.05) of TBARS content in brain and testis. While has
no effect (P > 0.05) on SOD, catalase, GSH-Px, and G-

Biological Effect of Sucralose in Diabetic Rats 86
Table 3. Effect of sucralose on oxidant and antioxidant bio-
markers in rat testis.
Animal
groups
Parameters
Control Sucralose Diabetic Diabetic +
Sucralose
TBARS (nmol/g
tissue) 696 ± 44 706 ± 5 P > 0.05a
846 ± 100
P < 0.05a
779 ± 105
P < 0.05a
P < 0.05b
SOD (U/g tissue) 286 ± 11 262 ± 11
P > 0.05a
349 ± 20
P < 0.05a
337 ± 16
P < 0.05a
P > 0.05b
Catalase
(U/g tissue) 181 ± 10 186 ± 11 P > 0.05a
188 ± 12
P > 0.05a
194 ± 7
P > 0.05a
P > 0.05b
GSH-Px
(mU/g tissue) 88 ± 6 84 ± 5 P > 0.05a
195 ± 16
P < 0.001a
234 ± 20
P < 0.001a
P > 0.05b
G-6-PDH
(U/g tissue) 2.67 ± 0.20 2.72 ± 0.40 P > 0.05a
5.00 ± 0.20
P < 0.01a
5.17 ± 0.50
P < 0.01a
P > 0.05b
GSH (mg/g tissue) 2.39 ± 0.12 2.25 ± 0.09
P > 0.05a
2.79 ± 0.21
P < 0.05a
2.85 ± 0.22
P < 0.05a
P > 0.05b
Each value represents the mean ± standard error (n = 10); Means were com-
pared by one-way analyses of variance (ANOVA) and post hoc multiple
comparisons were done with Duncan test in SPSS/PC software program
(version 12.0; SPSS Inc., Chicago, IL, USA) to determine the differences in
all parameters; aSignificance vs control group; bSignificance vs diabetic
group.
6PDH activities and GSH content, compared to their re-
spective levels in the diabetic rats receiving distilled wa-
ter (Tables 2 and 3).
4. Discussion
The impact of artificial sweeteners on human health is
still a matter of controversial debate. Sucralose, a chlo-
rinated sugar 600 times as sweet as sugar is widely used
in beverages, frozen desserts, chewing gum, baked goods,
and other foods. Safety concerns pertaining to sucralose
revolve around the fact that it belongs to a class of
chemicals called organochlorides, some types of which
are toxic or carcinogenic; however, the presence of chlo-
rine in an organic compound does not in any way ensure
toxicity. In the current study, the administration of su-
cralose at a dose approximately twice the FDA accepted
daily intake to diabetic rats provoked a significant de-
crease (P < 0.05) of serum glucose and triglyceride levels,
a significant increase (P < 0.05) of total cholesterol, low
density lipoprotein-cholesterol (LDL-C), and high den-
sity lipoprotein-cholesterol (HDL-C), while has no effect
(P > 0.05) on insulin, compared to their respective values
in diabetic rats receiving distilled water. Biochemical
analysis in brain and testis tissues showed that sucralose
has no effect (P > 0.05) on superoxide dismutase (SOD),
catalase, glutathione peroxidase (GSH-Px), and glucose-
6-phosphate dehydrogenase (G-6-PDH) activities, and
glutathione content (GSH), while reduced thiobarbituric
acid reactive substances level (TBARS) (P < 0.05), com-
pared to their respective values in diabetic rats receiving
distilled water.
Diabetes mellitus is characterized by chronic hyper-
glycemia resulting from defects in insulin secretion, in-
sulin action, or both. In the current study, diabetic rats
showed a significant increase of glucose associated to a
significant decrease of insulin, level, compared to their
respective values in the control group. This could be ex-
plained by the fact that STZ induces degeneration in
Langerhans islet beta cells [33-35]. The administration of
sucralose to diabetic rats has no effect on insulin while
reduces glucose level, compared to diabetic rats receiv-
ing distilled water. The results corroborate the findings
that sucralose did not induce a cephalic insulin response
[36]. Accordingly, it appears that the decrease of glucose
might be attributed to a decrease in its absorption. Sup-
porting our postulation Abou-Donia et al. [21] reported
that the administration of sucralose at 1.1 - 11 mg/kg to
male rats for 12-week’s interfere with the absorption of
nutrients and drugs. However, contrarily to our results, in
vitro study revealed that sucralose induces insulin secre-
tion by Ca2+ and cAMP-dependent mechanisms [37] and
has no effect on the rate of glucose absorption [38].
Moreover, studies on diabetic patients (Type 1 and type 2)
showed that the administration of 1000 mg sucralose had
no effect on plasma glucose [39], as well as, the admini-
stration of 7.5 mg/kg/day sucralose during 3-months’ had
no effect on glycated hemoglobin, and fasting plasma
glucose in individuals with type 2 diabetes [40].
It is well documented that hyperlipidemia is a meta-
bolic complication of diabetes [41,42]. In the current
study, diabetic rats showed a significant increase of tri-
glycerides, total cholesterol, and LDL-C levels associ-
ated to a significant decrease of HDL-C level, when
compared to their respective values in the control group.
The increase of cholesterol might result from increased
intestinal absorption and synthesis [43] while the in-
crease of triglycerides might be attributed to the inactiva-
tion of lipoprotein lipase resulting from insulin defi-
ciency [44]. The administration of sucralose reduces the
level of triglycerides while elevates the level of total
cholesterol, LDL-C and HDL-C, when compared to their
respective levels in rats receiving distilled water. The
decrease of triglycerides might be attributed to the effect
of sucralose on the peroxisome proliferator-activated re-
ceptors-alpha (PPAR-α) thus increasing the expression of
lipoprotein lipase. In addition, activation of PPAR-γ in
adipose tissue stimulates triglyceride storage [45]. The
increase of HDL-C might result from the effect of su-
cralose on PPAR-α and activation of apo A-I and apo
A-II [46]. However, contrarily, to the results obtained,
previous studies demonstrated that administration of su-
cralose and its hydrolysis products, did not reveal sig-

Biological Effect of Sucralose in Diabetic Rats 87
nificant alterations in the content of cholesterol [47].
Experimental evidence has considered the brain vul-
nerable to oxidative stress because of its high O2 utiliza-
tion rate, its high content of polyunsaturated fatty acids,
which are prone to lipid peroxidation, its high content of
iron, which through the Fenton reactions increase the
formation of free radicals [48]. The testis also has been
reported as vulnerable to oxidative stress due to the
abundance of highly unsaturated fatty acids (particularly
20:4 and 22:6) and the presence of potential reactive
oxygen species (ROS)-generating systems [49]. The ef-
fect of diabetes on the antioxidant status is erratic, with
no discernible pattern. For example, SOD activity has
been reported to be decreased [50] or elevated [51] in the
testis. Catalase activity is consistently found to be ele-
vated in brain [52] of diabetic rats while decreased in the
testis [51]. Glutathione concentration was found to be
decreased [53] however, there is also some contradictory
evidence of increased glutathione concentration in dia-
betic rat [54]. GSH-Px activity has been seen to be either
elevated [55] or decreased [56] in the testis of STZ-in-
duced diabetic rats.
Biochemical analysis in brain and testis tissues of dia-
betic rats revealed significant increase of TBARS levels
with concomitant increase of SOD, GSH-Px and G-6-
PDH activities and GSH content, compared to their re-
spective values in the control group. The increase in the
activity of antioxidant enzymes might be a self response
of the tissues towards the increase of free radicals gener-
ated by hyperglycemia. Supporting this postulation Wei-
Chan et al. [57] recorded an increase of SOD gene ex-
pression in the brain of STZ-diabetic rats. Moreover, the
results realize the concept that induction of oxidative
stress induces mRNA species for SOD, and GSH-Px ac-
tivities [58]. The administration of sucralose has no ef-
fect on the activity of antioxidants while slightly reduces
the amount of TBARS. This unexpected effect might be
attributed to one of its hydrolysis products, 1,6-dichl-
oro-1-6-dideoxy-D-fructose (1,6-DCG) which undergoes
reduction to 1,6 dichloroaminnitol before excretion [59].
According to the results obtained in the current study it
could be concluded that excessive consumption of su-
cralose has no effect on oxidative stress and serum insu-
lin level while interfere with glucose absorption and in-
tensify hypercholesterolemia. Accordingly it is highly
recommended that diabetic people consuming large amount
of sucralose must follow their lipid profile to avoid dia-
betic complications.
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