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*Corresponding author: E-mail: pkorisadiran@pgschool.lautech.edu.ng; 
 
 
 

Asian Journal of Immunology 
 
3(1): 11-22, 2020; Article no.AJI.53370 
 

 
 
 

 

Effects of D-Ribose-L-Cysteine on Lipid Profile, 
Atherogenic Index and Infertility in Streptozotocin-

Induced Male Diabetic Wistar Rats 
 

Abiodun Oluwabusola Adedeji1,2 and Patrick Kunle Orisadiran3* 
 

1
Department of Anatomy, Olabisi Onabanjo University, Ago Iwoye, Nigeria.  

2Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. 
3Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. 

 
Authors’ contributions  

 
This work was carried out in collaboration between both authors. Author AOA participated in study 

design, data collection and interpretation, contributed to drafting/ revising of manuscript. Author PKO 
participated in study design, data analysis and interpretation, did literature search and drafted/edited/ 

revised manuscript. Both authors read and approved the final manuscript. 
 

Article Information 
 

Editor(s): 
(1) Dr. Jaffu Othniel Chilongola, Department of Biochemistry and Molecular Biology, Kilimanjaro Christian Medical University 

College, Tumaini University, Tanzania. 
Reviewers: 

(1) Rupali Sengupta, India. 
(2) Ann Nkeiruka, National Root Crops Research Institute, Nigeria. 

Complete Peer review History: http://www.sdiarticle4.com/review-history/53370 

 
 
 
 

Received 02 November 2019  
Accepted 07 January 2020 

Published 20 January 2020 

 
 

ABSTRACT 
 

Aims: The present study aimed at determining the effects of D-Ribose-L-Cysteine on lipid profile, 
atherogenic index, and infertility in streptozotocin-induced diabetic male Wistar rats.  
Methods: A total of twenty-eight adult male Wistar rats were divided into four groups of seven rats 
each. 1: Normal control group, 2: Diabetic control group, 3: Normal rats treated with 30 mg/kg body 
weight of D-Ribose-L-cysteine, 4: Diabetic rats treated with 30 mg/kg body weight of D-Ribose-L-
cysteine. Group 2 and 4 were injected intraperitoneally with a single dose of streptozotocin (STZ) 
(65 mg/kg in 0.1 M cold citrate buffer, pH 7.5) prior to D-Ribose-L-cysteine treatment. Group 4 were 
subsequently administered D-Ribose-L-cysteine orally 72 hours post administration of 
streptozotocin, twice daily for 28 days. Parameters tested include: fasting blood and serum 
glucose, malondialdehyde (MDA) concentration, sperm motility, morphology and count. 
Testosterone (TT), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were also 
examined.  

Original Research Article 



 
 
 
 

Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 
 
 

 
12 

 

Results: The results showed that diabetic rats showed weights loss, increased MDA, increase 
blood and serum glucose levels, elevated lipid profile, altered TT, FSH and LH as well as reduced 
sperm count, motility and morphology. These effects were ameliorated in diabetic rats treated with 
D-Ribose-L-cysteine.  
Conclusion: Current study revealed that D-Ribose-L-Cysteine attenuates the oxidative stress in 
streptozotocin-induced diabetic rats on blood glucose, lipid profile, reproductive hormone and 
sperm parameters. 
 

 
Keywords: D-Ribose and L-Cysteine; wistar rats; diabetic rat; sperm; hormone; streptozotocin. 
 
1. INTRODUCTION 
 
Diabetes mellitus is a group of metabolic 
disorders resulting from a deficiency in insulin 
secretions and/or actions [1]. This deficiency, in 
turn, leads to accumulation of glucose in the 
bloodstream with obstruction of carbohydrate, fat 
and protein metabolism. Disease progression 
results in tissue damage leading to severe 
diabetic complications such as impairment or 
loss of vision, impairment of kidney function, 
cardiovascular and microbial complications [2]. 
The world prevalence of diabetes among adults 
between 20 and 79 years was estimated to be 
6.4%, affecting 285 million adults, in 2010, and 
will increase to 7.7% and 439 million adults by 
2030 [3]. Out of the two types of diabetes (insulin 
dependent and non-insulin dependent), the 
incidence of non-insulin dependent diabetes 
mellitus is much higher than the insulin-
dependent diabetes mellitus [4].  
 
Glucose is the main oxidizable substrate in 
various cell types. Homeostasis is maintained in 
a diabetic state by the activation of catabolic 
pathways such as gluconeogenesis and 
glycogenolysis [5]. As a result, lipolysis is also 
increased, which trigger dyslipidemia, a risk 
factor for the development of atherosclerosis that 
affects 97 percent of diabetic patients [6,7]. 
 
Dyslipidemia is characterized by elevated levels 
of triacylglycerol plasma and total cholesterol, 
increasing the concentration of very low-density 
lipoproteins (VLDL-cholesterol) and low-density 
lipoproteins (LDL-cholesterol) and decreasing the 
concentration of high-density lipoproteins (HDL-
cholesterol) [7,8]. 
 

In different studies by Valko et al. [9] and 
Schilling [10], they showed that an increase in 
LDL-cholesterol that occurs due to the release of 
oxidizing agents during the metabolic pathways 
activated by hyperglycemia is directly related to 
the development of atherosclerosis, the 
inflammatory process triggered by the oxidation 

of LDL-cholesterol. Oxidized LDLs are 
phagocytosed by macrophages in the 
subendothelial layer, thereby transforming into 
foam cells that contribute to the formation of 
atherosclerotic plaque and, consequently, 
atherosclerosis [6,11]. 
 
Reproductive disorders in diabetic males have 
been widely studied. Experimental studies by 
O’Neill et al. [12] and Ricci et al. [13] revealed 
different structural and physiological reproductive 
dysfunctions in cases of diabetes in males. 
Diabetes mellitus affects male reproductive 
functions at multiple levels as well as its negative 
effects on endocrine control of spermatogenesis 
and/or by impairing erection and ejaculation [14]. 
Ricci et al. [13] established that insulin-
dependent diabetes is accompanied by reduced 
semen volume and decreased sperm motility and 
vitality. This corroborates with the report of 
Agbaje et al. [15] which stated that a high level of 
blood sugar in the bloodstream may affect sperm 
quality and consequently decreases male fertility 
potentials. Also, Joao and co. [16] confirmed high 
rates of infertility and poor reproductive 
outcomes in diabetic men compared with healthy 
men. 
 
Therefore, effective control of the blood glucose 
level is crucial in preventing, controlling or 
reversing diabetic complications associated with 
diabetics, thus improving the quality of life in 
diabetic patients [17]. A study has shown that 
antioxidant substances can reduce chronic 
degenerative diseases such as diabetes mellitus 
and its complications [18]. Antioxidants are 
stable substances that act as reducing agents 
capable of reducing oxidized substances and 
making them stable, thus repairing the structure 
of the cellular macromolecules [19].  
 
D-ribose is an antioxidant and a prodrug form of 
L-cysteine known to aid the elevation of 
intracellular levels of glutathione (GSH) [20]. 
GSH is a coenzyme that mediates the protection 
against free radicals generated during the 



 
 
 
 

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13 

 

oxidative metabolism of acetaminophen by the 
hepatic cytochrome P-450 system [21]. Whole 
glutathione consumption cannot be effective 
because it would be destroyed in the digestion 
process before reaching the cell. The ribose 
component of the D-Ribose-L-Cysteine solves 
these challenges allowing the cells to produce 
glutathione when needed by effectively 
protecting and delivering the fragile cysteine 
molecule [22]. 
 

In view of the discussed above, this study aimed 
to determine the beneficial effects of D-Ribose-L-
Cysteine on lipid profile, atherogenic index, and 
infertility in streptozotocin-induced diabetic male 
Wistar rats. 
  

2. MATERIALS AND METHODS 
 
2.1 Chemicals  
 
Streptozotocin (STZ) was a product of Sigma 
Chemical Company St. Louis U.S.A. All assay 
kits were from Randox Laboratories Limited UK. 
Chemicals and reagents used were of analytical 
grade. D-Ribose-L-Cysteine supplement was 
obtained from Max International, Salt Lake City, 
Utah, USA.  
 

2.2 Experimental Design 
 
A total of 28 Albino rats of Wistar strain, with an 
average weight of 160 g were obtained from the 
Animal House of Physiology Department, Ladoke 
Akintola University of Technology, Nigeria. The 
animals were divided into 4 groups of 7 rats each 
and housed in separate cages in the same 
environment. The animals were allowed to 
acclimatize in the laboratory for two weeks 
before the commencement of the experiments. 
 

2.3 Diabetes Induction 
 
Streptozotocin (65 mg/kg in 0.1 M cold citrate 
buffer, pH 7.5) was administered to Wistar rats 
fasted overnight by interperitoneally injection of 
freshly prepared solution. The animals were 
considered as diabetic if the blood glucose 
values of the overnight fasted rats, were > 250 
mg/dl on the third day.  
 

Group 1: Control rats given citrate buffer only 
(0.01 M, pH 7.5),  

 

Group 2: Diabetic control (untreated rats) 
 

Group 3: Rats treated with 30 mg/kg body weight 
of D-Ribose-L-cysteine. 

Group 4: Diabetic rats treated with 30 mg/kg 
body weight of D-Ribose-L-cysteine  

 
The diabetic rats were then kept for 24 hours on 
5% glucose solution bottles in their cages to 
prevent hypoglycemia. Blood was collected every 
3 days through the rat’s tail vein for glucose 
estimation using One Touch Glucometer; After 
28 days of treatment, the body weight and 
fasting blood glucose, serum glucose of the 
animals were again determined.  
 

2.4 Collection of Blood  
 
The rats were fasted overnight after 28 day, 
anaesthetized with chloroform and sacrificed. 
Blood was collected by cardiac puncture into 
plain sample bottles, allowed to coagulate                    
and then centrifuged at 3000 rpm for 15 minutes 
to obtain serum. The serum was kept                      
under refrigeration at 4ºC for biochemical 
examination.  
 

2.5 Biochemical Examination 
 
Serum total cholesterol was determined using 
the method of Zak [23], plasma triglyceride 
estimated by the method of Mendez et al. [24], 
HDL-C by Lopez- Vitrella et al.  [25], LDL-C and 
VLDL triglyceride values were calculated by the 
modified method of Friedewald formula [26]. 
Serum MDA was measured by a thiobarbituric 
acid assay procedure [27].  
 

2.6 Semen Analysis 
 
The caudal epididymis of the rats was incised 
and a drop of epididymal fluid was smeared onto 
a glass slide, covered by a 22 · 22 mm. The slide 
was examined under the light microscope at 100 
magnification to evaluate different fields [28]. 
After assessing different microscopic fields, the 
relative percentage of motile sperm was 
estimated and reported to the nearest 5% using 
the subjective determination of motility [29]. The 
sperm count was determined using the Neubauer 
improved hemocytometer. The epididymal fluid 
ratio of 1:20 was prepared by adding 0.1 ml of 
fluid to 1.9 ml of water. The dilution was mixed 
thoroughly and both sides of the counting 
chamber were scored and the average was 
taken. Spermatozoa within five of the red blood 
cell squares including those which lie across the 
outermost lines at the top and right sides were 
counted, while those at the bottom and left sides 
were left out. The number of spermatozoa 
counted was expressed in millions/ml [30]. 



 
 
 
 

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2.7 Reproductive Hormones 
 
The serum levels of testosterone, luteinizing 
hormone (LH) and Follicle-stimulating hormone 
(FSH) were measured using enzyme-linked 
immunoassay kit (Abcam) according to the 
manufacturer’s instructions. 

 
2.8 Statistical Analysis  
 
Results were presented as Mean ± SD. Paired 
Student’s t-test was used to compare variations 
amongst groups. The minimum level of 
significance was considered at p˂0.05. Statistical 
analysis was carried out using a software 
program (GraphPad Prism Ver. 5; GraphPad 
Software, San Diego, CA). 

 
3. RESULTS  
 
3.1 Effect of D-Ribose-L-Cysteine on 

Bodyweight and Serum Glucose on 
STZ Induced Diabetic Rats 

 
There was a significant increased (p<0.05) in the 
bodyweight of normal control and D-Ribose-L-
Cysteine treated group whereas the body weight 
of diabetic rats significantly reduced during the 
period of the experiment (Fig. 1). The blood 
glucose levels increased significantly (p < 0.05) 
after the induction of diabetes but after the 
administration of D-Ribose-L-Cysteine the     
blood glucose levels also decreased significantly 
(p < 0.05) compared to the diabetic control     
(Fig. 2a).  

 
The serum glucose level in the diabetic                
control group (15.5±1.3 mmol/L) was significantly 
(P<0.05) higher compared to normal control 
group (6.4±1.3 mmol/L), while treated               
diabetic rats showed a slight significant 
decreased (P<0.05) in the serum glucose 
(9.7±1.2 mmol/L) compared to the diabetic 
control rats (Fig. 2b). 

 
3.2 Effect of D-Ribose-L-Cysteine on 

Lipid Peroxidation in STZ Induced 
Diabetic Rats 

 
Figure 3 shows the changes in serum MDA 
concentration. The mean value of serum MDA 
levels in the diabetic rats (7.77±0.78 nmol/ml) 
significantly increased (p<0.05) when compared 
with the normal control (5.7±0.90 nmol/ml) but 
significantly decreased (p<0.05) in diabetic rats 

treated with D-Ribose-L-Cysteine (5.93±0.89 
nmol/ml).  
 

3.3 Effect of D-Ribose-L-Cysteine on 
Lipid Profile in STZ Induced Diabetic 
Rats 

 

Serum levels of normal and diabetic rats treated 
with D-Ribose-L-Cysteine are shown in Figure 4. 
Diabetic control rats exhibited higher serum Total 
cholesterol, LDL-cholesterol, triglycerides, and 
low HDL-cholesterol levels compared to those of 
normal rats. The total cholesterol, LDL-
cholesterol and triglycerides levels were 
significantly higher (p<0.05) in diabetic control 
rats compared to the D-Ribose-L-Cysteine 
treated rats (97.50±10.50, 45.23±12.34 and 8 
5.49±13.80 mg/dL), D-Ribose-L-Cysteine treated 
diabetic rats (105.20±7.30, 33.67±12.54 and 
92.62±14.30 mg/dL), and normal control rats 
(110.50±7.80, 43.98±15.23 and 89.407.80, 
mg/dL) respectively. Whereas LDL-cholesterol 
levels of rats treated with D-Ribose-L-Cysteine 
are not significantly different when compared 
with the normal control rats.  
 

3.4 Effect of D-Ribose-L-Cysteine on 
Sperm Parameters in STZ Induced 
Diabetic Rats 

 

The mean percentage of sperm motility after 28 
days of treatment is shown in Figure 5. Sperm 
motility in the diabetic control group (35.3±7.5%) 
was significantly lower (p<0.05) when compared 
to the normal control group (87.7±9.1%). 
Treatment of diabetic group with D-Ribose-L-
Cysteine produced a more pronounced effect 
with an increased in sperm motility (69.5 ±9.6%). 
The movement of sperm in D-Ribose-L-Cysteine 
treated group were similar to the normal control 
group (Fig. 5). 
 

As shown in Figure 5, Streptozotocin-induced 
diabetic control group showed a significant 
decreased (p<0.05) in sperm morphology 
(37.6±6.3%) as compared with the normal control 
group (84.2±6.9). There was significantly 
increased (p<0.05) in mean sperm morphology in 
D-Ribose-L-Cysteine treated group and D-
Ribose-L-Cysteine treated diabetic group (85.90 
± 7.00 and 70.0±10.1) in comparison with the 
diabetic control group (Fig. 5). 
 

There was a significant decreased in sperm 
count value in the diabetic control group (33.5± 
7.50, p<0.05) when compared with normal 
control group ((86.8± 7.70), D-Ribose-L-Cysteine 
treated rats (93.7±7.00) and D-Ribose-L-



 
 
 
 

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15 

 

Cysteine treated diabetic rats (75.5± 7.11.8)   
(Fig. 5). 

 
3.5 Effect of D-Ribose-L-Cysteine on 

Reproductive Hormones in STZ 
Induced Diabetic Rats 

 
Testosterone levels decreased significantly (p < 
0.05) in diabetic group compared to non-diabetic 
normal control. There was no significant 
difference in testosterone levels of animals that 
received D-Ribose-L-Cysteine compared with 
normal control, but it increased significantly       
(p < 0.05) compared to diabetic control group 
(Fig. 6). 
 

There was no significant difference in FSH of 
normal control and D-Ribose-L-Cysteine groups; 
however, there was a significant increase of FSH 
in animals that received D-Ribose-L-Cysteine 
group and D-Ribose-L-Cysteine diabetic group 
compared to diabetic group (Fig. 6). 
 

Luteinizing hormone levels increased 
significantly (p < 0.05) in the D-Ribose-L-
Cysteine group compared to diabetic control 
groups. However, diabetic animals administered 
D-Ribose-L-Cysteine had significantly decreased 
(p < 0.05) levels of LH compared to normal 
control. FSH decreased significantly (p < 0.05) in 
the diabetic control group and compared with 
non-diabetic normal control (Fig. 6).  

NC DC DRC DRCD
0

50

100

150

200

250
Initial

Final

*

*

**

Parameters
Figure 1: Effect of D-Ribose-L-Cysteine on Body weight in STZ induced diabetic rats.

Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05).
** Significantly different from normal and diabetic controls (p<0.05).

NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD:
D-Ribose-L-Cysteine treated diabetic rats

W
ei

gh
t 

(g
)

 

NC DC DRC DRCD
0

100

200

300

400

500
Initial

Final
*

**

Figure 2a: Effect of D-Ribose-L-Cysteine on blood glucose in STZ induced diabetic rats.

Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05).

 ** Significantly different from normal and diabetic controls (p<0.05).   Significantly different from Initial Fasting Blood glucose (p<0.05)

 NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats

F
as

ti
ng

 b
lo

o
d 

g
lu

co
se

  (
m

gd
l-1

)

 
 



 
 
 
 

Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 
 
 

 
16 

 

NC DC DRC DRCD
0

5

10

15

20

**

**

*

Figure  2b: Effect of D-Ribose-L-Cyste ine  on serum glucose  in STZ induced diabetic rats.

Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05).
** Significantly different from normal and diabetic controls (p<0.05).

NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD:
D-Ribose-L-Cysteine treated diabetic rats

S
er

um
 c

on
ce

nt
ra

ti
on

  
(m

m
ol

L
-1

)

 

0

2

4

6

8

10
NC

DC

DRC

DRCD

*

**

**

MDA
Figure 3: Effect of D-Ribose-L-Cysteine on lipid peroxidation in STZ induced diabetic rats.

Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05).
 ** Significantly different from normal and diabetic controls (p<0.05). NC: Normal Control,

DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats , DRCD: D-Ribose-L-Cysteine treated diabetic rats

C
on

ce
nt

ra
ti

on
  (

nm
ol

m
l-1

)

 

TC HDL-C LDL-C TG
0

50

100

150
NC

DC

DRC

DRCD

*

** *

* **

**

*

*

*

* *

Figure 4: Effect of D-Ribose-L-Cysteine on lipid profile in STZ induced diabetic rats.
Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05).

** Significantly different from normal and diabetic controls (p<0.05). NC: Normal Control,
DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats.
TC: Total Cholesterol, HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol

TG: Triglycerides

C
o
n
ce

nt
ra

ti
on

  (
m

gd
L

-1
)

 



 
 
 
 

Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 
 
 

 
17 

 

 

TT (ngdl-1) FSH (miuL-1) LH (miuL-1)
0

2

4

6

8

10
NC

DC

DRC

DRCD

*
*

*

**
**

** **

**

Figure 6: Effect of D-Ribose-L-Cysteine on reproductive hormone in STZ induced diabetic rats.

Values are expressed as Mean ± SD, * signif icantly different from normal control group (p<0.05).

 ** Signif icantly dif ferent from normal and diabetic controls (p<0.05). NC: Normal Control,

DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats.

TT: Testosterone, FSH:  Follicle stimulating hormone, LH:  Lutenizing hormone

C
o

n
c
e
n

tr
a
ti

o
n

 
4. DISCUSSION  
 

Diabetes mellitus is a chronic metabolic disease 
with debilitating complications. Two types are 
mostly described in the literature; type 1(insulin-
dependent diabetes mellitus) and type-2 (insulin-
resistant diabetes mellitus) [1]. These two 
interestingly, though have distinct pathogenesis, 
share similar life-threatening complications such 
as long-term hyperglycemia, which is associated 
with many other complications, including male 
reproductive dysfunctions and infertility [29]. 
Over 90% of diabetic patients are known to suffer 
from severe insulin resistance, which leads to 
severe metabolic and reproductive complications 
[30,31]. 
 
Hwang et al. [32] and Chen et al. [33] in a 
different study reported the toxic effects of STZ 

on pancreatic beta cells. These effects lead to a 
decrease in insulin production as well as less 
cellular absorption of glucose resulting in glucose 
toxicity, increased ROS and beta cells apoptosis. 
Hence, the usage of chemical substances that 
will aid the cellular sensitivity to insulin 
consequently ameliorate and prevent glucose 
toxicity [34]. The present study aims to 
investigate the ameliorative effect of D-Ribose-L-
Cysteine on the blood glucose, lipid peroxidation, 
lipid profile and reproductive system in adult 
male Wistar rats. 
 

Kalaiarasi and Pugalendi [35] reported a severe 
loss in body weight in streptozotocin-induced 
diabetes. The decrease in the bodyweight of 
diabetic rats in this study was due to the 
cytotoxic effects of streptozotocin on cells 
leading to loss or degradation of structural 

Motility (%) Morphology (%) Sperm count (x106/ml)
0

50

100

150
NC

DC

DRC

DRCD

*

**

*

**

*

**

Figure 5:Effect of D-Ribose-L-Cysteine on Sperm parameters in STZ induced diabetic rats.

Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05).

 ** Significantly different from normal and diabetic controls (p<0.05). NC: Normal Control,

DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats



 
 
 
 

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18 

 

proteins to provide amino acids for 
gluconeogenesis during insulin deficiency 
resulting to muscle wasting and weight loss. The 
protein content is decreased in muscular tissue 
by proteolysis due to insulin deficiency [36]. In 
the present study, diabetic control rats showed a 
marked reduction in their body weights when 
compared to normal control rats. The weight loss 
was reversed by the administration of D-Ribose-
L-Cysteine to the diabetic rats.  In addition, 
glucose reacts with proteins in a non-enzymatic 
manner leading to the development of Amadori 
products followed by the formation of advanced 
glycation end-products AGEs; ROS is generated 
at multiple steps during this process [37]. 
Elevated lipid peroxidation in tissues will result in 
a concomitant decrease in body weights [38] as 
seen in this study. D-Ribose-L-Cysteine 
administered maintained the body weights of the 
animals protecting them from the cytotoxic 
effects of streptozotocin. These results suggest a 
possibility of D-Ribose-L-Cysteine to either 
improve pancreatic beta cells function or prevent 
lipid peroxidation by impairing the formation of 
ROS or increasing the production of antioxidants 
to neutralize ROS generated.  Increased 
oxidative stress and changes in the antioxidant 
capacity as observed in this study have been 
implicated in the etiology of chronic diabetes 
complications as reported by Van et al. [39] and 
Omotayo et al. [38].  
 
This study demonstrated that streptozotocin 
increased lipid peroxidation. The elevated levels 
of oxidative stress markers have been 
associated with hyperglycemia which is due to 
the shortfall in insulin as a result of beta cell 
dysfunction [40,41]. This anomaly has been 
associated with complications including 
cardiovascular diseases in diabetes mellitus as 
reported by Omotayo et al. [38] and George et al. 
[42]. These negative effects of streptozotocin 
were ameliorated by D-Ribose-L-Cysteine. Since 
streptozotocin is known to destroy pancreatic 
beta cells leading to a concomitant increase in 
glucose availability- hyperglycemia [43], 
therefore, the possible mechanism of action of D-
Ribose-L-Cysteine is mediated through 
influencing glucose uptake or utilization by 
tissues and probably regeneration of beta cells. 
Hyperglycemia may result in glucose toxicity and 
increase in ROS activity as well as increased 
lipid peroxidation especially in the pancreas with 
low antioxidants level [44]. This is in tandem with 
the increased serum MDA levels of the diabetic 
controls rats in this study. Furthermore, the 
decreased MDA levels as seen in animals that 

received D-Ribose-L-Cysteine showed an 
abrogation of cellular redox.  
 
In this study, there was an increased in total 
cholesterol, LDL-cholesterol, triacylglycerides, 
and low HDL-cholesterol in diabetic rats, 
confirming the development of dyslipidemia 
which is supported by previous studies [45,46]. 
Insulin deficiency in diabetes mellitus results in 
increased lipolysis and subsequent �-oxidation of 
acetyl-CoA, a key enzyme in cholesterol 
biosynthesis used in lipogenesis together with 
HMG-CoA reductase [46], thereby promoting the 
hepatic formation of VLDL-cholesterol and 
consequently increasing serum levels of 
cholesterol and LDL-cholesterol. Fatty acids that 
are not �-oxidated are esterified into 
triacylglycerols which are incorporated into 
VLDL-cholesterol in the liver and exported to the 
bloodstream [47]. These metabolic events 
increased lipoproteins to a value above normal in 
the present study, identifying dyslipidemia as a 
risk factor for the development of atherosclerosis 
[46].  Improved dyslipidemia in diabetic rats 
treated with D-Ribose-L-Cysteine can be 
explained by the greater insulin secretion in the 
presence of this antioxidant, D-Ribose-L-
Cysteine, since insulin decreases blood sugar 
levels and lipolysis in adipose tissue. Studies 
have shown that D-Ribose-L-Cysteine increases 
insulin secretion. On the other hand, Ayyasamy 
and Leelavinothan [46] revealed that insulin 
increases the activity of lipoprotein lipase, which 
catalyzes the breakdown of triacylglycerol ester 
bonds thereby increasing the clearance of VLDL-
cholesterol. 
 
Also, the increased insulin level as seen in 
diabetic control rats elevates the activity of 
lecithin cholesterol acyltransferase and the 
enzyme responsible for extracellular cholesterol 
esterification, thus increasing the efficiency of 
reverse cholesterol transport, indicating an 
inverse correlation with cardiovascular accidents 
[48,46]. Studies have identified a relationship 
between antioxidants and reduced cholesterol 
levels, due to inhibition of HMG-CoA reductase 
activity and cholesterol biosynthesis [49,46]. 
Thus, the D-Ribose-L-Cysteine administered in 
diabetic rats was able to normalize the 
atherogenic index because it was possible to 
control the lipid profile, a finding that is 
corroborated by Yang et al. [50], who reported 
that an increased atherogenic index is related to 
low antioxidant activity. Thus, D-Ribose-L-
Cysteine was able to reduce the formation of 
atherosclerotic plaque by lowering blood glucose 



 
 
 
 

Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 
 
 

 
19 

 

levels, the glycation of LDL-cholesterol, and its 
consequent oxidation in the present study. 
 
The increased antioxidant levels by D-Ribose-L-
Cysteine in diabetic rats enhanced the 
production of FSH and LH by the anterior 
pituitary gland [51] which promotes follicle 
development and testosterone synthesis. 
Administration of D-Ribose-L-Cysteine in the 
study was found to improve the percentage 
sperm motility and sperm count. The antioxidant 
activity of this substance may be attributed to the 
reduction or amelioration of oxidative-stress 
induced diabetic complications such as lipid 
peroxidation, by elevation of antioxidant enzyme 
activities as observed from this study. In addition, 
previous studies involving treatments with 
antioxidant compounds demonstrate their 
importance in regulating β- pancreatic cell 
functions and growth, thereby reducing the 
complications due to diabetes [52,53]. 
 
The antioxidant activities of D-Ribose-L-Cysteine 
may also be responsible for the restoration of β-
cells’ integrity and metabolic functions, while at 
the same time ensuring maximum synthesis of 
insulin by these cells necessary for glucose 
tolerance [52]. Therefore, helps to reverse the 
reproductive dysfunctions associated with 
diabetes as seen in the present study [54,55]. 
This study further strengthens previous findings 
by Ballester et al.  [56] and Suthagar et al.  [57] 
that intraperitoneal administration of high doses 
of alloxan in male rats induces type-1 
diabetogenic conditions, which leads to 
reproductive complications such as reduced 
testicular and epididymal weights, decreased 
testosterone production, reduced sperm motility 
and sperm counts, and also decrease in the 
gonadal function of both leydig (testosterone 
producing) cells and sertoli (supporting) cells.  

 
5. CONCLUSION 
 
In conclusion, D-Ribose-L-Cysteine therefore, 
revealed in the current study to attenuate the 
oxidative stress in streptozotocin-induced 
diabetic rats on blood glucose, lipid profile, 
spermatogenesis, and steroidogenesis. D-
Ribose-L-Cysteine could be used as adjuvant 
therapy for the reduction of atherosclerosis and 
infertility in diabetic subject because of its potent 
antioxidant property. 
 

CONSENT 
 
It is not applicable. 

ETHICAL APPROVAL 
 
The protocol of the study was approved by the 
Local Ethical Committee for animal 
experimentation of the Faculty of Basic Medical 
Sciences of Olabisi Onabanjo University, Nigeria. 
 

ACKNOWLEDGEMENT  
 
The authors especially thank Mr. Akinrinola and 
Sharphor Enterprises for their support during the 
course of this study.  
 

COMPETING INTERESTS 
 
Authors have declared that no competing 
interests exist. 
 

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