




































_____________________________________________________________________________________________________ 
 
*Corresponding author: E-mail: eeyeboah@uew.edu.gh; 
 
 
 

Asian Journal of Immunology 
 
4(1): 180-189, 2021; Article no.AJI.76491 
 

 
 

 

 

Effects of Copper and Zinc Supplementation on 
Haematological, Renal and Liver Function in Healthy 

Wistar Rats 
 

Emmanuel Effah-Yeboah a*, Emmanuel Agyapong Asare b,  
Janice Dwomoh Abraham a, Papa Kofi Amissah Reynolds a, Joshua Dwomoh a, 

Eldith Adongo a, Stephen Appiah a and Gadafi Iddrisu Balali c, d 
 

a 
Department of Biological Sciences Education, College of Agriculture Education, Akenten Appiah-
Menka University of Skills Training and Entrepreneurial Development, Mampong-Ashanti, Ghana. 

b 
Department of Chemistry Education, College of Agriculture Education, Akenten Appiah-Menka 

University of Skills Training and Entrepreneurial Development, Mampong-Ashanti, Ghana. 
c 
Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and 

Technology, Kumasi, Ghana. 
d 
Department of Science, SDA College of Education, Agona-Ashanti, Ghana. 

 
Authors’ contributions 

 
This work was carried out in collaboration among all authors. All authors read and approved the final 

manuscript. 

 
Article Information 

 
Open Peer Review History: 

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peer review comments, different versions of the manuscript, comments of the editors, etc are available here: 

https://www.sdiarticle5.com/review-history/76491 

 
 
 

Received 20 September 2021  
Accepted 27 November 2021 
Published 30 December 2021 

 
 

ABSTRACT 
 

Copper and zinc are essential elements that aid in various physiological and biochemical functions. 
Nevertheless, exposure to these heavy metals could also be detrimental to some vital organs such 
as the liver and kidney of the body. Increased usage of agrochemicals in crop production has the 
potential of increasing bioaccumulation of trace elements in both humans and animals                               
as they feed on these plants. The present study, therefore, investigated the effects of                          
copper and Zinc supplementation on haematological, renal, and liver functions in healthy   wistar 
rats. 
A total of twenty-five wistar rats of five weeks old (weighing 185g-250g) were recruited for the study. 
Animals were grouped into five namely Control, Zinc low, Zinc high, Copper low and                           
Copper high as groups 1, 2, 3, 4, and 5 respectively and administered feeds containing low and high 

Original Research Article 



 
 
 
 

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181 

 

doses of Copper and Zinc two weeks post-acclimatization. Laboratory investigations on 
haematological, renal, and liver markers were assessed after three weeks of                                   
feeding.  
Both copper and Zinc doses significantly (P <0.05) elevated the counts for Red Blood Cell (RBC), 
Hemoglobin (Hb), Hematocrit (HCT), White Blood Cells (WBCs), and Platelets with no significant 
effect on their weight gain compared to the control group of rats. Zinc doses elevated the levels of 
Alanine transaminase (ALT), with a low dosage having a significant effect on AST and ALP. The 
effect of copper and Zinc doses significantly (P <0.05) reduced creatinine levels, with no significant 
effect on urea concentrations. 
The elevation of ALT and Platelets as a result of Copper and Zinc exposure suggests their 
deteriorating effect on the liver and other organs of the body. Long-term exposure to these trace 
elements can lead to a lot of pathologies.   

 

 
Keywords: Copper; zinc; haematological; renal; liver function. 
 

1. INTRODUCTION 
 
Copper and Zinc play functional roles in diverse 
physiological and biochemical activities in the 
body [1,2]. Their effects on the improvement of 
enzymatic activities, protein synthesis, and 
stabilization of DNA and RNA have made them 
ideal for consumption [3,4,5]. Nonetheless, 
extreme exposure could be detrimental to vital 
organs of the human body [6,5].  Long-term 
exposure to these metals has been associated 
with the slow progression of physical, muscular, 
and neurological degenerative processes that 
mimic diseases like Parkinson’s disease and 
Alzheimer’s disease [7,8]. 
 
Anthropogenic activities such as mining, 
smelting, and the use of agrochemicals in 
farming have immensely contributed to the 
release of these metals into the environment 
[9,10]. Although chemical fertilizers, pesticides, 
and weedicides increase plant yield, their 
application has been associated with the 
accumulation of trace elements such as Copper 
and Zinc in the leaves, stems, and roots of crops 
[11,12]. Consumption of leafy vegetables may 
therefore expose humans to these heavy metals 
[13,14]. 
 
Available reports suggest increased human 
exposure to heavy metals, a result of rapid 
growth and applications in agriculture, industrial, 
domestic, and technology [15]. While there have 
been studies on heavy metal exposure, these 
have largely been limited to assessing their 
levels and concentrations in environmental 
matrices (soil, water, and vegetables) 
[1,16,17,18]. The few available reports however 
evaluated the concentration of heavy metals in 
the animal rearing system and the administration 

of Copper Sulphate on markers of renal functions 
and feeding patterns of Wistar rats [19,20]. 
 
Recent studies point to increasing concentrations 
of heavy metals in both medicinal plants and 
herbal distillates, leading to the production of 
reactive oxygen species upon human 
consumption and exposure [21,22,23]. Based on 
these reports, we suspect that exposure to heavy 
metals (Copper and Zinc) may result in 
pathophysiological effects in humans. Therefore, 
we qualitatively, investigated the effects of 
Copper and Zinc supplementation on 
haematological, renal, and liver function in 
healthy Wistar rats. 
 

2. MATERIALS AND METHODS 
 

2.1 Study Design 
 
Twenty-five (25) male and female Wistar rats 
(185g – 250g) aged five weeks old were 
randomly selected for the experiment. These rats 
were obtained from the Pharmacological farm of 
Kwame Nkrumah University of Science and 
Technology (KNUST), Ghana. 
 

2.2 Study Site 
 
Animal housing and treatment were carried out at 
the laboratory of the Department of Science 
Education, University of Education, Winneba, 
Asante Mampong Campus. Hematological, 
Renal, and Liver tests were done at EDEP 
Laboratory service, Santasi –Kumasi, Ghana. 
 

2.3 Maintenance of Animals 
 
Rats were housed in a one-tier hutch during the 
study. They were kept in animal rooms at the 



 
 
 
 

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182 

 

laboratory where room temperature was 

maintained at 26±3∘C under a 12-hour light-dark 
cycle.  
 
The rats were thoroughly examined and any 
abnormalities and/or ailments were recorded 
before the research began. Two hundred and 
twenty-five grams (225 g) of concentrate feed 
was weighed with a Camry dial spring scale 
(ISO9001 APPROVED) every morning and given 
to the animals as their daily feed. Feeding and 
water troughs were cleaned every morning 
before feeding.  
 

2.4 Preparation of Feed 
 
After two weeks of acclimatization, experimental 
rats were purely subjected to concentrate feed. 
The feed was formulated and prepared at the 
University of Education, Winneba, Mampong 
campus (UEW-M) laboratory. Ingredients were 
made up of, wheat brand (5 kg/30 kg); maize (15 
kg/30 kg); concentrate (10 kg/30 kg); Copper 
Sulphate and Zinc tablet. They were weighed 
according to their required quantities with the 
Camry dial spring scale (ISO9001 APPROVED). 
The measured quantities were thoroughly mixed 
by spade, bagged, and then stored in the 
animals’ feed room. 
 

2.5 Preparations and Treatments  
 
A total of 25 experimental rats were used to 
assess the effect of Copper and Zinc on the 
haematological, renal, and liver markers. Animals 
were divided into five (5) groups and housed 
under controlled environmental conditions. 
Copper sulphate (CuSO4) and Zinc tablet used 
for the study were obtained from UEW-M 
laboratory and Laugh Pharmacy (Mampong-
Ashanti) respectively.  
 
In the preparation of the wheat brand maize 
concentrate with CuSO4 treatment, an amount of 
3.929 g and 0.982 g of CuSO4 powder was 
weighed for the high and low concentrations 
respectively using an electronic scale. It was 
then dissolved in 200ml distilled water and was 
uniformly mixed with 5 kg of the feed 
concentrate. Also, for the zinc treatment, 200 g 
and 50 g of zinc tablets were dissolved in 200 ml 
distilled water for the high and low doses 
respectively. It was uniformly mixed with 5 kg of 
the feed concentrate. The mixture was bagged 
and stored in the animals’ feed room. Each group 
was given an equal amount of feed throughout 
the experimental period. Weekly measurements 

of weight were recorded.  The Five treatments 
used for the study were; 
 

Group 1 (control) fed on wheat brown maize 
concentrate and water. 
Group 2 (Zinc low) fed on wheat brand maize 
concentrate with low zinc ppm  
Group 3 (Zinc High) fed on wheat brand maize 
concentrate with high zinc ppm  
Group 4 (Copper High) fed on wheat brand 
maize concentrate with high CuSO4 ppm  
Group 5 (Copper low) fed on wheat brand maize 
concentrate with low CuSO4 ppm.  
 

2.6 Haematological and Biochemical 
Parameters 

 

Experimental rats were sacrificed and blood was 
dispensed into EDTA tubes and then analyzed 
for haematological markers such as red blood 
cells (RBCs), haemoglobin (Hb), hematocrit 
(HCT), mean corpuscular volume (MCV), mean 
corpuscular haemoglobin (MCH), mean 
corpuscular haemoglobin concentration (MCHC) 
using an automated haematology analyzer 
(MSLAB 12, China). Another portion of blood 
was collected in empty vacutainer tubes and 
centrifuged at 13000 rpm for 5 mins. The serum 
was then retrieved and biochemical parameters 
such as AST, ALT, ALP, TB, TP, creatinine, and 
urea concentrations in serum were analyzed 
using commercially available kits and a standard 
BS-120 Mindray Chemistry Analyzer. 
 

2.7 Statistical Analysis 
 

GraphPad Prism Version 5.0 for Windows 
(GraphPad Software, San Diego, CA, USA) was 
used for data analysis. Data were presented as 
mean ± SEM online graphs and tables. For 
comparing the control and treatment groups, 

independent samples  -tests for the significance 
of differences were used. To compare the 
biological effects of the treatment, an analysis of 
variance (ANOVA) was used. Newman Keuls 
Posthoc analysis was also used to identify the 

source of the variation.   values of less than 0.05 
were considered statistically significant. 
 

3. RESULTS 
 

3.1 Effect of Copper and Zinc Doses on 
the Weight of Wistar Rats 

 

Treated groups showed a steady weight gain 
after two weeks of acclimatization, although it 
was not statistically significant (P <0.05) from the 
control group (Fig. 1). 



 
 
 
 

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183 

 

 
 

Fig. 1. Effect of Cu High, Cu Low, Zn High, and Zn Low on weight as compared with the weight 
of the CTL group 

 

3.2 Effect of Copper and Zinc Doses on 
Haematological Parameters 

 

The effects of copper and zinc dosages on 
haematological parameters were investigated 
and compared with similar parameters of normal 
control rats. Following the feed administration 
with variously defined dosages, haematological 
parameters were significantly increased            
(P <0.05) compared to the control group. 
 

3.3 Effect of Copper and Zinc Doses on 
Liver Enzymes 

 

Zinc low doses significantly (P <0.05) elevated 
the levels of the liver enzymes (AST, ALT, and 
ALP) whereas Zinc high doses only showed a 

significant (P <0.001), increase in ALT compared 
to the control. Comparing the different doses of 
copper, though not significant, the elevation of 
the biochemical markers was higher in Cu low 
than in Cu high as compared to the control group 
(Table 2). 
 

3.4 Effect of Copper and Zinc Doses on 
Renal Function 

 
Doses of all treatment groups showed a 
significant (P <0.05) reduction of creatinine levels 
compared to the control. Zinc high doses showed 
an increase in urea levels, however, urea levels 
in copper doses (low and high) and zinc low 
doses were statistically not significant (Fig. 2).  

 

 
 

Fig. 2. Effect of CuH, CuL, ZnH, and ZnL on creatinine and urea levels; Each column 
represents the Mean±SEM. (n= 5). •p <0.05, •p <0.001 compared to control group (One way 

ANOVA Followed by Newman-Keuls test) 

Weights of Rats

initial Week 1 Week 2 Week 3
0

100

200

300

400
CTL

CuH

CuL

ZnH

ZnL

creatinine levels

C
TL

C
uH

C
uL

Z
nH Z

nL

0

50

100

150

 
 

Urea Levels

C
TL

C
uH C

uL
Zn

H
Zn

L

0

2

4

6

8

10



 
 
 
 

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184 

 

Table 1. Effect of Cu High, Cu Low, Zn High, and Zn Low on levels of haematological markers as compared with the control 
 

 RBC  (10
6
/µL)      Hb (g/DL)   HCT (%) MCV(fL) MCH(pq) MCHC(g/dL) MPV(fL) PLATELETS (10

3
/ µL) WBC (103/dL) 

CTL 5.6± 0.1 10.6±0.1 35.00±1.0 59.1±0.7 19.32±0.3 31.78±0.3 9.06±0.4 26.18±2.9 2.36±0.2 
CuH 8.3±0.2••• 13.98±0.3••• 51.46±1.3••• 62.96±1.2 17.12±0.3•• 27.2±0.5••• 9.8±0.2 897.6±111.3••• 8.82±0.2••• 
CuL 8.1±0.2••• 14.04±0.3••• 50.52±1.5••• 62.4±1.6 17.34±0.3•• 27.9±0.2••• 9.42±0.3 779.2±67.2••• 5.69±0.7•• 
ZnH 9.0± 0.5••• 15.22±0.6••• 56.3±2.2••• 60.78±0.8 16.88±0.4••• 27.64±0.4••• 9.20±0.2 805.3±53.6••• 13.25±1.1••• 
ZnL 7.4±0.2••• 13.06±0.2••• 44.82±1.6••• 60.64±1.1 17.70±0.4•• 29.2±0.9•• 8.70±0.3 767.8±45.9••• 11.71±0.6••• 

Each column represents the Mean±SEM. (n= 5). •p <0.05, ••p <0.001, •••p <0.0001 compared to control group (One way ANOVA Followed by Newman-Keuls 
test) 

 
Table 2. Effect of Cu High, Cu Low, Zn High, Zn Low on levels of enzymes and proteins associated with the liver (ALT, AST, ALP, GLB, ALB, TP) 

 

 ALT (U/l)           AST (U/l)           ALP (U/l)           GLOBULIN (g/l)                   ALBUMIN(g/l)        TOTAL PROTEIN (g/l)        

CTL 100.5± 1.99 172.4±25.7 235.9±20.3 50.2±1.8 28.4±1.7 5.5±0.1 
CuH 79.6±4.56 195.0±21.7 339.5±72.9 56.24±1.3 28.8±1.4 5.8±0.3 
CuL 102.6±7.6 235.8±9.4 388.5±52.4 48.74±1.2 29.2±0.4 6.2±0.2 
ZnH 157.6±26.9•• 227.1±12.6 299.1±55.8 57.94±6.6 28.12±0.6 4.4±0.6 
ZnL 147.3±12.3• 259.8±25.1• 783.2±201• 63.8±6.2 27.36±1.8 5.6±0.7 

Each column represents the Mean±SEM. (n= 5). •p <0.05, ••p <0.001 compared to control group (One way ANOVA Followed by Newman-Keuls test) 



 
 
 
 

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4. DISCUSSION 
 
The present study investigated the effects of 
Copper and Zinc supplementation on 
haematological, renal, and liver markers in 
healthy Wistar rats. The effects of these trace 
elements administered as feeds significantly (P 
<0.05) elevated the haematological markers of 
the treated rats compared to the control. This 
agrees with [24] who reported significant (P 
<0.05) changes in haematological parameters, 
especially white blood cells (WBC) following the 
administration of copper oxide and/or zinc oxide 
nano-particles on rats. Also, a study by [25] 
showed a significant (P <0.05) increase in red 
blood cells (RBCs), haemoglobin (Hb), and 
hematocrit (HCT) following zinc supplements.  
 
The significant elevation of the haematological 
parameters such as RBC, Hb, WBC, and 
platelets counts, as shown in Table 1 following 
the supplementation of these trace elements may 
be a result of bone marrow deficiency leading to 
left shift production of these markers [26]. Also, 
high platelets count suggests reactive 
thrombocythemia as a result of bone marrow 
suppression. This is in line with studies that 
suggest that persistent hyperglycemia 
predisposes individuals to thrombogenesis with 
platelet aggregation as a result of acute zinc 
supplements thereby prolonging bleeding time 
[27,28]. 
 
The high elevation of RBC and Hb following 
Copper sulphate exposure suggest vascular 
oxidative stress which can lead to impaired 
oxygen delivery hence the increment in its count 
for homeostatic balance [24]. This is supported 
by findings from Lucas and Rifkinds [29] who 
reported a pronounced increase in RBC and Hb 
as a result of vascular oxidative stress following 
copper bound amyloid-β peptide (CuAβ) 
exposure.  
 
The observed significant difference between 
treatment and control groups in some of the 
enzymes associated with liver function (ALT) 
following zinc doses (high and low) 
administration suggests organ damage, 
especially in the liver. Low levels of ALT are 
generally considered a good marker of liver 
health; however, low levels of ALT occur as a 
result of certain underlying medical conditions 
such as deficiency in Vitamin B6 or chronic 
kidney disease. Also, high levels of ALT are a 
good indicator of damage caused to liver cells 
such as liver inflammation and cirrhosis [30].  

 
Serum alanine transaminases (ALT) are not only 
measured to determine possible liver damage 
but also useful in monitoring the general health 
status [31, 32, 33]. This is an enzyme that is 
mainly found in the cytosol of the hepatocytes 
and plays a role in gluconeogenesis [34]. ALT is 
released as a result of liver injury from the injured 
liver cells into the serum, which causes the levels 
to increase significantly in the serum [35, 36]. 
Also, only low doses of zinc treatment 
significantly (p <0.05) affected most of the liver 
enzymes (ALT, AST, ALP) indicating the 
essential role of zinc and hence it's right 
proportional supply to the body). Zinc deficiency 
may induce oxidative stress, compromise the 
function of oxidative-sensitive transcription 
factors that can affect cell function, proliferation 
and survival. Again, it can also result in cell and 
tissue damage by modulating specific signal 
cascades with resulting damage to enzymes, 
mitochondria and ribosomal structures. Hepatic 
damage following Zinc deficiency sides with 
other studies that report on zinc deficiency as a 
predisposing factor for acute and chronic liver 
disease [37, 38]. 
 
Copper doses, both high and low did not have 
any significant effect on the enzymes associated 
with liver function. This can be correlated to the 
significant reduction of creatinine levels following 
copper treatment. The observable insignificant 
effect of copper doses on renal function may be 
due to the body’s homeostatic mechanism of 
regulating excess copper via bile secretion by the 
liver [39, 40].  
 
Urea is a principal Nitrogenous waste product of 
metabolism as a result of protein deamination 
[41], its physiological role in the detoxification of 
ammonia and conservation of water in the kidney 
has made it ideal as a biomarker for renal 
function [42]. Even though statistically, no 
significant differences were observed in the 
treatment groups compared to control regarding 
blood urea levels, its slight increment following 
high doses of zinc treatment cannot be 
overlooked. The insignificant differences 
observed may be because blood urea levels are 
only affected following an extreme reduction of 
the Glomerular filtration rate [43]. 
 
Albumin and direct bilirubin levels were found to 
be very low as compared to their normal ranges. 
Bilirubin acts as an antioxidant that protects 
tissues throughout the body from damage by 
substances that can cause the breakdown of 



 
 
 
 

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cells. Given this, lower levels of bilirubin indicate 
a possibility of certain body parts being 
vulnerable to damage. Several medical 
conditions are associated with lower levels of 
bilirubin in the body. These conditions include 
ulcerative colitis, brain lesions and diabetic 
retinopathy [44, 33, 24, 45, 25]. On the other 
hand, lower levels of albumin are associated with 
inflammation, shock and the inability of the body 
to absorb and digest protein. 
 

5. CONCLUSION  
 
Results from the study reviewed that, Copper 
and Zinc at both high and low doses caused high 
elevation of haematological markers. This affirms 
the essential role of Cu and Zn in blood formation 
and immunity in the body. However, low levels of 
Zn yielded low liver and renal markers, this 
suggest that long-term exposure to Zinc can 
have a deteriorating physiological and 
pathological effects on the liver and other organs 
of the body.  
 

6. RECOMMENDATIONS 
 
Based on the findings of this current study, it is 
recommended that;  
 

 Further studies should be carried out to 
ascertain the histopathological effects of 
copper and zinc on the liver and          
kidney.  

 Whenever Cu and Zn treatments are 
administered orally to rats, there may be a 
high propensity of the gut of the rats being 
affected, it is therefore recommended that 
further investigation be made to study the 
effects of Cu and Zn on the gut of rats as 
well as possible microbiota present in the 
gut. 

 The Food and Agriculture Organization 
(FAO) and the Ministry of Food and 
Agriculture (MOFA) must ensure strict 
compliance to permissible levels of trace 
elements in pesticides used in crop 
production. 

 Farmers must be educated on the dangers 
of breaching the permissible levels of trace 
elements on-farm produce as                     
well as in the supplementation of animal 
diets. 

 

DISCLAIMER 
 
The products used for this research are 
commonly and predominantly use products in our 

area of research and country. There is absolutely 
no conflict of interest between the authors and 
producers of the products because we do not 
intend to use these products as an avenue for 
any litigation but for the advancement of 
knowledge. Also, the research was not funded by 
the producing company rather it was funded by 
personal efforts of the authors. 
 

ETHICAL APPROVAL 
 
All animal experiments, procedures, and 
techniques used in this study were conducted in 
compliance with the National Institute of Health 
Guidelines for Care and Use of Laboratory 
Animals, with ethical approval from the 
Institutional Review Board, University of Cape 
Coast, Ghana (ethical clearance number: UCC 
IRB/CHAS/2017). 
 

COMPETING INTERESTS 
 
Authors have declared that no competing 
interests exist. 
 

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Accessed on: 24
th
 May 2020 

Available: www.nature/scientific report.com 
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© 2021 Effah-Yeboah et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution 
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