TITLE PAGE

EVALUATION OF SHORT-TERM NEPHRO-TOXIC EFFECTS OF

ARTEMETHER LUMEFANTRINE AND CHLOROQUINE IN ALBINO RATS

A RESEARCH PROJECT PRESENTED TO THE DEPARTMENT OF BIOLOGY, FEDERAL

COLLEGE OF EDUCATION, EHA-AMUFU, ENUGU STATE

BY
NAMES REG. NUMBERS
OMEJE FAITH O. 19302122
UGWUANYI JOY C. 19302144
AGBO AGATHA E. 19302055
UGWUOKE VICTORIA O. 19302274

IN PARTIAL FULFILLMENT OF THE REQUIREMENT FOR AWARD OF NIGERIA

CERTIFICATE IN EDUCATION (N. C. E.)

MATCH, 2023
 APPROVAL PAGE
This project has been read, corrected and approved for meeting the requirement of the

Department of Biology, School of Sciences, Federal College of Education, Eha-Amufu.

………………………………… ………………………………...
Dr. E. I. Nnamonu Date
(Project Supervisor)

…………………………………. ……………………………….
Mrs. C. I. Okenyi Date
(Head of Department)

……………….………………………………..
External Examiner

Date: …………………………
 DEDICATION

This project work is dedicated to Almighty God for His intervention throughout this N.C.E.

Programme and this research.

ACKNOWLEDGEMENT
Words may not be enough to express our profound gratitude to our LORD Jesus Christ for His

mercies and sufficient grace.

Thanks to our parents, who sponsored this study and our siblings and loved ones for their

supports. Unreserved thanks to our project supervisor – Dr Emmanuel Ikechukwu Nnamonu for

doing a thorough supervision.

Thanks to our HoD – Mrs. C. I. Okenyi and all lecturers in the Department of Biology, FCE,

Eha-Amufu for their supports.

TABLE OF CONTENTS PAGE

Title page
Approval page
Dedication
Acknowledgement
Table of content
Abstract
CHAPTER ONE: INTRODUCTION
CHAPTER TWO: LITERATURE REVIEW
CHAPTER THREE: RESEARCH METHODOLOGY
CHAPTER FOUR: RESULTS
CHAPTER FIVE: DISCUSSION, CONCLUSION AND RECOMMENDATION
REFERENCES

ABSTRACT
The present study is designed to investigate the nephron-toxic effects of artemether lumefantrine
and chloroquine in albino rats. Sixty adult male albino rats, 12–13 weeks of age, weighing 156 –
179 g were procured and used for this study. The study adopted the experimental design. It was a
randomized complete block design with each group replicated 3 times (4 rats per replicate). The
rats were assigned into five groups of twelve rats per group (1. CONTROL GROUP (CONTL
GRP), 2. HIGH DOSE Artemether Lumefantrine (HD ARTEM LUMF. 4/24 mg/ml), 3. LOW
DOSE Artemether Lumefantrine (LD ARTEM LUMF. 2/12 mg/ml), 4. HIGH DOSE
Chloroquine (HD CHLQN. 20 mg/ml) and 5. LOW DOSE Chloroquine (LD CHLQN. 10
mg/ml)). Rats in the Control group were administered equivalent volume of placebo (distilled
water) according to body weight. Treatment was done daily, lasted for 3 days. Administration
was orally using plastic syringes attached to metal oropharyngeal cannula. A similar trend was
observed on the effects of artemether lumefantrine and chloroquine on nephrotoxicity after a 3-
day treatment in normal albino tars. Both high (4/24 mg/ml) and low (2/12 mg/ml) doses of
artemether lumefantrine caused no significant effect (p > 0.05) on urea and creatinine as
compared with the control.
Similarly, the two doses (20 mg/ml & 10 mg/ml) of chloroquine administered showed no
significant effect (p > 0.05) on urea and creatinine as compared with the control. Conclusively,
the 3-Day treatment conducted with artemether lumefantrine and chloroquine on nephrotoxicity
in albino rats caused no significant effect on the nephrotoxicity indices investigated. Both high
and low doses of artemether lumefantrine chloroquine caused no significant effect (p > 0.05) on
urea and creatinine as compared with the control.
Keywords: Artemether-Lumefantrine, Chloroquine, Nephrotoxicity, Effects, Rats
 CHAPTER ONE

INTRODUCTION

Background of the study

Nigeria bears more than a quarter of the global burden of malaria (WHO, 2017). Nationally, 97%

of the population are at risk of the disease (NPC & ICF International, 2014). The result is that

malaria accounts for an estimated 60% of out-patient hospital visits, 30% of hospital admissions

and 11% of maternal mortalities in the country (Noland et al., 2014). Malaria also has a

deteriorating effect on the economy as an estimated 132 billion Naira (700 million dollars) is lost

due to treatment costs, prevention and other indirect costs (WHO, 2012).

To reduce the malaria burden, the World Health Organization (WHO) recommends use of

artemisinin combination therapy (ACT), for uncomplicated malaria that is confirmed with either

microscopy or rapid diagnostic test (RDT), in a bid to reduce the misuse of ACT. Chloroquine is

also among the frontline treatment for malaria (Awoleye & Thron, 2016). Researches have

reported some deleterious effects of anti-malaria drugs.

Muheet et al. (2014) reported that the use of chloroquine for longer periods requires strict

monitoring as chronic usage may lead to the development of the many detrimental effects in the

host. Ofem et al. (2013) reported that administration of chloroquine and coartem for 3 days did

not significantly altered the levels of RBC, Hb, PCV, total & differential WBC, platelet count

and platelet indices, but led to significant reductions in MCV and MCH in chloroquine recipient

(60.80 ±0.98fL and 19.14 ±0.31pg) compared with control (68.64 ±2.12fL and 20.80 ±0.60pg;

p<0.05) and coartem (68.16 ±1.73fL and 20.36 ±0.14pg; p<0.01) groups respectively. However,

administration of these drugs for 7 days caused significant reduction in RBC, Hb and PCV in

coartem recipients compared with control (p<0.05) and chloroquine (p<0.01) groups. RDW was
also significantly reduced in chloroquine recipients. In conclusion, administration of coartem and

chloroquine at their recommended doses and durations would not pose any deleterious effect on

haematological parameters in rats.

Ijeomah et al. (2016) reported that Artemether Lumefantrine and Artesunate Amodiaquine

significantly (p<0.05) decreased white blood cell count in all treated groups, but a decrease in

haemoglobin concentration which was only significant (p<0.05) with the group treated 5.71 mg /

15.14 mg/kg AA. Red blood cell count decreased in groups treated with 1.43 mg / 3.86 mg AA,

0.57 mg / 3.43 mg AL, 1.14 mg/ 6.86 mg AL and 2.28 mg / 13.72 mg AL and this decrease was

significant (p<0.05) only for the group treated with 2.28 mg / 13.72 mg AL. There was a non-

significant (p>0.05) increase in hematocrit for groups III and IV but a non-significant (p>0.05)

decrease was observed for groups VI and VII. Red cell indices were observed to decrease but

non-significantly except red cell distribution width which was observed to increase significantly.

Despite the fact that toxicity of anti-malaria drugs has been reported, there is a dearth of

literature on the nephron-toxic effects of artemether lumefantrine and chloroquine in normal

albono rats. Therefore, the present study is designed to investigate the nephron-toxic effects of

artemether lumefantrine and chloroquine in albino rats.

Statement of the problem

It has been documented that Nigeria bears more than a quarter of the global burden of malaria.

Nationally, 97% of the population Nigerians are at risk of the disease. The result is that malaria

accounts for an estimated 60% of out-patient hospital visits, 30% of hospital admissions and

11% of maternal mortalities in the country. Malaria also has a deteriorating effect on the

economy as an estimated 132 billion Naira (700 million dollars) is lost due to treatment costs,
prevention and other indirect costs. This high-profile disease burden depicts that there are factors

that predisposes Nigerians to constant malaria attacks.

Consequent to this high prevalence of malaria in our region, most persons often take anti-malaria

drugs with/without doctors’ prescription. Majority they do this are ignorant of the possible toxic

effects of anti-malaria drugs to essential organs and tissues in the body.

More so, there a dearth of literature on the evaluation of short-term nephro-toxic effects of

artemether lumefantrine and chloroquine in albino rats.

General Objective

To evaluate of short-term nephro-toxic effects of artemether lumefantrine and chloroquine in

albino rats.

Specific Objectives

This study was designed to:

i. Determine the short-term nephro-toxic effects of artemether lumefantrine and

chloroquine in albino rats

ii. Determination the short-term nephro-toxic effects of chloroquine in albino rats.

Purpose of the study

The purpose of this research is to investigate the short-term nephro-toxic effects of artemether

lumefantrine and chloroquine in albino rat. To do this, this study will determine short-term

nephro-toxic effects of artemether lumefantrine and chloroquine in albino rats and the short-term

nephro-toxic effects of chloroquine in albino rats.

Significance of the study

The study will serve as a resource base or reference point to medical practitioners, public health

workers especially those serving in the rural settlements, researchers, teachers and students of

biological and medical sciences.

Families, couples especially those still at the stage of child bearing and pregnant women will be

practically aided by the findings of this study.

Practically, the findings of this research would also enrich the knowledge and understanding of

the health ministries, NGOs and policy makers by serving as a guide to them in their efforts in

ensuring healthy living of the public.

Scope of the study

This study is limited to evaluation of the short-term nephro-toxic effects of artemether

lumefantrine and chloroquine in albino rats.

 CHAPTER TWO

LITERATURE REVIEW

Empirical review

Combination of artemether and lumefantrine

With the combination of artemether and lumefantrine, no evidence of mutagenicity was detected.

In the micronucleus test myelotoxicity was seen at the dose levels of 500, 1000 and 2000 mg/kg

(as to be expected), but recovery was almost complete within 48 hours. In rat reproductive

studies, no teratogenicity was observed, but materno- and embryotoxicity occurred at 60 mg/kg.

The same was seen in rabbits with a dose of 175 mg/kg, but not at 105 mg/kg. With lumefantrine

alone at doses of up to 1000 mg/kg no materno-, embryo- or foetotoxicty or teratogenicity was

observed in rats and rabbits. The same applies to artemether in rabbits at doses up to and

inclusive of 25 mg/kg, but at 30 mg/kg materno-, embryo- and foetotoxicty were observed. In

rats 10 mg/kg showed the same effect. There was no teratogenicity at any dose level.

Carcinogenicity studies were not conducted. Data from the manufacturer (WHO, 2002) reported

that though no animal carcinogenicity studies were carried out, animal studies of coartem®

showed no evidence of mutagenicity but at very high doses, coartem, caused impairment of

fertility by reducing pregnancy rates, increasing the number of dead fetuses, early resorptions

and post implantation losses as well

as causing decrease in sperm motility and 100 % abnormal sperm cells. Other artemisinins are

known to be embryotoxic in animals. Reproductive toxicity studies with artemisinin derivatives

(e.g., artesunate) demonstrated increased post-implantation loss and teratogenicity (a low

incidence of cardiovascular and skeletal malformations) in rats and rabbits. Similar findings were

not seen in animal reproductive studies using artemether (WHO, 2002). Studies in dogs and rat
have shown that intramuscular injections of artemether resulted in brain lesions. Changes

observed mainly in brainstem nuclei included chromatolysis, eosinophilic cytoplasmic

granulation, spheroids, apoptosis, and dark neurons. Lesions were observed in rats dosed with

Artemether at 25 mg/kg for 7 or 14 days and dogs dosed at 20 mg/kg for 8 days or longer, but

lesions were not observed after shorter courses of drug or after oral dosing (Novartis

Pharmaceuticals Corporation, 2009). Lumefantrine has a very low acute and subacute toxicity in

all animal models investigated. No death was observed at the maximum applicable dose of 2000

mg/kg.

Drug induced nephrotoxicity

Drug induced nephrotoxicity is the poisonous effect of drugs and other chemical substances on

the kidneys. There are various forms of toxicity (Galley, 2000), which should not be confused

with the fact that some medications have a predominantly renal excretion and need their dose

adjusted for the decreased renal function (e.g., heparin). The nephrotoxic effect of most drugs is

more profound in patients who already suffer from renal impairment.

Mechanisms of drug induced nephrotoxicity

Drug-induced renal failure is a well-recognized phenomenon; although the incidence of drug

induced renal disease remain uncertain. However, there are suggestions that between 5 to 20

percent of cases of acute renal failure can be directly attributed to drugs and chemicals, although

minor damage may pass undetected (Ashley, 2004). Some drugs may affect renal function in

more than one way and as such cause different types of drugs induced nephrotoxicity.

Drug-induced renal disease is common and responsible for a variety of pathological effects on

the kidney, many of which are potentially recoverable. The main types of renal injury
predominantly involve the tubules and interstitium, leading to acute tubular injury and necrosis,

or interstitial nephritis with inflammatory tubular injury (McWilliam, 2007).

Aminoglycoside antibiotics, β-lactam antibiotics and non-steroidal anti-inflammatory agents are

common offenders. Other types of renal injury are related to vascular damage and more rarely

glomerular injury. Thrombotic microangiopathy is one of the most common types of acute

vascular injury, whereas more chronic vascular changes leading to ischemic fibrosis occur with

long-term therapy with calcineurin inhibitors and analgesics (McWilliam, 2007). Knowledge of

the drug history and possible nephrotoxic effects is crucial in renal biopsy interpretation for

identifying drug-related renal disease. Medications cause renal failure through a variety of

mechanisms. Hemodynamic renal failure may result from drugs that reduce renal prostaglandins

and hence renal blood flow and glomerular filtration rate. A relatively new group of drugs with

this potential is the cyclooxygenase-2 selective inhibitors.

Direct renal tubular toxicity has also been described with a number of new medications with

unique effects on the epithelial cells of the kidney. These include the antiviral agents: cidofovir,

adefovir, and tenofovir as well as the bisphosphonate pamidronate. Additionally, crystal

deposition in the kidney may promote the development of renal failure. Several different drugs

have been described to induce crystal nephropathy, including the antiparasitic drug sulfadiazine,

the antiviral agent acyclovir, and the protease inhibitor indinavir (Perazella, 2003).

Finally, an unusual form of renal failure characterized by swollen, vacuolated proximal tubular

cells can develop from hyperosmolar substances. Agents recently described to induce an osmotic

nephrosis include intravenous immunoglobulin and the plasma expander hydroxyethyl starch

(Perazella, 2003).
The kidneys provide the common pathway for the excretion of many drugs and their metabolites,

and hence are frequently subjected to high concentrations of potentially toxic substances. Drugs

and their metabolites are taken up selectively and concentrated by the renal tubular cells before

excretion into urine, so high intracellular concentrations are attained, particularly in the renal

medulla, which has relatively little vasculature compared with the cortex. As a result, direct toxic

damage occurs, generally affecting the renal, tubular cells and renal papillae. Nephrotoxicity of

this type tends to be dose dependent. Many groups of drugs can cause renal damage, and these

effects are accentuated in patients with preexisting renal impairment (Ashley, 2004).

Chloroquine effects

The results obtained showed a significant increase in protein levels of the gastrocnemius muscle

(P < 0.001), brain (P <0.001) and spleen (P < 0.05). The total lipid content of both muscle and

brain showed a highly significant increase (P < 0.001) while the cholesterol level was increased

significantly (P < 0.05) only in the spleen. Ascorbic acid also exhibited a significant increase (P

< 0.001) in muscle. Thus, the use of chloroquine for longer periods requires strict monitoring as

chronic usage may lead to the development of the many detrimental effects in the host (Saifi et

al., 2014). In the brain of treated mice, a significant (P < 0.001) increase in protein level was

registered after 45 days of exposure to chloroquine as compared with the control group.

However, the cholesterol level did not increase in the treated group. The most markedly affected

parameter was the total lipid content where a highly significant increase (P < 0.001) was

recorded after 45 days of exposure when compared with the control group. Chloroquine

treatment significantly increased protein content (P < 0.05) compared with the control group.

The spleen cholesterol level was also affected and it increased significantly (P < 0.05) compared

with the control group after 45 days of treatment. Oral administration of chloroquine for 45 days
produced a significant increase (P < 0.001) in the protein content, total lipid and total ascorbic

acid levels and an insignificant increase (P < 0.05) in cholesterol in the muscle of treated mice

compared with the control group (Saifi et al., 2014). Chloroquine is a potent autophagic drug that

may lead to cellular degradation of hepatocytes in the liver with the concurrent production of

vacuoles 11. Observed increases in the number of lysosomes suggest further cellular degradation.

This is accompanied by fusion of lysosomes with autophagic vacuoles resulting in the biogenesis

of new lysosomes 12. The reported accumulation of Chloroquine in lysosomes has an apparent

destabilizing effect on lysosomal membranes. Toxic manifestations appear rapidly within 1 to 3

hours after ingestion 13. Thus, information is needed about its effects on organs where the drug

accumulates so as to gain insight into the impact of the long-term administration of this drug

(Jaeger & Flesch,1994).

 CHAPTER THREE

MATERIALS AND METHODS

2.1 Materials

2.1.1 Equipment used

Rat cages equipped with drinking and feeding facilities, artemether lumefantrine and chloroquine

tablets, digital weighing balance (Metler H3O, Switzerland) and plastic syringes attached to metal

oropharyngeal cannula.

2.1.2 Procurement of drugs

Lokmal QS-Combl Artemether 80 mg\Lumefantrine 480 mg and chloroquine 250 mg

manufactured by Emzor Pharmaceutical Industries Limited Flower gate Mixed Development

Scheme, KM 1, Sagamu Benin Expressway, Makun-Sagamu, Ogun State, Nigeria was bought

from reputable pharmaceutical store.

2.1.3 Procurement and management of experimental animals

Sixty adult male albino rats, 12–13 weeks of age, weighing 156 – 179 g were procured from the

Genetics and Experimental Animal Breeding Laboratory of Zoology and Environmental Biology

Department, University of Nigeria, Nsukka were used for this investigation. The rats had no

history of drug consumption (i.e., they have not been used for any investigation). They were kept

in stainless wire rat cages equipped with drinkers and fecal collecting trays, in a clean and fly
proof experimental animal house. The rats were fed with commercial grower’s chick mash made

by Vital Feeds, Nigeria Limited and clean drinking water. They were allowed to acclimatize for

fourteen days before the start of the experiment. The rats were allowed unhindered access to food

and water. The fecal droppings in the tray were removed daily.

2.2.3 Experimental design

HD AL (4/24
mg/ml)
(n=12)

LD CHQN (10
mg/ml)
CONT. LD AL (2/12
mg/ml)
(n=12) (n=12) (n=12)

HD CHQN (20
mg/ml)
(n=12)

Figure 1. Experimental design (CONT. = Control; HD AL = HIGH DOSE Artemether

Lumefantrine; LD AL = LOW DOSE Artemether Lumefantrine; HD CHQN = HIGH DOSE
Chloroquine; LD CHQN = LOW DOSE Chloroquine)

The study adopted the experimental design. It was a randomized complete block design with

each group replicated 3 times (4 rats per replicate). The rats were assigned into five groups of

twelve rats per group (1. CONTROL GROUP (CONTL GRP), 2. HIGH DOSE Artemether

Lumefantrine (HD ARTEM LUMF. 4/24 mg/ml), 3. LOW DOSE Artemether Lumefantrine (LD

ARTEM LUMF. 2/12 mg/ml), 4. HIGH DOSE Chloroquine (HD CHLQN. 20 mg/ml) and 5.

LOW DOSE Chloroquine (LD CHLQN. 10 mg/ml)). Rats in the Control group were
administered equivalent volume of placebo (distilled water) according to body weight. Treatment

was done daily, lasted for 3 days. Administration was orally using plastic syringes attached to

metal oropharyngeal cannula.

2.2.4 Collection of blood sample

About 5 ml of the blood samples was collected from each of the anaesthetized rats using the

method described by Hoff, 2000.

Biochemical parameters

Serum samples collected from both control and treated rats were used for the estimation of

creatinine and urea levels.

Serum creatinine

Serum Creatinine was determined using the alkaline picrate method (Jaffe’s Method) (Toora &

Rajagopal, 2002) where creatinine reacts with picric acid in an alkaline medium to give an

orange-coloured complex which shows maximum absorbance at 520 nm. The intensity of the

color is proportional to the concentration of the creatinine present in the serum sample and the

results are expressed as mg/dl.

NaOH creatininepicrate
Creatinine+ picricacid= →
alkaline medium orangecolourdcomplex

In brief, to 0.5 ml of serum sample taken in a centrifuge tube, 1.5 ml of water, 1 ml of 10%

sodium tungstate and 1 ml of 2/3 N sulfuric acid were added, mixed and centrifuged at 2500 rpm

for 10 min to obtain a clear supernatant. This process precipitates the proteins from the sample. 1
ml of the supernatant was transferred into another set of labeled test tubes containing equal

quantity of (0.75 N) sodium hydroxide and 1% picric acid. The contents were mixed well and

incubated at room temperature for 15 minutes for the development of color. The intensity of the

orange colour developed was measured at 520 nm using the Hitachi spectrophotometer against

the reagent blank prepared by adding 3 ml of distilled water to 1 ml of sodium hydroxide and 1

ml of picric acid. The concentration of creatinine in the samples was determined using the

standard curve prepared by taking known concentrations of creatinine solution ranging from

0.01-2 mg/dl and processed simultaneously in the same way as for the serum sample.

Serum urea

Serum urea was determined using the diacetyl monoxime method ( Rahmatullah & Boyde,

1980), wherein urea reacts with hot acidic diacetyl monoxime in the presence of

thiosemicarbazide to produce red colored complex with maxima at 525 nm. The intensity of the

colour is proportional to the concentration of urea in the sample and the results were expressed as

mg/dl.

❑ 100 ° C
Urea+ Diacetylmonoxime redcolouredcomplex
Thiosemicarbazide

In brief, to 0.2 ml of serum sample taken in a centrifuge tube, 0.8 ml of water and 1 ml of 10%

trichloroacetic acid (TCA) were added, mixed and centrifuged at 2500 rpm for 10 min to obtain a

clear supernatant. This process precipitates the proteins from the sample. 0.1 ml of the

supernatant was transferred into another set of labeled test tubes containing 3 ml of chromogenic
reagent prepared by mixing two parts of reagent I and one part of reagent II immediately before

use. [Reagent I is acid ferric solution containing 100 ml of 85% conc. phosphoric acid, 300 ml of

95% conc. sulphuric acid, 100 mg of ferric chloride and 600 ml of distilled water. Reagent II is

Diacetylmonoxime (DAMO) - thiosemicarbazide (TSC) solution containing 500 mg of DAMO

and 10 mg of TSC in 100 ml of distilled water). The contents were mixed well and boiled in a

water bath for 5 minutes. After boiling the contents were cooled to room temperature and the

intensity of the colour developed was measured at 525 nm against a reagent blank composed of

distilled water and chromogenic reagent using a Hitachi spectrophotometer. The concentration of

urea in the samples was determined using the standard curve prepared by taking known

concentrations of urea solution ranging from 0-150 mg/dl and processed simultaneously in the

same way as for the serum sample.

2.3 Statistical Analysis

Data analysis was carried out with statistical package for social sciences SPSS, IBM Statistics

UK version 16.0 one–way analysis of variance (ANOVA). The means were separated using

Duncan’s new multiple range test while differences in the means were considered significant at

probability values less than 5 % (p < 0.05). The results were presented as mean ± SEM.
 CHAPTER FOUR

RUESULTS

Effects of artemether lumefantrine and chloroquine on urea and creatinine

A similar trend was observed on the effects of artemether lumefantrine and chloroquine on

nephrotoxicity after a 3-day treatment in normal albino tars. Both high (4/24 mg/ml) and low

(2/12 mg/ml) doses of artemether lumefantrine caused no significant effect (p > 0.05) on urea

and creatinine as compared with the control.

Similarly, the two doses (20 mg/ml & 10 mg/ml) of chloroquine administered showed no

significant effect (p > 0.05) on urea and creatinine as compared with the control.

Table 1 Effects of artemether lumefantrine and chloroquine on urea and creatinine

Groups UREA (mmol/L) CREATININE

(mmol/L)

Control 6.74 ± 0.43 a 57.60 ± 2.72 a

High Dose A/L 7.13 ± 0.17 a 60.17 ± 1.76 a

Low Dose A/L 7.61 ± 0.76 a 64.54 ± 4.13 a

High Dose 6.87 ± 0.54 a 64.54 ± 2.88 a

CHLQN

Low Dose 7.13 ± 0.48 a 61.17 ± 3.54 a

CHLQN
A/L - artemether lumefantrine; CHLQN - chloroquine
 CHAPTER FIVE

DISCUSSION, CONCLUSION AND RECOMMENDATIONS

Discussion

Study of biochemical profile of blood are commonly used as indicators to access the functional

status of the animal health and the internal environment of the organism (Rehman et al., 2006).

Urea results from the catabolism of proteins and amino acids. The biosynthesis of urea is carried

out exclusively by hepatic enzymes of urea cycle and it is majorly cleared from circulation by the

kidneys. Consequently, kidney malfunction is associated with accumulation of urea in the blood

(Lamb & Price, 2008). Creatinine is formed from spontaneous cyclization of creatine and

creatine phosphate, at a slow but constant rate and it is rapidly removed from the blood by the

kidney (Harvey & Ferrier, 2011). Measurements of serum concentrations of creatinine, urea and

uric acid are commonly used as indicators of kidney function and their conditions (Lamb &

Price, 2008).

This study evaluated the effects of artemether lumefantrine and chloroquine on level of urea and

creatinine in albino rats. A similar trend was observed on the effects of artemether lumefantrine

and chloroquine on haematological profile after a 3-day treatment in normal albino tars. Both

high (4/24 mg/ml) and low (2/12 mg/ml) doses of artemether lumefantrine caused no significant

effect (p > 0.05) on urea and creatinine as compared with the control. Similarly, the two doses

(20 mg/ml & 10 mg/ml) of chloroquine administered showed no significant effect (p > 0.05) on

urea and creatinine as compared with the control. The findings of this study tend to show that
administration of artemether-lumefantrine and chloroquine does not alter the urea and creatinine

levels suggesting that the urea cycle was not affected by the administration. This suggest that a

3-day administration of artemether-lumefantrine and chloroquine caused no harmful effect in the

excretory function of the kidney. These results points to the fact that the kidneys in the testing

animals are functionally normal and that there is no renal function impairment. Creatinine and

urea are sensitive biochemical index for assessing renal functions (Abolaji et al., 2013). Our

finding is in consonant with Abolaji et al. (2013) and at variance with Omoboyowa et al., 2018.

Conclusion

The 3-Day treatment conducted with artemether lumefantrine and chloroquine on nephrotoxicity

in albino rats caused no significant effect on the nephrotoxicity indices investigated. Both high

and low doses of artemether lumefantrine chloroquine caused no significant effect (p > 0.05) on

urea and creatinine as compared with the control.

Recommendation

We recommend that further research be conducted to reveal the long-term effects of artemether

lumefantrine and chloroquine on the nephrotoxicity in rats.

 REFERENCES

Abolaji, A. O., Eteng, M. U., Omonua, O., & Adenrele, Y. (2013). Influence of coadministration
of artemether and lumefantrine on selected plasma biochemical and erythrocyte oxidative
stress indices in female Wistar rats. Human and Experimental Toxicology, 32(2): 206–
215.

Ashley, C. (2004), Renal Failure- how drugs can damage the kidney. Hospital Pharmacist, 11,
48-53.

Awoleye, O. J. (2016). Thron C. Improving access to malaria rapid diagnostic test in Niger State,
Nigeria: an assessment of implementation up to 2013. Malaria Research and Treatment,
2,
1-13.
Galley, H. F. (2000). Can acute renal failure be prevented? J R Coll Surg Edinb., 45(1): 44-50.

Harvey, R. A., & Ferrier, D. R. (2011). Lippincott’s Illustrated Reviews: Biochemistry, 5th
edition,
Lippincott Williams and Wilkins, Philadelphia, pp. 213-214, 250-288.

Jaeger, A., & Flesch, F. (1994). Review: IPCS INCHEM Home.

Ijeomah, A. U., Ugwu, M. N., Shuaibu, S. S. (2016). The effects Artesunate Amodiaquine and
Artemether Lumefantrine on some Hematological Parameters in Healthy Male Albino
Rats. PAT, 12(2), 160-168.

Lamb, E. J., & Price, C. P. (2008). Creatinine, urea and uric acid, In: Burtis, C.A., Ashwood,
E.R.,
Bruns, D.E. and Sawyer, B.G. (eds), Tietz fundamentals of clinical chemistry, 6th
edition,
W.B. Saunders, St. Louis. pp. 363-366.

McWilliam, L. J. (2007). Drug-induced renal disease. Current Diagnostic Pathology, 13(1), 25-
31.

National Population Commission, ICF International. Nigeria Demographic and Health Survey
(2013). Abuja, Nigeria. Rockville, Maryland, USA: NPC and ICF International; 2014.

Ofem, O. E., Essien, N. M., & Okon, U. A. (2013). Effects of Chloroquine and Coartem on
 Haematological Parameters in Rats. African Journal Biomedical Research, 16, 39 - 46

Omoboyowa, D. A., Nwodo F., & Elijah J. P. (2018). Effects of Combined Treatment of
Tithonia
diversifolia and Chloroquine on Selected Organs of Chloroquine Resistant Plasmodium
yeolii Infected Mice. Asian Journal of Biological Sciences, 11(2), 58-72.

Novartis Pharmaceuticals Corporation (2009. Full prescribing information on Coartem

(artemether/lumefantrine), T2008-64/T2008-65.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022268lbl.pdf

Perazella, M. A. (2003), Drug-Induced Renal Failure: Update on New Medications and Unique
Mechanisms of Nephrotoxicity, American Journal of Medical Sciences, 325(6), 349-362.

Rahmatullah, M., & Boyde, T. R. C. (1980). Clinica. Chimica. Acta, 107, 3 −9.
Rehman, H., Ali, M., Atif, F., Kaur, M., Bhatia, K., & Raisuddin, S. (2006). The modulatory
effect
of deltamethrin on antioxidants in mice. Clinica Chimica Acta 369(1), 61-65.

Saifi, M. A., Alyousif, M. S., & Alanazi, A. D. (2014). Chloroquine: its Biochemical Effects on
Vital Tissue of Mice. Latin American Journal of Pharmacy, 33(9), 1487-91.

Toora, B. D., Rajagopal, G. (2002). Measurement of creatinine by Jaffe’s reaction. 2002, Indian.
Journal of Experimental Biology, 40, 352–354.

World Health Organization (2002). Assessment of the safety of artemisinin compounds in

regnancy: report of two informal consultations convened by WHO in 2002 roll back
malaria and UNDP/World Bank/WHO special programme for research and training in
Tropical diseases. http://www.cababstractsplus.org/abstracts/Abstract.

World Health Organization (2012). Progress and Impact Series: Focus on Nigeria. Geneva:
World
Health Organization.

World Health Organization (2017). World Malaria Report. Geneva: World Health Organization.