Asian Pac J Trop Biomed 2012; 2(6): 493-495 493

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Asian Pacific Journal of Tropical Biomedicine

journal homepage:www.elsevier.com/locate/apjtb

Document heading doi:10.1016/S2221-1691(12)60083-5 襃 2012 by the Asian Pacific Journal of Tropical Biomedicine. All rights reserved.

Effect of artemether on hematological parameters of healthy and

uninfected adult Wistar rats
Osonuga IO1,Osonuga OA2, Osonuga A3*, Onadeko AA1, Osonuga AA4
1
Department of Physiology, Olabisi Onabanjo University, Ikenne Remo, Nigeria
2
Department of Pharmacology, Olabisi Onabanjo University, Ikenne Remo, Nigeria
3
School of Medical Sciences, University of Cape Coast, Ghana
4
Department of Nursing, University of Cape Coast, Ghana

ARTICLE INFO ABSTRACT

Article history: Objective: To evaluate the effect of short term artemether administration on some blood
Received 10 October 2011 parameters in adult male Wistar rats. Methods: Sixty five albino rats with body weight of
Received in revised form 25 November 2011
190-220 g were used for the four-phased study. The animals were randomly divided into five
Accepted 18 December 2011
groups. The first-four groups of 15 rats were further divided into 3 subgroups of 5 rats. The drug
Available online 28 June 2012
was administered orally at sub-optimal, therapeutic, and high doses of 25, 50 and 75 mg/kg bw,
respectively to the rats for 1 day, 2 days and 3 days. Blood samples were collected by cardio-
Keywords: puncture from the rats for hematology at the end of each phase. The last group served as control,
Artemether and they were given water ad libitum. Results: Artemether caused significant reduction (P<0.05)
Anemia of the hematological profile of the animals in a dose dependent manner. Discontinuation of the
Antimalaria drug use however showed gradual recovery of the depressed indices of the blood parameters.
Hematology Conclusions: The results suggest that artemether can induce reversible changes in hematological
Hematological profile profiles of rats by extension man. This can probably aggravate anemia when artemether is
Malaria administered to malaria patients. Hence, the study supports the use of the drug with caution
Anemic tendency especially in patients prone to anemic tendencies.

1. Introduction prophylactic and therapeutic treatment of malaria. The

recent adoption of artemisinin combined therapy as
Hematological disorders are ailments of major public treatment of choice has proven to be a potent resort for
health concern globally especially in developing countries uncomplicated malaria[6].
including Nigeria, where diagnostic facilities are not readily This therapy usually contains artemisinin or any of its
available and accessible. Anemia has been identified as the derivatives, one of which is artemether. Artemether is
commonest of them all. It also forms a common presenting a lipid soluble methylether of dihydro artemisinin with
feature of malaria and tends to worsen it[1-4]. rapid schizonticidal activity against Plamodium falciparium
Malaria is the world most important protozoan disease of parasites in blood and parasitemia clearance rate of 30-84 h[5].
which at least 300 million people are infected worldwide T oxicity studies in dogs and rats revealed dose-
yearly, causing 1.0 to 1.5 million deaths per year. It is a dependent and potentially fatal neurotoxic effects after
major cause of morbidity and mortality in West Africa. intramuscular injection of artemether at higher and
Ninety percent of malaria related deaths occur in Sub- multiple doses. These changes affect areas associated
S aharan A frica [5,6] . T he disease is endemic in sub- with vestibular, motor and auditory functions. Other toxic
Saharan Africa and children below the age of five suffer effects include embryotoxicity, gonadotoxicity, genotoxicity,
the greatest burden of the disease[6,7]. Despite efforts to immunotoxicity, cardiotoxicity, nephrotoxicity, and allergic
control the disease, malaria is among the top three deadly reactions[9-11].
communicable diseases and the most deadly tropical T herefore, this study was aimed to determine the
disease. T he disease also poses economic burden on potentially toxic effect of artemether on some blood
developing countries, cutting across all socioeconomic parameters using albino rats.
groups but with greater effect on the poor[8].
A nti-malaria drugs are drugs that are used for
2. Materials and methods
*Corresponding author: Osonuga Ayokunle, School of Medical Sciences, University of 2.1. Animals
Cape Coast, Ghana.
E-mail: [email protected]
Sixty five albino rats of the Wistar strain (190-220 g)
494 Osonuga IO et al./Asian Pac J Trop Biomed 2012; 2(6): 493-495

obtained from the Animal House of Department of Physiology, of five rats each and treated with 25, 50 and 75 mg/kg bw
University of Ibadan, Nigeria were used for the study. All of artemether, respectively for 3 days and were allowed to
the animals were males to disallow hormonal influence recover from the drug effects for another 3 days.
or any other gender related physiological factors that can Rats in group 5 (n=5) were given sterile water throughout
obliterate the pharmacological action of the drug. The the study, and served as the control in all phases.
animals were fed with standard rat cubes (Ladokun Feeds
Nig. Ltd.) and water ad libitum. Five animals were housed 2.3. Analytical procedure
per cage in the Animal House of Department of Physiology,
Olabisi Onabanjo University, Ikenne at room temperature The rats were weighed prior to treatment and at the end of
under photo-period controlled environment (12 h light: 12 h each phase differential weight gains (if any) relative to basal
darkness cycles), where they were acclimatized for a period values were obtained. The animals were anesthetized with 25%
of seven days. urethane administered at a dosage of 0.6 mL/100 g bw. Blood
sample was collected via cardio-puncture for analyses.
2.2. Experimental procedure Hematology was done according to standard methods[12].

The study was a four-phased study involving 65 albino 2.4. Statistical analysis
rats randomly divided into five groups. T he first-four
groups contained fifteen rats in each group. The fifth group All calculations were done using the SPSS-V11 statistical
contained 5 rats and served as control. Artemether (Rhone- software package for analysis of the data. The data were
Poulene Rorer International, France) was obtained from presented as means 暲 standard deviation (SD), and statistical
Olabisi Onabanjo University Health Center, Ago-Iwoye, analyses were carried out using the Student’s t-test and
Nigeria. The drug was administered orally at sub-optimal, ANOVA. Differences were considered to be of statistical
therapeutic, and high doses of 25, 50 and 75 mg/kg bw, significance at an error probability of less than 0.05 (P<0.05).
respectively to the rats for 1 day, 2 days and 3 days. Approval
for the use of the rats was obtained from the departmental
committee on the ethical use of animals. 3. Results
Rats in group 1 (n=15) were divided into three subgroups
of five rats each and treated with 25, 50 and 75 mg/kg bw of T here was no significant change in body weights of
artemether, respectively for 1 day. artemether treated rats when compared with the controls
Rats in group 2 (n=15) were divided into three subgroups ( data not shown ) . T his trend was also observed in the
of five rats each and treated with 25, 50 and 75 mg/kg bw of recovery group.
artemether, respectively for 2 days. There was significant reduction in all the hematological
Rats in group 3 (n=15) were divided into three subgroups parameters measured after the administration of artemether
of five rats each and treated with 25, 50 and 75 mg/kg bw of at the various dosages (Table 1-4). Drug withdrawal resulted
artemether, respectively for 3 days. in gradual restoration of the hematological values.
Rats in group 4 (n=15) were divided into three subgroups

Table 1
Blood parameters of experimental animals in 1 day treatment (mean暲SD) (n=5).
Groups Dosages (mg/kg bw) PCV (%) Hb (暳 10 g/L) WBC (10 /L) RBC (10 /L)
9 12

Control Sterile water 43.07暲0.35 14.00暲0.20 6.45暲0.18 7.02暲0.20

Sub-optimal 25 40.67暲0.50* 13.03暲0.25* 4.90暲0.13* 6.54暲0.22*
Therapeutic 50 39.33暲0.39* 12.60暲0.19* 4.50暲0.15* 6.40暲0.17*
High 75 38.66暲0.44* 12.10暲0.12* 3.20暲0.12* 6.01暲0.19*
PCV: Pack cell volume; Hb: Hemoglobin concentration; WBC: White blood cell count; RBC: Red blood cell count; *: P<0.05 as compared with the
control.

Table 2
Blood parameters of experimental animals in 2 days treatment (mean暲SD) (n=5).
Groups Dosages (mg/kg bw) PCV (%) Hb (暳 10 g/L) WBC (10 /L) RBC (10 /L)
9 12

Control Sterile water 43.07暲0.35 14.00暲0.20 6.45暲0.18 7.02暲0.20

Sub-optimal 25 39.66暲0.25* 11.60暲0.45* 4.70暲0.14* 6.40暲0.14*
Therapeutic 50 36.33暲0.22* 10.70暲0.26* 3.50暲0.12* 6.10暲0.20*
High 75 33.66暲0.48* 9.00暲0.20* 2.80暲0.19* 5.50暲0.15*
PCV: Pack cell volume; Hb: Hemoglobin concentration; WBC: White blood cell count; RBC: Red blood cell count; *: P<0.05 as compared with the
control.

Table 3
Blood parameters of experimental animals in 3 days treatment (mean暲SD) (n=5).
Groups Dosages (mg/kg bw) PCV (%) Hb (暳 10 g/L) WBC (10 /L) RBC (10 /L)
9 12

Control Sterile water 43.07暲0.35 14.00暲0.20 6.45暲0.18 7.02暲0.20

Sub-optimal 25 35.66暲0.25* 11.00暲0.45* 4.15暲0.10* 6.30暲0.12*
Therapeutic 50 33.33暲0.22* 10.40暲0.26* 3.17暲0.12* 5.98暲0.15*
High 75 30.00暲0.24* 9.00暲0.20* 2.50暲0.19* 4.90暲0.10*
PCV: Pack cell volume; Hb: Hemoglobin concentration; WBC: White blood cell count; RBC: Red blood cell count; *: P<0.05 as compared with the
control.
 Osonuga IO et al./Asian Pac J Trop Biomed 2012; 2(6): 493-495
495
Table 4
Blood parameters of experimental animals in 3 days treatment and 3 days recovery (mean暲SD) (n=5).
Groups Dosages (mg/kg bw) PCV (%) Hb (暳 10 g/L) WBC (10 /L) RBC (10 /L)
9 12

Control Sterile water 43.07暲0.35 14.00暲0.20 6.45暲0.18 7.02暲0.20

Sub-optimal 25 37.66暲0.40* 11.50暲0.10* 6.00暲0.14* 6.37暲0.12*
Therapeutic 50 35.66暲0.25* 11.30暲0.46* 4.93暲0.19* 6.19暲0.15*
High 75 31.33暲0.20* 9.50暲0.20* 4.12暲0.10* 4.95暲0.14*
PCV: Pack cell volume; Hb: Hemoglobin concentration; WBC: White blood cell count; RBC: Red blood cell count; *: P<0.05 as compared with the
control.
Asian Pac J Trop Dis 2011; 1: 232-234.
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