Introduction

Artemisinin and their derivatives have been recommended for the treatment of severe and complicated malaria. They are very active anti-malaria drugs producing up to ten thousand fold reductions in parasite biomass per a sexual cycle and they reduce malaria transmissibility (white, 1999).

Many anti-malaria and antibiotic agents have been reported to have anti-fertility actions. For instance the antisteroidogenic and anti-fertility actions of quinine and chloroquine have been well documented (Meisel et. al., 1993; Adeeko and Dada, 1998). The effects of anti-malaria chloroquine on peripheral level of testosterone, gonadotrophin and sperm motility have been studied (Sehuster and Canfield, 1989). With the increased efforts in the development of more portent anti-malaria agents as a result of the challenge posed by the resistant strains of the malaria parasite, the evaluation of these anti-malaria agents for possible anti-fertility actions becomes important, this is necessary since both malaria and infertility are worldwide phenomena and the need to avoid the risk of infertility resulting from malaria chemotherapy.

In the absence of information on the reproductive toxicity of artemisinin and its derivatives the present investigation was therefore undertaken to determine in male albino rats the effect of artemisinin on certain parameters namely total sperm count, sperm motility, sperm viability and serum testosterone levels.

Materials And Methods

Animals

Experimental Design

Body And Organ Weights

Hormonal Assay

Sperm Motility, Viability, Counts And Morphology

Results

Body And Organ Weight Changes

Table 1 shows the effect of dihydroartemisinin on the body weight of rats. There was significant increase in the relative weight of testis in all the treated groups when compared with the control. All the groups showed no significant body weight again or loss throughout the experimental period.

Figure 1

Table 1: Body weight and organ weight of male rats treated with dihydroartemusinin.

Sperm Mobility

Sperm Viability

Sperm Counts

The mean epididymal sperm number was significantly reduced in all the treated groups when compared with the control. There was no significant difference in sperm counts of rats that were treated with the same does for 7 days and 21 days. However, in rats treated for 7 days, the sperm counts were significantly higher (p<0.05) in those treated with initial 2.2 mg/kg than those treated with initial 4.4 mg/kg weight (Table 2).

Figure 2

Table 2: Effect of Dihydroartenusinin on sperm Characteristics and Testosterone in Male albino Rats.

Sperm Morphology

Serum Testosterone Level

Discussion

Reduction in fertility and sterile mating recorded after treatment of male rats with Chloroquine and halofantrine have been reported to be due to impairment in sperm motility (Adeeko and Dada, 1998. Orisakwe et. al., 2003). Treatment with such antimalarial drugs result in reducing the sperm count, motility, fertility and viability, as well as increasing the amount of abnormal sperms. It has been suggested that these drugs cause androgen depletion at the targets levels. Particularly in the caudal epididymis, thereby affecting the physiological maturation of sperm (Adeeko and Dada, 1998).

The result of this present study revealed that dihydroartemisinin could cause reproductive impairment in male rats. The lack of effects on the body weight gain as well as the absence of chemical and behavioral alterations on treated animals suggest that dihydroartemisinin did not include systemic toxicity at the doses treated. However, the observed increase in relative weight of testis in this study indicates that the drug may have toxic effect on this organ. It has been reported that increase or decrease in either absolute or relative weight of an organ after administering a chemical or drug is an indicator of the toxic effect of that chemical (Simons et al, 1995).

The significant reduction in the sperm motility of rat that were treated initially with 2.2 mg/kg body weight of drugs and those treated initially with 1.1mg/kg body weight suggest that the drug was able to permeate the blood-testis barriers. The decrease in sperm motility caused by chemical agents has earlier been reported to be due to their ability to permeates the blood-testis bearer (Baldessarini, 1980) and thus, creating a different microenvironment in the inner part of the wall of the seminiferous tubules from that in its outer part (Bloom and Faweett, 1975).

Drugs that affect the testicular functions will affect the quality and quantity of spermatozoa. The mean epididymal sperm number was significantly reduced (P<0.05) in all the treated groups. There was no significant decline in serum levels of testosterone in all the treated rats when compared with the control. The significant difference in the sperm motility, viability and counts of those rats provides evidence for the significant reductions in the circulating androgen levels. Testosterone is required for the growth (Meridian et. al., 1987) and in association with follicle stimulating hormone, acts on the semniferous tubules to initiate and maintain spermatogenesis (Christensen, 1975).

In this study, the increased percentage of abnormal sperm, reduced sperm count, motility and speed, may have resulted from the alteration in the epididymal milieu, probably due to androgen deficiency consequent to the anti-androgenic property of dihydroartemisinin.

Thus, it is likely that reproductive toxicological risk would occur with the doses of dihydroartemisinin commonly consumed as anti-malaria drug by humans. However, this extrapolation should be made with caution, since the real human risk cannot be assessed on the basis of the present study. So further studies are necessary with human models to find out the effects of this drug to the testis of men.