FETAL HEPATORENAL TOXICITY OF ARTEMETHER/LUMEFANTRINE (COARTEM®) IN SECOND TRIMESTER OF PREGNANCY IN ALBINO RATS

*Umoh I. U., Ekanem T. B., Eluwa M. A. and Bassey U. E.

ABSTRACT

The effect of artemether/lumefantrine (Coartem®) administration in second trimester of pregnancy on the morphometric indices of rat fetuses, fetal liver and kidney as well as amniotic alpha fetoprotein was investigated in this study. Twenty (20) pregnant albino Wistar rats were divided into 4 groups of 5 animals per group and used for the study. Group 1 served as control and received no drug treatment. Group 2 received 8mg/kg (therapeutic dose) of coartem while Groups 3 and 4 received 16mg/kg and 24mg/kg of coartem respectively. The drug was administered twice daily for three days being its normal therapeutic regimen. The animals were sacrificed on the 20th day of pregnancy under chloroform anaesthesia, fetuses delivered through uterotomy and assessed for morphological deformities. Fetal liver and kidney were harvested and evaluated for histopathology. Amniotic fluid was obtained and used to assay for alpha fetoprotein (AFP) levels. A significant (P < 0.05) dose dependent decrease in fetal body weight, crown rump length was observed in the fetuses of the treated groups when compared to the control. Significant decrease in amniotic alpha fetoprotein was also observed in Group 2 and 4 while the AFP level in Group 3 was significantly increased (P < 0.05). The histology of fetal liver revealed mild to severe alterations in cellular cytoarchitecture and features such as hepatocytic necrosis, dilated central veins and sinusoidal spaces were observed in the treatment groups. Sections of the fetal kidney showed atrophic and degenerated glomeruli as well as tubular necrosis whose severity increased with increasing dose of coartem. The study has shown that artemether/lumefantrine is toxic to fetal liver and kidney when administered to pregnant albino wistar rats in second trimester and fetal growth was also reduced significantly.

Keywords: Artemether/Lumefantrine, Coartem, Fetal hepatorenal toxicity, pregnancy.