Follicular Atresia and Alterations of the Estrus Cycle Induced by Artemisinin-Based Medication in the Cyclic Rat

Abstract

Malaria is a major public health scourge in many tropical countries and still accounts for considerable annual mortality. Various drugs have been used over the last several decades in its treatment with the artemisinin based drugs being the latest. This study examined the effects of these drugs on the histology of the ovaries and duration and pattern of estrous cycle in rats. Forty female cyclic rats were randomized into two-groups. The first had 5 groups and the second 3 groups consisting of animals selected for being norm cyclic. Each group had 5 animals each. They were treated with therapeutic and higher doses of Arthemeter/Lumefantrin and Artesunate brand of artemisinin, given orally for 7 and 16 days. Animals in the second group were examined daily for possible alterations of length and pattern of their estrus cycle. At the end of these periods the animals were sacrificed. Their ovaries were processes for histological examination and assays of serum anti-oxidants and MDA levels were performed. Both drugs caused marked follicular artresia, and increased cycle length from a mean of 4 to 5.3days, (p<0.05), and increased the duration of di-estrus. They also caused significant changes in serum levels of catalase and superoxide dismutase enzymes. This study shows that these medicines can cause follicular damage and alter the estrus cycle in rats. The unrestricted use of these drugs by young women must be discouraged.