Endocrine disruption and oxidative stress implications of artemether–lumefantrine combination therapy in the ovary and uterus of rats

Abstract

In the current study, we evaluated the endocrine disruption effect and oxidative stress implication of therapeutic dose of artemether–lumefantrine combination therapy on the ovary and uterus of rats. In this respect, female rats were divided into four groups: animals were per orally treated with tween 80 (control), artemether (4 mg kg−1 body weight), lumefantrine (24 mg kg−1 body weight) and artemether–lumefantrine (artemether, 4 mg kg−1 body weight and lumefantrine, 24 mg kg−1 body weight). We found that therapeutic doses of the drugs did not change the levels of ovarian hydrogen peroxide (H2O2) and malondialdehyde (MDA), but increased uterine levels of H2O2 and MDA and reduced ovarian and uterine levels of reduced glutathione. In addition, whilst ovarian glutathione peroxidase (GPx) activity reduced in the lumefantrine monotherapy group, uterine GPx increased in the artemether monotherapy as well as the artemether–lumefantrine groups. Furthermore, the drugs reduced ovarian and uterine glutathione- S-transferase and uterine superoxide dismutase activities. The drugs reduced oestrogen level, whereas follicle-stimulating hormone was reduced by lumefantrine and artemether–lumefantrine therapies. Additionally, artemether and lumefantrine monotherapies significantly increased prolactin and progesterone levels compared with the control ( p < 0.05). The results suggest that in the absence of malarial parasite infection, the drugs induced oxidative stress in the ovary and uterus and disrupt hormonal balance in the rats.