Obiettivo
Artemisinin based antimalarial drug combinations are recommended for the treatment of P.falciparum malaria infections throughout all malarial endemic areas of the world and in all populations, including women of child bearing age. The studies planned in this collaborative project are central to assessing the potential hazard posed by these drugs to the developing human foetus and thereby making evidence based recommendations on the risk:benefit of these drugs. Although clinical experience to date indicates the artemisinins to be safe, the area of reproductive toxicology demands special consideration. Data from the Chinese literature and our own studies confirm that the artemisinins are embryotoxic and potentially teratogenic in animal species at drug doses within the human therapeutic range. Based on over ten years of investigating the pharmacology of these drugs we have developed a hypothesis which can explain these teratogenic effects. Our hypothesis is based on the generation of reactive oxygen species (ROS) from cleavage of the artemisinin peroxide bridge and consequent embryofoetal damage to key biological macromolecules. Our hypothesis draws on parallels with the metabolic activation and teratogenic effects of the other established teratogens such as phenytoin
Campo scientifico
- medical and health scienceshealth sciencesinfectious diseasesmalaria
- medical and health sciencesbasic medicinephysiologypathophysiology
- medical and health sciencesclinical medicineobstetrics
- medical and health sciencesbasic medicinetoxicology
- medical and health sciencesbasic medicinepharmacology and pharmacy
Parole chiave
Invito a presentare proposte
FP7-HEALTH-2007-A
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Meccanismo di finanziamento
CP-FP - Small or medium-scale focused research projectCoordinatore
L35QA LIVERPOOL 3
Regno Unito