Dihydroartemisinin Photoirradiation: Reduced Antiplasmodic Activity and Toxicological Implications

Abstract

Many antimalarial drugs are photoreactive, inducing varied phototoxic reactions. Dihydroartemisinin, the active metabolite of 
all artemisinins possesses sesquiterpene ring with an endoperoxide bridge which is essential for the antiplasmodial activity, and 
is a strong site for photochemical reactions. This accelerated photochemical stability study evaluated the physicochemical and 
biological implications of photo irradiation of dihydroartemisinin. Dihydroartemisinin (0.04%w/v) in aqueous methanol solution 
(50%v/v) was irradiated for 1 hour using ICH Photostability testing guidelines at 365nm. Photoirradiated samples were analysed 
using thin layer chromatography (TLC), ultraviolet spectrophotometry (UV) and high performance liquid chromatography 
(HPLC). Antiplasmodial activity, packed cell volume (PCV), liver enzyme assay and histopathology were also determined. Photo 
irradiation of the dihydroartemisinin solution gave golden brown colour with formation of needle like crystals and two additional 
TLC spots. The UV spectra showed a broad band at 229 – 302nm and the presence of four new photodegradation products in the 
HPLC chromatogram. Significant reduction in body weights (p=0.0001), PCV (p=0.0002) and antiplasmodial properties were 
observed with the irradiated dihydroartemisinin samples. Aspartate aminotransferase and alanine aminotransferase levels of the 
mice were significantly increased. Photo irradiated samples showed various stages of hepatotoxicity; massive hepatic 
degeneration and necrosis of the liver with hyperplaxia and hemosiderin laden kupffer cells as well as multifocal lymphocytic 
infiltration. This study confirms that dihydroartemisinin has the potential of undergoing photodegradation with reduction in 
antiplasmodial activity and possible hepatotoxicity.