Abstract

ACUTE AND SUB-ACUTE TOXICITY EVALUATION OF DISULPHIDE DERIVATIVE OF DIHYDROARTEMISININ

Imoh Emmanuel Udoh, Jonah Sydney Aprioku*, Iyeopu Minakiri Siminialayi

Abstract

Dihydroartemisinin (DHA), the active metabolite of artemisinins, possesses anticancer activity but its usefulness may be limited by its short half-life. Recently, a persulphide (or disulphide) derivative of DHA (sDHA) has been synthesized with the aim of extending its halflife. This study evaluated the acute and sub-acute toxicity profile of sDHA in comparison with the parent drug, DHA in Sprague-Dawley rats. LD50 of DHA and sDHA were determined using Lorke’s method. Thereafter, 0, 10, 20 and 30% of their LD50 were administered i.p., once daily for 28 days to different groups of rats (n=6 per group). Body weights, as well as hepatic, renal and hematological indices were evaluated. LD50 values obtained for sDHA and DHA were 374.17 and 574.46 mg/kg i.p., respectively. Body weights were unaffected, serum levels of AST, ALT and ALP were elevated (p

Keywords: Dihydroartemisinin, endodisulphide, endoperoxide, Lorke’s method