ACUTE AND SUB-ACUTE TOXICITY EVALUATION OF DISULPHIDE DERIVATIVE OF DIHYDROARTEMISININ
Journal Title: World Journal of Pharmaceutical Research - Year 2017, Vol 6, Issue 1
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<0.001), but urea and creatinine were unaltered by sDHA and DHA. Additionally, both drug treatments resulted in alterations in liver-to-body weight ratio and liver microstructure. Kidney-to-body weight ratio was not affected by both drugs, but they caused mild glomerular inflammation and vascular degeneration. Furthermore, they reduced RBC, Hb, PCV, and platelet levels (p<0.001). The drugs also caused elevations in total and differential WBC counts, except basophil. The effects on all the parameters by both drugs were comparable, except on RBC, wherein sDHA induced a higher level of reduction (p<0.05). Putting the results together, both drugs have comparable toxicity profiles, although, sDHA reduces erythrocytes more and has a lower LD50.
Authors and Affiliations
Dr. Jonah Sydney Aprioku
Keywords
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