| Abstrakt: |
Objective: Expensiveness of trypanocides triggered the use of plants decoction as a therapeutic option after safety validation. We evaluated the cyto-genotoxic and clastogenic effects of antitrypanosomal plants; Lonchocarpus laxiflorus (LL) and Afrormosia laxiflora (AL) and their impact on hepatic metabolomics in Wistar rats. Methods: The IC50 was determined based on malondialdehyde (MDA) level (ex vivo). This was followed by lactate dehydrogenase (LDH), 8-hydroxy-2′-deoxyguanosine (8OHDG), DNA fragmentation (DF) and micronucleated polychromatic erythrocytes (MNPCEs) determinations. Hepatic metabolites of exposed rats to the said plants' extracts were identified by LC–MS coupled with a positive control group treated with sodium arsenite (SA). Results: The IC50s of LL and AL are 2.545 and 5.693 µg/ml, respectively, for liver tissue and 4.440 and 5.877 µg/ml, respectively, for bone marrow tissue. In bone marrow tissue, low cyto-genotoxicity potentials based on LDH and 8OHDG levels as compared with SA were observed. At in vivo level, we observed significant (p < 0.05) reduction of MDA, LDH, 8OHDG, DF and MNPCEs levels relative to SA-treated rats. Based on metabolomics, tyrosine, sphingolipid and glycerophospholipid metabolic pathways were likely activated in SA-treated group and shut down in LL- and AL-treated groups with concomitant stabilization of sphingolipid metabolism in SA + LL- and SA + AL-treated rats. However, AL-treated group showed activation of phenylalanine metabolism. Conclusion: Altogether, AL depicts insignificant (p > 0.05) cyto-genotoxicity and ability to cause chromosomal breakage ex vivo and in vivo, indicating that decoction of AL appears to be safe for the treatment of human trypanosomiasis. [ABSTRACT FROM AUTHOR] |
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