Abstract
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.
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Acknowledgements
The authors are grateful to the Africa Centre of Excellence for Neglected Tropical Diseases and Forensic Biotechnology, Ahmadu Bello University, Zaria, Nigeria (ACENTDFB-ABU), and management of Ahmadu Bello University, Zaria, Nigeria, for financial support and provision of critical study facilities, respectively.
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AM, ABS and LCO helped in conceptualization; AM and ABS worked in design; LCO and MB helped in laboratory experiments; MAU, LCO, AM and MB helped in data analysis; MAU and LCO helped in writing—original draft preparation; AM, ABS and MB helped in writing—review and editing; AM, ABS, LCO and MB helped in resources and AM, ABS and MAU worked in supervision. All authors approved the final version of the manuscript.
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In relation to this study, no conflicts of interest were declared by Lovina Chinyere Ogbu, Aliyu Muhammad, Mohammed Aliyu Usman, Musa Bashir and Abdullahi Balarabe Sallau.
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Ogbu, L.C., Muhammad, A., Usman, M.A. et al. Comparative cyto-genotoxicity and clastogenicity properties of traditional trypanocidal Afrormosia laxiflora and Lonchocarpus laxiflorus plants in Wistar rats. Toxicol. Environ. Health Sci. 15, 217–226 (2023). https://doi.org/10.1007/s13530-023-00175-8
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DOI: https://doi.org/10.1007/s13530-023-00175-8