The antimalarial agent artesunate causes sperm DNA damage and hepatic antioxidant defense in mice.
Artesunate is an artemisinin derivative effective against multidrug resistant malaria. We analyzed the effects of artesunate 40 mg/kg b.w. as a single dose (ART1) or 13.3mg/kg b.w. for 3 days at 24h intervals (ART2) on mice spermatozoa at morphological and molecular level, and hepatic antioxidant status following 24h and 35 days following exposures in vivo. Artesunate significantly reduced epididymal sperm count and increased the frequency of sperms with abnormal head morphology following 24h of exposure. Comet assay analysis revealed significant increase in DNA strand breaks in spermatozoa evidenced by about 3-fold increase in comet tail DNA and up to 10-fold increase in Olive tail moment following 35 days of artesunate treatment. The damage index was significantly higher in the treated groups (40.27 ± 6.62 and 37.07 ± 5.35 for ART1 and ART2 respectively) as compared to the control group (16.13 ± 3.21) indicating the genotoxic effect of artesunate. The significant reduction in GSH, SOD and increase in lipid peroxidation indicate involvement of oxidative mechanisms in artesunate induced toxicity in mice. The present study suggests that artesunate has the potential to breach the testis-blood barrier and cause toxicity to male germ cells which may have implications in male reproductive toxicity.
Molecular Cytogenetics Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788 011, India.
Supriya
S
Singh
Environmental Toxicology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788 011, India.
Anirudha
A
Giri
Molecular Cytogenetics Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar 788 011, India. Electronic address: girisarbani@yahoo.com.
Sarbani
S
Giri
D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D037621:Artemisinins / Q000633:toxicity*; D000077332:Artesunate; D001814:Blood-Testis Barrier / Q000187:drug effects; D020552:Comet Assay; D053938:DNA Fragmentation / Q000187:drug effects*; D004334:Drug Administration Schedule; D004822:Epididymis / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D013076:Sperm Count; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D013482:Superoxide Dismutase; D005978:Glutathione
Artesunate; Comet assay; DNA damage index, Lipid peroxidation; Reduced glutathione; Superoxide dismutase