The antimalarial agent artesunate causes sperm DNA damage and hepatic antioxidant defense in mice

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2015-01, Vol.777, p.1-6
• Main Authors: Singh, Supriya, Giri, Anirudha, Giri, Sarbani
• Format: Article
• Language: English
• Subjects: Animals; Antimalarials - toxicity; Antioxidants; Artemisinins - toxicity; Artesunate; Blood-Testis Barrier - drug effects; Comet Assay; Deoxyribonucleic acid; DNA; DNA damage index, Lipid peroxidation; DNA Fragmentation - drug effects; Drug Administration Schedule; Epididymis - drug effects; Glutathione - metabolism; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - metabolism; Malaria; Male; Mice; Prescription drugs; Reduced glutathione; Rodents; Sperm; Sperm Count; Spermatozoa - cytology; Spermatozoa - drug effects; Spermatozoa - metabolism; Superoxide dismutase; Superoxide Dismutase - metabolism; Testis - cytology; Testis - drug effects; Testis - metabolism
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2014.11.001

•Artesunate induced significant increase in sperm head abnormality in mice.•There was significant reduction in host antioxidant defence and increase in lipid peroxidation.•In the short term, effects are apparent due to sperm membrane lipid peroxidation.•The long-term effects are due to DNA damage caused to spermatogonial cells. Artesunate is an artemisinin derivative effective against multidrug resistant malaria. We analyzed the effects of artesunate 40mg/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.