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Artemisinin male reproductive toxicity

Supriya Singh, Anirudha Giri, Sarbani Giri
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...
January 1, 2015: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Ana C Boareto, Juliane C Muller, Aedra C Bufalo, Giuliana G K Botelho, Samanta L de Araujo, Mary Ann Foglio, Rosana N de Morais, Paulo R Dalsenter
Artemisinin compounds are important for treating multidrug-resistant malaria; however, the possible resorption and abnormalities observed in animal reproduction studies may contraindicate artemisinin use during the first trimester. To evaluate whether artemisinin interferes with developmental outcomes at different periods of pregnancy, Wistar rats were treated by gavage with increasing doses of 7, 35 and 70 mg/kg/day from gestational day [GD] 7 to 13 or 14 to 20. Viable embryos and post-implantation losses, and progestagens and testosterone levels, were monitored in the former treatment group and pregnancy and outcomes data, post-implantation losses and male and female developmental endpoints of the offspring were evaluated in the latter treatment group...
February 2008: Reproductive Toxicology
Monica Longo, Sara Zanoncelli, Paola Della Torre, Mariagrazia Riflettuto, Francesco Cocco, Manuela Pesenti, Annamaria Giusti, Paolo Colombo, Marco Brughera, Guy Mazué, Visweswaran Navaratman, Melba Gomes, Piero Olliaro
Artemisinin derivatives are clinically effective and safe antimalarials, but are not recommended during the first trimester of pregnancy because of the resorptions and abnormalities seen in animal reproduction studies. Understanding how, when and what toxicity occurs is crucial to any assessment of clinical relevance. Previously, DHA has been shown in the rat whole embryo culture (WEC) to primarily affect primitive red blood cells (RBCs) causing subsequent tissue damage and dysmorphogenesis. To verify the primary target of DHA in vivo and to detect consequences induced by early damage on embryo development, pregnant female rats were orally treated on gestation days (GD) 9...
November 2006: Reproductive Toxicology
W Hofheinz, H Bürgin, E Gocke, C Jaquet, R Masciadri, G Schmid, H Stohler, H Urwyler
The discovery of the natural peroxides qinghaosu (arteannuin A, artemisinin) (1) and yingzhaosu A (3) from traditional Chinese herbal medicines was a major advance in the search for new antimalarials (Fig. 1). Whereas qinghaosu can be produced from natural sources and has been well studied, yingzhaosu A has never been available for full evaluation as anti-malarial. We have designed a synthesis of the novel ring system present in yingzhaosu A, the 2,3-dioxabicyclo[3.3.1]nonane and prepared a series of yingzhaosu A analogues which were tested against Plasmodium berghei in mice...
September 1994: Tropical Medicine and Parasitology
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