Background: This research was designed to investigate ovarian and uterine gene transcriptional responses to artesunate in female rats. Materials and Methods: Female rodents (120 – 140 g) numbering ten were designated for this study. Artesunate (1.43 mg/kg) was given by gavage to the rodents for 50 days. The method of RT-PCR was employed to investigate the expressions of p53, Bcl-2, SOD, aromatase and IL-1β in the ovaries and uteri. Histopathological analyses of the uteri and ovaries were also done. Graphics were generated as average +/- SEM with Graph-pad Prism (version 8.0). Results: The p53 and aromatase expressions were significantly (p<0.05) down-regulated, while the Bcl-2 and IL-1β expressions were upregulated significantly (p<0.05) in the artesunate treated rats’ ovaries relative to their controls. In addition, the p53, Bcl-2, SOD and IL-1β expressions were up-regulated significantly (p<0.05), but the aromatase expression was significantly (p<0.05) down-regulated in the artesunate treated rats’ uteri relative to their controls. Furthermore, the histopathological analyses indicated severe congested (hemorrhagic) ovarian medulla as well as expanded lumens of the endometrial glands. Conclusion: Conclusively, this study has suggested that artesunate inhibited apoptosis and steroidogenesis, but induced inflammation and carcinogenesis in rats’ ovaries. In addition, it probably inhibited apoptosis, superoxide radicals (oxidative stress) and steroidogenesis; but also induced inflammation and carcinogenesis in rats’ uteri. Furthermore, it is also probably toxic to the ovaries and uteri at histological level
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