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Eighty pregnant female mice were alloted among 16 groups. The animals were given intraperitoneal injection equalized to the therapeutic doses used for human. Indomethacin was given (25, 75 mg/kg b.wt.) and cyclosporine-A was given (5, 10, 15 mg/kg b.wt.). They induced significant increase in fetal resorption and significant decrease in fetal body weight. Also, reduction in the sizes of the skeletons of embryos was observed. Dosage of 150 mg/kg b.wt. of indomethacin was the lethal dose to dams. Various chromosomal aberrations in maternal bone marrow cells and embryos cells and mitotic activity were recorded, quantitated and statistically analyzed. Indomethacin (75 mg/kg) induced more chromosomal aberrations in both pregnant females as well as fetuses than the lower dose (25 mg/kg). Cyclosporine-A (15 mg/kg b.wt.) induced an increase in chromosomal aberrations in bone marrow cells of female mice than lower dose (5, 10 mg/kg b.wt.), while no significant differences were observed between the (5, 10 mg/kg) doses. Also, cyclosporine-A (15 mg/kg) showed highly significant increase in chromosomal aberrations in embryos than medium (10 mg/kg) or lower doses (5 mg/kg).

Background The excessive exposure to silver nanoparticles (Ag-NPs) has raised concerns about their possible risks to the human health. The brain is a highly vulnerable organ to nano-silver harmfulness. The aim of the current work was to evaluate the impacts of Ag-NPs exposure on the cerebellar cortex of rats especially changes at the ultrastructural and molecular levels. Methods Forty adult male albino rats were assigned to: control, vehicle control, Ag-NP-exposed groups (at doses of 10mg and 30mg/kg/day). Cerebellar cortex samples were processed for light and electron microscope examinations. Immunohistochemical localization of c-Jun N-terminal kinase (JNK), nuclear factor kappa beta (NF-κB) and Calbindin D28k (CB) proteins was performed. Tissue homogenates were prepared for analysis of gene expression of DNA damage inducible transcript 4 (Ddit4), flavin containing monooxygenase 2 (FMO2) and thioredoxin-interacting protein (Txnip). Serum levels of inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also measured. Results Ag-NPs exposure resulted in activation of apoptosis cascades coupled with stimulation of oxidative stress and inflammation pathways. This was evident by the upregulation of Ddit4 gene expressions and JNK protein immune expressions. Alterations of redox homeostasis were verified by enhancement of Txnip and FMO2 gene expressions, favoring the activation of inflammatory responses by increasing NFκB immune expressions and serum inflammatory mediator levels. Another considerable cytotoxic effect was the reduction of CB immune expressions, the crucial regulator of intracellular calcium level. Conclusion Ag-NPs exposure provoked biochemical, cellular and molecular changes of rat cerebellar cortex in a dose-dependent manner.