Methotrexate enhances oxidative stress, apoptosis, and ultrastructural alterations in the placenta of rat.

The chemotherapeutic drug methotrexate (MTX) is utilized to treat various malignancies. MTX exposure during pregnancy causes miscarriages, abnormalities in newborns, and developmental delays. The current study examined the placenta's sequential histopathological alterations following exposure to the MTX in pregnant rats. Twenty-four pregnant rats were assigned into; the control group and MTX group (0.2 mg/kg). MTX was given intraperitoneally on gestational days 11-12. Oxidative stress parameters were measured in placental homogenates. The placental specimens were evaluated by light, immunohistochemical (caspase-3 and vascular endothelial growth factor (VEGF)), and electron microscopic study. Malondialdehyde levels were significantly elevated by MTX, whereas glutathione peroxidase and superoxide dismutase levels were significantly reduced. The MTX group showed a marked reduction in the thickness of both the basal and labyrinth zones. Degeneration of the labyrinth zone was demonstrated. Also, giant trophoblast cells and the spongiotrophoblasts of the basal zone showed vacuolations with dark nuclei. Up-regulation of caspase-3 and down-regulation of VEGF immunoexpression were demonstrated. Ultrastructurally, disintegration of the interhemal membrane, spongiotrophoblasts with vacuolated cytoplasm and small condensed nuclei, and the giant trophoblasts with irregular nuclear outlines and vacuolated cytoplasm were demonstrated. In conclusion, MTX has profoundly altered the structure of the placenta.

Betahistine Attenuates Seizures, Neurodegeneration, Apoptosis, and Gliosis in the Cerebral Cortex and Hippocampus in a Mouse Model of Epilepsy: A Histological, Immunohistochemical, and Biochemical Study.

Epilepsy is a prevalent and chronic neurological disorder marked by recurring, uncontrollable seizures of the brain. Chronic or repeated seizures produce memory problems and induce damage to different brain regions. Histamine has been reported to have neuroprotective effects. Betahistine is a histamine analogue. The current research investigated the effects of convulsions on the cerebral cortex and hippocampus of adult male albino mice and assessed the possible protective effect of betahistine. Four groups of 40 adult male mice were organized: control, betahistine (10 mg/kg/day), pentylenetetrazole (PTZ) (40 mg/kg/ on alternate days), and Betahistine-PTZ group received betahistine 1 h before PTZ. PTZ induced a substantial rise in glutamate level and a considerable decrease in histamine level. Structural changes in the cerebral cortex and cornu ammonis (CA1) of the hippocampus were detected in the pattern of neuron degeneration. Some neurons were shrunken with dark nuclei, and others had faintly stained ones. Focal accumulation of neuroglial cells and ballooned nerve cells of the cerebral cortex were also detected. Cleaved caspase-3, glial fibrillary acidic protein, and ionized calcium-binding adaptor molecule 1 showed substantial increases, while synaptophysin expression was significantly reduced. Interestingly, these changes were less prominent in mice pretreated with betahistine. In conclusion, betahistine had shown neuroprotective properties against brain damage induced by convulsions.

The immune modulatory role of marjoram extract on imidacloprid induced toxic effects in thymus and spleen of adult rats.

Imidacloprid (IMID), one of environmental persistent neonicotinoid insecticides, has been used a long time ago and categorized from insecticide induced moderate toxicity by World Health Organization (WHO). Marjoram, is one of the most worldwide used herbs in Egypt due to its antioxidant, anti-inflammatory, anti-genotoxic, anti-mutagenic, anticoagulant, and beneficial effects. This study aimed to evaluate the protective role of marjoram extract on the immunotoxic response and oxidative stress induced by IMID in the immune lymphoid organs (thymus and spleen) of rats. Fifty adult male albino rats were divided randomly into five groups; negative and positive (distilled water) control, marjoram extract (200 mg/kg/day), IMID (22.5 mg/kg/day), marjoram extract + IMID (200 mg/kg +22.5 mg/kg) orally for 8 weeks. Marjoram pretreatment reversed reduced animals body, thymus and spleen weights attributed to IMID. It amended the significantly elevated total leukocytes, neutrophils percentage, increased immunoglobulin G and the significantly reduction of lymphocytes percentage, phagocytic activity, phagocytic index and lysozyme activity induced by IMID. Moreover, marjoram administration significantly reduced thymic and splenic gene expression of interleukin-1ß, interleukin-6, tumor necrosis factor-α and increased interleukin-10, in addition, it decreased thymic and splenic contents of malondialdehyde and restored the reduced antioxidant enzymes' activities following IMID exposure. Marjoram ameliorated IMID induced histopathological alterations in thymus and spleen and adjusted IMID immunomodulatory effects by increased the downregulation of CD4 and CD8 immune reactive cell expression. Conclusion, Marjoram has a protective role to reverse IMID immune toxic effects in thymus and spleen tissues of rats by its antioxidant, anti-inflammatory and immunomodulatory defense mechanisms.