The role of fenugreek seed extract in alleviating pancreatic toxic effects and altering glucose homeostasis induced by acetamiprid via modulation of oxidative stress, apoptosis, and autophagy.

Acetamiprid (ACMP) is a second-generation neonicotinoid that has been extensively used in the last few years. The present study examined the toxic effects of ACMP on the pancreas and glucose homeostasis through the evaluation of histological and biochemical changes and the possible ameliorative role of fenugreek seed extract (FG). Fifty adult albino rats were divided into 5 groups: negative control, positive control, FG-treated, ACMP-treated, and ACMP + FG-treated groups by oral gavage for 12 weeks. The ACMP-treated group highlighted significant elevations in plasma glucose, glycosylated haemoglobin levels (HbA1c), serum amylase, and serum lipase, along with a decrease in plasma insulin levels. In addition, significant increases in tumour necrosis factor- alpha (TNF-α) and malondialdehyde (MDA) were associated with reductions in the levels of interleukin 10 (IL-10), glutathione peroxidase, and catalase. Moreover, glucose-6-phosphatase and glycogen phosphorylase were significantly increased, with a significant reduction in hexokinase and liver glycogen stores. These biochemical changes were associated with histological changes in pancreatic sections stained by haematoxylin and eosin, Masson stain, and Orcein stain. ACMP-treated cells showed a marked reduction in ß- cell immune reactivity to insulin, with pronounced p53, and beclin 1 immune expression. The use of FG with ACMP induced partial protection except for hexokinase and glycogen phosphorylase.

Polystyrene microplastic particles induced hepatotoxic injury via pyroptosis, oxidative stress, and fibrotic changes in adult male albino rats; the therapeutic role of silymarin.

Microplastics (MPs) have become a worldwide issue because of their persistence in marine organisms, their accumulation in the food chains, and their inevitable human exposure. Silymarin is a therapeutic agent used in the treatment of multiple liver diseases. The study aimed to explore the potential therapeutic effect of 2 weeks of silymarin treatment against the effects of two sizes of 1 and 5 µm of polystyrene microplastic particles (PS-MPs) on the liver after 6 weeks of the study period. Animals were divided into negative and positive control, silymarin group (200 mg/kg), PS-MP groups of 1 and 5 µm size (0.02 mg/kg), 1 µm size PS-MPs + silymarin group, and 5 µm size PS-MPs + silymarin group, animals were treated once daily by oral gavage. The study revealed that hepatotoxicity induced by two diameters of PS-MPs with marked destructive effects of 1 µm size greater than that of 5 µm size and the effective therapeutic role of silymarin in improving PS-MPs caused hepatotoxic injury, particularly with 5 µm PS-MPs size; through regression of liver pathology (hepatic cell lysis, inflammation, fibrotic changes, and collagen deposition), restoring ultrastructure morphology (mitochondrial destruction and accumulation of lipid droplets accumulation). It improved liver function by reducing serum AST, ALT, LDH, total cholesterol, and triglycerides. It also reduced oxidative stress by reducing serum MDA, increasing TAC, down-regulation of iNOS, and up-regulation of Nrf2 and HO-1 hepatic gene expression. Furthermore, it relieved pyroptosis by negatively regulating the expression of the NLRP3, caspase-1, and IL-1ß hepatic gene expression. The results suggested silymarin's therapeutic effects in treating PS-MPs-induced hepatotoxic injury and recommended its use as a postexposure treatment for a longer duration.

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.

Combined lead and zinc oxide-nanoparticles induced thyroid toxicity through 8-OHdG oxidative stress-mediated inflammation, apoptosis, and Nrf2 activation in rats.

A human is exposed to a chemical mixture rather than a single chemical, particularly with the wide spread of nanomaterials. Therefore, the present study evaluated the combined exposure of lead acetate (Pb) and zinc oxide-nanoparticles (ZnO-NPs) compared to each metal alone on the thyroid gland of adult rats. A total of 30 adult male albino rats were divided into four groups, group I (control), group II received Pb (10 mg/kg), group III received ZnO-NPs (85 mg/kg) and group IV co-administrated the two metals in the same previous doses. The materials were gavaged for 8 weeks. The toxicity was assessed through several biochemical parameters. Our results revealed significant body weight reduction relative to increased thyroid weights, decreased both of serum-free triiodothyronine (FT3), tetra-iodothyronine (FT4), increased thyroid-stimulating hormone (TSH), increased serum and thyroid levels of Pb and zinc, significant elevation in tumor necrosis factor-α (TNF-α), reduction in interleukin 4 (IL4), upregulation of Bax, and downregulation of Bcl-2 genes. Additionally, there was significant overexpression of nuclear factor erythroid 2-related factor 2(Nrf2), 8-Hydroxydeoxyguanosine(8-OHdG), the elevation of tissues malondialdehyde (MDA), reduction of tissues total antioxidant capacity (TAC), and disruptive thyroid structural alterations in all metals groups with marked changes in the combined metals group. In conclusion, the combined exposure of Pb and ZnO-NPs induced pronounced toxic thyroid injury, pointing to additive effects in rats than the individual metal effects through different significant changes of disruptive thyroid structural alterations related to the loading of thyroid tissues with Pb and zinc metals producing oxidative stress that mediated inflammation and apoptosis.

Maternal Δ-aminolevulinic acid dehydratase 1-2 genotype enhances fetal lead exposure and increases the susceptibility to the development of cerebral palsy.

Limited epidemiologic studies questioned the association between pre- and postnatal lead exposure and the development of cerebral palsy (CP). Moreover, the genotypes of δ-aminolevulinic acid dehydratase (δ-ALAD) in CP patients and their mothers and their association to the blood lead levels (BLLs) were not previously studied. This study aimed to evaluate the association between δ-ALAD gene polymorphism and BLL in cases of CP and their mothers. A case control study was carried out on 23 CP cases and equal number of healthy matched controls. The mothers of the included children were asked to answer a questionnaire involving the baseline clinical and demographic characteristics. Also, questionnaires were done to detect the sources of environmental lead exposure and screen lead exposure during the pregnancy period. BLL, δ-ALAD enzyme activity, and genetic analysis for ALAD G177C were done for each child and his mother. There was significant (p < 0.001) elevation of BLL in CP cases and their mothers that was positively correlated (r = 0.436, p < 0.05). There were progressive decreases in δ-ALAD activity with increasing BLL in both children and mothers (p < 0.05). There were non-significant (p > 0.05) differences between CP and the control group regarding frequency of ALAD G177C genotypes, while there was a significant (p = 0.04) increase in the frequency of ALAD 1-2 (GC) genotype in the mothers of the CP group associated with high BLL and significant decrease in δ-ALAD activity (p < 0.001). The study can indicate the significance of δ-ALAD gene polymorphism in the prenatal exposure to lead and the affection of the developing brain, pointing to the importance of controlling lead in pregnant women especially those with ALAD 1-2 genotype.