Preparation, physicochemical characterization, and bioactivity evaluation of berberine-entrapped albumin nanoparticles.

Berberine (BBR) is an isoquinoline alkaloid with several clinical therapeutic applications. Its low water solubility, absorption, and cellular bioavailability diminish BBR's therapeutic efficacy. In this study, BBR was encapsulated into bovine serum albumin nanoparticles (BSA NPs) core to reduce BBR limitations and enhance its clinical therapeutic properties. Several physicochemical characterization tools, such as Dynamic Light Scattering and Ultraviolet-Visible spectroscopic measurements, field emission transmission electron microscopy surface morphology, Fourier transforms infrared spectroscopy, thermal stability analysis, and releasing studies, were used to evaluate the BBR-BSA NPs. Compared to BBR, BBR-BSA nanoparticles demonstrated superior free radical scavenging and antioxidant capacities, anti-hemolytic and anticoagulant efficacies, and antimicrobial activities, as demonstrated by the findings of the in vitro studies. Furthermore, a stressed pancreatic rat model was induced using a high-fat, high-sucrose diet plus carbon tetrachloride injection. The in vivo results revealed that BBR-BSA NPs substantially restored peripheral glucose metabolism and insulin sensitivity. Oral administration of BBR-BSA NPs also improved pancreatic ß-cells homeostasis, upregulated pancreatic antioxidant mechanisms, inhibited oxidants generation, and attenuated oxidative injury in the stressed pancreatic tissues. In conclusion, our in vitro and in vivo results confirmed that BBR-BSA NPs demonstrated more potent antioxidant properties and restored pancreatic homeostasis compared to BBR.

Fisetin alleviates thioacetamide-induced hepatic fibrosis in rats by inhibiting Wnt/ß-catenin signaling pathway.

BACKGROUND: Liver fibrosis is a chronic wound-healing response to liver injury of various origins and represents a major health problem. OBJECTIVE: The current study endeavored to investigate the repressing effect of fisetin on hepatic fibrosis induced by thioacetamide (TAA) in rats. MATERIALS AND METHODS: Rats were injected with TAA (200 mg/kg) intraperitoneally twice per week for 6 weeks to induce liver fibrosis. Fisetin (50 and 100 mg/kg/day) or silymarin (50 mg/kg/day) were given orally on a daily basis along with TAA. Liver function parameters, oxidative stress, inflammatory and fibrogenic biomarkers as well as wnt3a, ß-catenin, glycogen synthase kinase 3 (GSK-3ß) and cyclin D1 were estimated. Histoapthological and immunohistochemical examinations were performed. RESULTS: Fisetin restored normal liver functions, increased reduced glutathione (GSH) level and decreased malondialdehyde (MDA), as well as inflammatory biomarkers including; tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, it lessened transforming growth factor ß1 (TGF-ß1), collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as elevated matrix metalloproteinase-9 (MMP-9) hepatic content. Furthermore, fisetin significantly suppressed wnt3a gene expression associated with decreased ß-catenin and increased GSK-3ß levels. Moreover, fisetin decreased the progress of histologic hepatic fibroplasia and diminished hepatic expression of α-SMA and cyclin D1. CONCLUSION: Fisetin curbed liver fibrosis and exhibited superior activity over silymarin through inhibition of hepatic stellate cells (HSCs) activation and proliferation via suppressing the Wnt/ß-catenin pathway, modulating MMP-9 and TIMP-1, and inhibiting multiple profibrogenic factors, besides its antioxidant and anti-inflammatory effects. Therefore, fisetin is a promising therapeutic candidate for hepatic fibrosis.

Nanoparticles of zinc oxide defeat chlorpyrifos-induced immunotoxic effects and histopathological alterations.

BACKGROUND AND AIM: Chlorpyrifos (CPF) is a widely used organophosphate insecticide. Nanoparticles of zinc oxide (ZnO NPs) physically showed effective adsorbing property for some insecticides. The study was conducted to estimate the potential effect of ZnO NPs against CPF toxicity. MATERIALS AND METHODS: Four groups of male rats were used; control group and three groups received drinking water contained 75 mg/L CPF, combined 75 mg/L CPF and 200 mg/L ZnO NPs, and 200 mg/L ZnO NPs, respectively. RESULTS: CPF significantly decreased macrophage activity, serum lysozyme activity, and levels of interleukin-2 (IL-2) and IL-6; increased the percentage of DNA degeneration on comet assay of lymphocytes and significantly elevated hepatic and splenic malondialdehyde contents; and decreased their glutathione contents. The liver and spleen showed marked histological alterations after exposure to CPF with decreased expression of acetylcholinesterase. The coadministration of ZnO NPs ameliorated most of the undesirable effects of CPF, through elevation of macrophage and serum lysozyme activities, increased the levels of IL-2 and IL-6, corrected the oxidative stress markers, and alleviated most of the adverse effect exerted by CPF in liver and spleen tissues. CONCLUSION: The addition of ZnO NPs to CPF-contaminated drinking water may be useful as a powerful antioxidant agent against toxic damage induced by CPF particularly in individuals who are on daily occupational exposure to low doses of CPF.

Neuropathology of aluminum toxicity in rats (glutamate and GABA impairment).

To get better insights into the pathological and biochemical defects underlying aluminum toxicity in brain tissue, we exposed male albino rats for 35 days to aluminum sulfate by gavage. Tissue aluminum level of brain was assessed, histological sections of brain were examined and amino acid transmitters contents were detected by reversed phase high performance liquid chromatography. Aluminum levels were high in brain specimens of the treated groups comparing to the control and it was dose-dependent. Marked increase in glutamate and glutamine levels was noticed while GABA level was significantly decreased. The most pronounced changes in brain tissue included spongioform changes in the neurons specially those of hippocampus, nuclear deformity, and neurofibrillary degeneration, similar to neurofibrillary tangles in Alzheimer's disease. It is concluded that accumulated aluminum in brain and altered amino acid neurotransmitters are important mechanisms of aluminum neurotoxicity.