In vitro and in vivo studies of a newly synthesized copper-cetyl tri-methyl ammonium bromide combined with gallium oxide nanoparticles complex as an antitumor agent against hepatocellular carcinoma.

Objective: Hepatocellular carcinoma (HCC) is one of the most leading causes of death worldwide. Previous studies reported that gallium alone and cetyltrimethylammonium bromide (CTAB) have antineoplastic activities; therefore, this study aimed to evaluate the activity of copper-cetyl tri-methyl ammonium bromide with gallium oxide nanoparticles (Cu-CTAB+GaO-NPs) against HCC by using in vitro and in vivo studies. Methods: In vitro study was performed to evaluate the cytotoxic effects of Cu-CTAB+GaO-NPs and GaO-NPs on HepG-2 cell line using crystal violet dye assay. In vivo study was done on diethyl nitrosamine (DEN) induced HCC Wister rats. Rats were randomly divided into eight groups; control, Cu-CTAB, GaO-NPs, Cu-CTAB+GaONPs, DEN, DEN+Cu-CTAB, DEN+GaO-NPs and DEN+Cu-CTAB+GaO-NPs. Histopathological examination of liver and biochemical parameters such as liver function markers, oxidative stress-antioxidants markers, tumor makers, apoptosis makers were studied. Results: Results obtained from in vitro study revealed that Cu-CTAB+GaO-NPs and GaO-NPs affect the cell viability of HepG-2 cancer cell with IC50 0.2 µg/ml and 360 µg/ml, respectively. Cu-CTAB+GaO-NPs exerted an antiproliferative effect in experimental rat models of HCC, as demonstrated both histologically, since it facilitated the tissue recovery of the damaged liver, and biochemically as showed by the reduction of liver function markers (ALT & AST), oxidative stress markers (MDA) and tumor makers (AFP,TGF-ß1,α-L-Fucosidase); while antioxidants markers (SOD), apoptosis markers (caspase-3 mRNA) and araginase activity were elevated in DEN+Cu-CTAB, DEN+GaO-NPs and DEN+Cu-CTAB+GaO-NPs groups when compared to DEN group. Conclusion: The present study demonstrated that both Cu-CTAB alone and/or combined with GaO-NPs exerted cytotoxic effects against DEN-induced HCC, which would in turn, speculate a possible therapeutic role of the novel Cu-CTAB+GaO-NPs compound.

Boswellic acid coated zinc nanoparticles attenuate NF-κB-mediated inflammation in DSS-induced ulcerative colitis in rats.

INTRODUCTION: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, and until now therapeutic agents for UC still cannot exert satisfied effects. Therefore, this study aimed to investigate the ameliorative effect of boswellic acid coated zinc nanoparticles (BAs-ZnNPs) on dextran sodium sulphate (DSS) induced-UC in rats. METHODS: Rats were divided into five groups; control, BAs-ZnNPs, DSS, DSS+BAs, and DSS + BAs-ZnNPs. The activity of alkaline phosphatase (ALP) was determined colorimetrically, while the concentration of IgM, IgG, TNF-α, IL-1ß, and IL-8 were measured by ELISA. Levels of gene expression of NF-κB and COX-2 genes were evaluated by RT-qPCR, while the expression of protein levels of PI3K and STAT-3 were done by western blotting. Finally, histopathological examination of colon tissues of different groups of rats was done. RESULTS: The depicted ball-like structure of the BAs-ZnNPs in the TEM images ranging in size from 50 to 100 nm in diameter while their formation was confirmed by UV-visible spectroscopy with a sharp peak of maximum absorbance at 266 nm. Our results revealed that BAs-ZnNPs exerted an anti-inflammatory effect in the experimental model of colitis, demonstrated histologically and biochemically as shown by the improvement of ALP, IgM, IgG, and the gene expression levels of NF-κB and COX-2. Also, this beneficial effect was associated with the reduction in the expression of TNF-α, IL-1ß, IL-8, PI3K, and STAT-3. Thus, this effect improves the altered immune response associated with the colonic inflammation. CONCLUSION: BAs-ZnNPs can be proposed as a therapeutic candidate to attenuate UC. The potential underlying mechanism includes suppression of ALP, IgM, IgG, IL-1ß, and IL-8 levels via regulation of NF-κB and COX-2 gene expression and STAT-3 and PI3K protein expression in a UC rat model.

Boswellic Acid Synergizes With Low-Level Ionizing Radiation to Modulate Bisphenol Induced-Lung Toxicity in Rats by Inhibiting JNK/ERK/c-Fos Pathway.

Bisphenol A (BPA) is a low molecular weight chemical compound that has a deleterious effect on the endocrine system. It was used in plastics manufacturing with injurious effects on different body systems. Occupational exposure to low-level ionizing radiation (<1 Gy) is shown to attenuate an established inflammatory process and therefore enhance cell protection. Therefore, the objective of this study was to investigate the protective effect of boswellic acid (BA) accompanied by whole-body low-dose gamma radiation (γ-R) against BPA-induced lung toxicity in male albino rats. BPA intoxication induced with 500 mg/kg BW. Rats received 50 mg BA/kg BW by gastric gavage concomitant with 0.5 Gy γ-R over 4 weeks. The immunoblotting and biochemical results revealed that BA and/or γ-R inhibited BPA-induced lung toxicity by reducing oxidative damage biomolecules; (MDA and NADPH oxidase gene expression), inflammatory indices (MPO, TNF-α, IL-6, and gene expression of CXCR-4). Moreover, BA and or/γ-R ameliorated the lung inflammation via regulation of the JNK/ERK/c-Fos and Nrf2/ HO-1 signaling pathways. Interestingly, our data demonstrated that BA in synergistic interaction with γ-R is efficacious control against BPA-induced lung injury via anti-oxidant mediated anti-inflammatory activities.