The devastating effect of exposure to high irradiation dose on liver and the performance of synthesized nano-Hap in relieve the associated symptoms in rats.

Ionizing radiation is one of the environmental factors that may contribute to liver dysfunction through a mechanism involving oxidative stress. This investigation studied the possible therapeutic effects of nano-HAp on hepatotoxicity in rats induced with gamma (γ) radiation. The study was carried out using 3 groups with 10 rats in each. Group 1 comprised the non-irradiated control rats, whereas the rats in groups 2 and 3 received a single dose of 10 Gy γ-radiation. The rats in group 3 were treated with nano-HAp [100 mg·(kg body mass)-1] once a week for 2 weeks starting the day after irradiation. The results showed that the rats exposed to γ-radiation had fragmented DNA, and significantly decreased levels of liver tissue enzymes such as paraoxonase 1, gamma glutamyl, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Pro-inflammatory factors such as interleukin (IL)-2, IL-6, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) in tissue were significantly increased compared with the controls. Also, exposure to γ-radiation significantly decreased the activity of superoxide dismutase and glutathione oxidase and increased lipid peroxidation in liver tissue. These effects were accompanied by severe histopathological changes to the hepatocytes. Intravenous injection of nano-HAp after irradiation has significant therapeutic potential against irradiation-induced liver damage because the treatment with nano-HAp restored antioxidant activity in the liver, antagonized the significant changes in the levels of IL-2, IL-6, TNF-α, IFN-γ, and restored the tissue level of paraoxonase 1, gamma glutamyl, ALT, and AST. Administering nano-HAp seemed to relieve the pathological changes induced by γ-radiation. Based on these results, it could be concluded that nano-HAp may have a therapeutic effect against liver dysfunction induced by γ-radiation through antagonizing the generation of free radicals and enhancing the antioxidant defense mechanisms.

Efficiency of calcium phosphate composite nanoparticles in targeting Ehrlich carcinoma cells transplanted in mice.

The present study aimed to investigate the mode of action of nano-CaPs in vivo as a therapy for solid tumor in mice. To achieve this goal, Ehrlich Ascites Carcinoma (EAC) was transplanted into 85 Swiss male albino mice. After nine days, the mice were divided into 9 groups. Groups 1 and 2 were allocated as the EAC control. Groups 3 and 4 were injected once intratumorally (IT) by nano-calcium phosphate (nano-CaP). Groups 5 and 6 received once intraperitoneal injection (IP) of nano-CaP. Groups 7, 8, and 9 received nano-CaP (IP) weekly. Blood samples and thigh skeletal muscle were collected after three weeks from groups 1, 3, 5, and 7 and after four weeks from groups 2, 4, 6, and 8. On the other hand, group 9 received nano-CaP (IP) for four weeks and lasted for three months to follow up the recurrence of tumor and to ensure the safety of muscle by histopathological analysis. Tumor growth was monitored twice a week throughout the experiment. DNA fragmentation of tumor cells was evaluated. In thigh tissue, noradrenaline, dopamine, serotonin (5HT), and gamma-aminobutyric acid (GABA) were measured. In serum, 8-Hydroxy-deoxyguanosine (8-OHDG), adenosine triphosphate (ATP), and vascular endothelial growth factor (VEGF) were analyzed. Histopathological and biochemical results showed a significant therapeutic effect of nano-CaP on implanted solid tumor and this effect was more pronounced in the animals treated IP for four weeks. This improvement was evident from the repair of fragmented DNA, the significant decrease of caspase-3, 8-OHDG, myosin, and VEGF, and the significant increase of neurotransmitters (NA, DA, 5HT, and GABA). Additionally, histopathological examination showed complete recovery of cancer cells in the thigh muscle after three months.