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Abstract Summary and conclusion The present work aimed to study antitumor efficiency of biologically synthesized gallium nanoparticles (GaNPs) by using Lactobacillus helveticus and/or low dose of gamma radiation against Ehrlich solid tumor model. Gallium nanoparticles were biologically synthesized by using Lactobacillus helveticus extracellular metabolites. Gallium nanoparticles were characterized by using transmission electron microscopy (TEM) analysis, Fourier transforms infrared spectroscopy (FTIR) and Ultraviolet-visible absorption (UV/VIS), and results revealed that; GaNPs were of size ranging 6–20 nm. The FTIR analysis of GaNPs showed shifting in wave number of functional groups due to their involvement in GaNPs capping and synthesis. UV/VIS scan showed absorption peak of GaNPs at 265 nm. In vitro study of GaNPs on tumor cell line MCF-7 showed toxicity with IC50 of 8.0 μg/ml. In vivo study, GaNPs LD50 was found to be 10 mg/kg b.w. Evaluation of GaNPs antitumor effect and/or gamma radiation in vivo was performed using eighty female swiss albino mice randomly divided into eight equal groups as follows: Summary and Conclusion 137 Group1 (Control): mice were intraperitoneal (i.p.) injected with (0.2) ml of sterile saline. Group2 (Ehrlich solid carcinoma (EC)): mice were injected intramuscularly in right thigh with 2x106 Ehrlich ascites carcinoma cells in sterile saline. group 3 (GaNPs): mice were i.p. injected with (1 mg/Kg b.w.) of prepared GaNPs daily. group 4 (Irradiation): mice whole body was exposed to a single dose of (0.25Gy) gamma irradiation. group 5 (GaNPs+Irradiation): Mice were i.p. injected with GaNPs daily as described in group 3 followed by gamma irradiation once as mentioned in group 4 . group 6 (EC+GaNPs ): Ehrlich solid carcinoma bearing mice as group 2 were i.p. injected with GaNPs daily starting at the 7th day of EAC inoculation as described in group 3. group 7 (EC +Irradiation): EC bearing mice as group 2 were once exposed to gamma irradiation as described in group 4. group 8 (EC+ GaNPs +Irradiation): EC bearing mice were injected i.p. with GaNPs daily as described in group 3 starting from 7th day followed by gamma irradiation as described in group 4 . Summary and Conclusion 138 After 21 days mice were sacrificed, blood was collected from the heart; liver and tumor tissues were dissected. The results revealed that solid Ehrlich solid tumor induced a significant increase in serum ALT activity, serum creatinine level, TLC count, liver MDA content, liver calcium and liver iron concentrations While GSH, CYP2E1 and Na+K+ATPase showed significant decrease compared to control group. EC bearing mice treated with GaNPs and/or γ-radiation exposure results a signficant reduction in the tumor volume, serum ALT activity, serum creatinine level, TLC in blood upon comparison with tumor group. While in the liver tissue showed, a significant increase in glutathione level, Na+K+ATPase activity, CYP450 (2E1) gene expression with a significant decrease in MDA concentration, the calcium and iron concentrations compared to EC group. Meanwhile in the tumor tissue results showed, a significant increase in MDA content, Na+K+ATPase, complexes II and III activity with a significant reduction in GSH level, calcium, iron concentrations and CYP450 (2E1) gene expression in mitochondria upon comparison with tumor bearing mice group. DNA fragmentation pattern of tumor tissue showed intense fragmentation accompanied with different treatments compared to EC group. Summary and Conclusion 139 Histopathological finding revealed that combined treatments of GaNPs with exposure to low dose of gamma radiation was more effective in damaging tumor cells compared to each treatment alone. Conclusion: from the aforementioned results, it is concluded that, GaNPs showed anti-carcinogenic activity to cancer cells. Combined treatment of GaNPs and low dose of radiation exposure showed great amelioration in tumor volume, TLC, liver and kidney functions lipid peroxidation, GSH, calcium and iron concentrations content besides mitochondrial parameters and histopathological findings. |