Abstract
Mitomycin C (MMC) is an alkylating chemotherapy drug that could induce DNA damage and genetic alteration. It has been used as a model mutagen for in vivo and in vitro studies. The current study aimed to evaluate the protective role of Zinc oxide alginate–nanocomposites (ZnO-Alg/NCMs) against MMC–induced genotoxicity in mice. Animals were treated as follows: the control group, the groups treated with Algin (400 mg/kg b.w), the groups treated with ZnO-Alg/NCMs (400 mg/kg b.w), the group treated with MMC, and the groups treated with MMC plus Algin or ZnO-Alg/NCMs. Pre-treatment with Algin and ZnO-Alg/NCMs was repeated for one or seven days. Zinc oxide alginate-nanocomposites (ZnO-Alg/NCMs) were synthesized with the aim of incorporating the intrinsic properties of their constituents as an antigenotoxic substance. In this study, alginate was extracted from the brown marine alga Fucus vesiculosus, Zinc oxide nanoparticles were synthesized by using water extract of the same alga, and loaded in alginate to synthesize ZnO-Alg/NCMs. ZnO-NPs and ZnO-Alg/NCMs were characterized by TEM, SEM, EDX, and Zeta potential. The obtained results confirmed that by TEM and SEM, ZnO-NPs are rod shaped which modified, when loaded in alginate matrix, into spherical shape. The physical stability of ZnO-Alg/NCMs was reported to be higher than ZnO-NPs due to the presence of more negative charges on ZnO-Alg/NCMs. The EDX analysis indicated that the amount of zinc was higher in ZnO-NPs than ZnO-Alg/NCMs. The in vivo results showed that treatment with MMC induced genotoxic disturbances. The combined treatment with Algin and ZnO-Alg/NCMs succeeded in inducing significant protection against MMC. It could be concluded that ZnO-Algin/NCMs is a promising candidate to protect against MMC–induced genotoxicity.
Highlights
Exposure to various endogenous and environmental agents such as metals, pesticides, and alkylating agents, along with therapeutic compounds including antitumor and antibiotics [1], could induce DNA damage, genetic alteration, endothelial dysfunction, and tissue injury
Fourier-Transform Infrared Spectroscopy (FTIR) Analysis FTIR spectroscopy of the alginic acid and FTIR analysis of alginate extracted from brown alga F. vesiculosus were investigated, Figure 2 and Table 1
The current study revealed F. vesiculosus denoted more alginate yields than P. pavonica
Summary
Exposure to various endogenous and environmental agents such as metals, pesticides, and alkylating agents, along with therapeutic compounds including antitumor and antibiotics [1], could induce DNA damage, genetic alteration, endothelial dysfunction, and tissue injury. Mitomycin (MMC) is an alkylating DNA reactive antibiotic agent with anti-proliferative properties isolated from the Gram-positive actinobacteria Streptomyces caespitosus [2] It has been used in the treatment of gastric, bladder, pancreatic, and colon cancer [3]. Alginates are widely used technologically due to their physical characteristics, for example, their stabilizing, thickening, and emulsifying assets, and due to individual properties, such as gel strength, porosity, or biocompatibility. Their use is increasing in applications like biomaterials for tissue engineering and bio-printing [7]. Many recent studies investigated that various plant extracts can be used to manufacture metal oxide nanoparticles, including, remarkably, zinc oxide (ZnO-NPs). This study aimed to synthesize these by using biological algal extract and characterize the generated ZnO/Alg-NCMs by physical means, which subsequently will be investigated for its ability to reduce MMC induced genotoxicity
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