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Protective Effect of Silver Nanoparticles Against Cytosine Arabinoside Genotoxicity: An In Vivo Micronucleus Assay
Idalia Yazmin Castañeda-Yslas1, Olivia Torres-Bugarín2, María Evarista Arellano-García3
1Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada 22860, Baja California, Mexico.
Abstract:
Cancer treatments have harmful side effects, including genotoxic ones. Our previous research discovered that a specific silver nanoparticle (AgNPs) formulation could reduce the genotoxic effects of an alkylating agent, cyclophosphamide. This study aims to evaluate if this protective effect is observed against an antimetabolite anticancer agent, cytosine arabinoside (Ara-C). An erythrocyte micronucleus assay was conducted on BALB/c mice. A most significant effect was observed after the application scheme, including three doses of Ara-C and three subsequent doses of AgNPs, resulting in a 3.7 and 2.0-fold decrease in the frequency of micronucleated reticulocytes and accumulated erythrocytes, respectively. Current and previous studies reveal that AgNPs could be used as a genoprotector against the genotoxic damage produced by the currently used antineoplastic antimetabolites and alkylating agents. It was revealed that AgNPs could be considered a new class of promising synthetic antineoplastic genoprotectants along with the known class of derivatives from natural sources.
Insights
Silver nanoparticles (AgNPs) protect against the genotoxic side effects of cancer drugs like cytosine arabinoside (Ara-C). This research shows AgNPs can act as synthetic genoprotectants, reducing chemotherapy-induced DNA damage.
Area of Science:
- Nanomedicine
- Toxicology
- Cancer Research
Background:
- Cancer chemotherapies, such as antimetabolites and alkylating agents, can cause harmful genotoxic side effects.
- Previous studies indicated that a specific silver nanoparticle (AgNPs) formulation demonstrated potential in mitigating genotoxicity induced by cyclophosphamide, an alkylating agent.
Purpose of the Study:
- To investigate the potential of the same silver nanoparticle (AgNPs) formulation to protect against the genotoxic effects of cytosine arabinoside (Ara-C), an antimetabolite anticancer agent.
- To evaluate AgNPs as a potential genoprotective agent against a different class of chemotherapy drugs.
Main Methods:
- The study utilized an erythrocyte micronucleus assay in BALB/c mice to assess genotoxicity.
- Mice were treated with cytosine arabinoside (Ara-C) followed by the specific silver nanoparticle (AgNPs) formulation.
Main Results:
- A significant protective effect was observed when AgNPs were administered after Ara-C treatment.
- The treatment scheme involving three doses of Ara-C and three subsequent doses of AgNPs led to a 3.7-fold decrease in micronucleated reticulocytes and a 2.0-fold decrease in accumulated erythrocytes.
- These findings suggest AgNPs can reduce chemotherapy-induced DNA damage.
Conclusions:
- Silver nanoparticles (AgNPs) show promise as genoprotective agents against the DNA damage caused by antimetabolite and alkylating anticancer drugs.
- AgNPs represent a potential new class of synthetic antineoplastic genoprotectants, complementing naturally derived compounds.

