Sex affects the response of Wistar rats to polyvinyl pyrrolidone (PVP)-coated silver nanoparticles in an oral 28 days repeated dose toxicity study
Abstract Background Silver nanoparticles (AgNPs) are widely used in biomedicine due to their strong antimicrobial, antifungal, and antiviral activities. Concerns about their possible negative impacts on human and environmental health directed many researchers towards the assessment of the safety and...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-10-01
|
| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12989-021-00425-y |
| _version_ | 1818836918868115456 |
|---|---|
| author | Marija Ćurlin Rinea Barbir Sanja Dabelić Marija Ljubojević Walter Goessler Vedran Micek Irena Žuntar Mirela Pavić Lucija Božičević Ivan Pavičić Ivana Vinković Vrček |
| author_facet | Marija Ćurlin Rinea Barbir Sanja Dabelić Marija Ljubojević Walter Goessler Vedran Micek Irena Žuntar Mirela Pavić Lucija Božičević Ivan Pavičić Ivana Vinković Vrček |
| author_sort | Marija Ćurlin |
| collection | DOAJ |
| description | Abstract Background Silver nanoparticles (AgNPs) are widely used in biomedicine due to their strong antimicrobial, antifungal, and antiviral activities. Concerns about their possible negative impacts on human and environmental health directed many researchers towards the assessment of the safety and toxicity of AgNPs in both in vitro and in vivo settings. A growing body of scientific information confirms that the biodistribution of AgNPs and their toxic effects vary depending on the particle size, coating, and dose as well as on the route of administration and duration of exposure. This study aimed to clarify the sex-related differences in the outcomes of oral 28 days repeated dose exposure to AgNPs. Methods Wistar rats of both sexes were gavaged daily using low doses (0.1 and 1 mg Ag/kg b.w.) of polyvinylpyrrolidone (PVP)-coated small-sized (10 nm) AgNPs. After exposure, blood and organs of all rats were analysed through biodistribution and accumulation of Ag, whereas the state of the liver and kidneys was evaluated by the levels of reactive oxygen species (ROS) and glutathione (GSH), catalase (CAT) activity, superoxide dismutase (SOD) and glutathione peroxidase (GPx), expression of metallothionein (Mt) genes and levels of Mt proteins. Results In all animals, changes in oxidative stress markers and blood parameters were observed indicating the toxicity of AgNPs applied orally even at low doses. Sex-related differences were noticed in all assessed parameters. While female rats eliminated AgNPs from the liver and kidneys more efficiently than males when treated with low doses, the opposite was observed for animals treated with higher doses of AgNPs. Female Wistar rats exposed to 1 mg PVP-coated AgNPs/kg b.w. accumulated two to three times more silver in the blood, liver, kidney and hearth than males, while the accumulation in most organs of digestive tract was more than ten times higher compared to males. Oxidative stress responses in the organs of males, except the liver of males treated with high doses, were less intense than in the organs of females. However, both Mt genes and Mt protein expression were significantly reduced after treatment in the liver and kidneys of males, while they remained unchanged in females. Conclusions Observed toxicity effects of AgNPs in Wistar rats revealed sex-related differences in response to an oral 28 days repeated exposure. |
| first_indexed | 2024-12-19T03:14:15Z |
| format | Article |
| id | doaj.art-40aa73aef240452fa76e0df1f196cd76 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-12-19T03:14:15Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-40aa73aef240452fa76e0df1f196cd762022-12-21T20:37:56ZengBMCParticle and Fibre Toxicology1743-89772021-10-0118111610.1186/s12989-021-00425-ySex affects the response of Wistar rats to polyvinyl pyrrolidone (PVP)-coated silver nanoparticles in an oral 28 days repeated dose toxicity studyMarija Ćurlin0Rinea Barbir1Sanja Dabelić2Marija Ljubojević3Walter Goessler4Vedran Micek5Irena Žuntar6Mirela Pavić7Lucija Božičević8Ivan Pavičić9Ivana Vinković Vrček10School of Medicine, University of ZagrebInstitute for Medical Research and Occupational HealthFaculty of Pharmacy and Biochemistry, University of ZagrebInstitute for Medical Research and Occupational HealthInstitute of Chemistry, University of GrazInstitute for Medical Research and Occupational HealthFaculty of Pharmacy and Biochemistry, University of ZagrebFaculty of Veterinary Medicine, University of ZagrebInstitute for Medical Research and Occupational HealthInstitute for Medical Research and Occupational HealthInstitute for Medical Research and Occupational HealthAbstract Background Silver nanoparticles (AgNPs) are widely used in biomedicine due to their strong antimicrobial, antifungal, and antiviral activities. Concerns about their possible negative impacts on human and environmental health directed many researchers towards the assessment of the safety and toxicity of AgNPs in both in vitro and in vivo settings. A growing body of scientific information confirms that the biodistribution of AgNPs and their toxic effects vary depending on the particle size, coating, and dose as well as on the route of administration and duration of exposure. This study aimed to clarify the sex-related differences in the outcomes of oral 28 days repeated dose exposure to AgNPs. Methods Wistar rats of both sexes were gavaged daily using low doses (0.1 and 1 mg Ag/kg b.w.) of polyvinylpyrrolidone (PVP)-coated small-sized (10 nm) AgNPs. After exposure, blood and organs of all rats were analysed through biodistribution and accumulation of Ag, whereas the state of the liver and kidneys was evaluated by the levels of reactive oxygen species (ROS) and glutathione (GSH), catalase (CAT) activity, superoxide dismutase (SOD) and glutathione peroxidase (GPx), expression of metallothionein (Mt) genes and levels of Mt proteins. Results In all animals, changes in oxidative stress markers and blood parameters were observed indicating the toxicity of AgNPs applied orally even at low doses. Sex-related differences were noticed in all assessed parameters. While female rats eliminated AgNPs from the liver and kidneys more efficiently than males when treated with low doses, the opposite was observed for animals treated with higher doses of AgNPs. Female Wistar rats exposed to 1 mg PVP-coated AgNPs/kg b.w. accumulated two to three times more silver in the blood, liver, kidney and hearth than males, while the accumulation in most organs of digestive tract was more than ten times higher compared to males. Oxidative stress responses in the organs of males, except the liver of males treated with high doses, were less intense than in the organs of females. However, both Mt genes and Mt protein expression were significantly reduced after treatment in the liver and kidneys of males, while they remained unchanged in females. Conclusions Observed toxicity effects of AgNPs in Wistar rats revealed sex-related differences in response to an oral 28 days repeated exposure.https://doi.org/10.1186/s12989-021-00425-yAccumulationToxicityOxidative stressMetallothioneinWistar rat |
| spellingShingle | Marija Ćurlin Rinea Barbir Sanja Dabelić Marija Ljubojević Walter Goessler Vedran Micek Irena Žuntar Mirela Pavić Lucija Božičević Ivan Pavičić Ivana Vinković Vrček Sex affects the response of Wistar rats to polyvinyl pyrrolidone (PVP)-coated silver nanoparticles in an oral 28 days repeated dose toxicity study Particle and Fibre Toxicology Accumulation Toxicity Oxidative stress Metallothionein Wistar rat |
| title | Sex affects the response of Wistar rats to polyvinyl pyrrolidone (PVP)-coated silver nanoparticles in an oral 28 days repeated dose toxicity study |
| title_full | Sex affects the response of Wistar rats to polyvinyl pyrrolidone (PVP)-coated silver nanoparticles in an oral 28 days repeated dose toxicity study |
| title_fullStr | Sex affects the response of Wistar rats to polyvinyl pyrrolidone (PVP)-coated silver nanoparticles in an oral 28 days repeated dose toxicity study |
| title_full_unstemmed | Sex affects the response of Wistar rats to polyvinyl pyrrolidone (PVP)-coated silver nanoparticles in an oral 28 days repeated dose toxicity study |
| title_short | Sex affects the response of Wistar rats to polyvinyl pyrrolidone (PVP)-coated silver nanoparticles in an oral 28 days repeated dose toxicity study |
| title_sort | sex affects the response of wistar rats to polyvinyl pyrrolidone pvp coated silver nanoparticles in an oral 28 days repeated dose toxicity study |
| topic | Accumulation Toxicity Oxidative stress Metallothionein Wistar rat |
| url | https://doi.org/10.1186/s12989-021-00425-y |
| work_keys_str_mv | AT marijacurlin sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT rineabarbir sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT sanjadabelic sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT marijaljubojevic sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT waltergoessler sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT vedranmicek sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT irenazuntar sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT mirelapavic sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT lucijabozicevic sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT ivanpavicic sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy AT ivanavinkovicvrcek sexaffectstheresponseofwistarratstopolyvinylpyrrolidonepvpcoatedsilvernanoparticlesinanoral28daysrepeateddosetoxicitystudy |