Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats

Iron-tannic acid nanoparticles (Fe-TA NPs) presented MRI contrast enhancement in both liver cancer cells and preneoplastic rat livers, while also exhibiting an anti-proliferative effect via enhanced autophagic death of liver cancer cells. Hence, a toxicity assessment of Fe-TA NPs was carried out in...

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Main Authors: Chi Be Hlaing, Arpamas Chariyakornkul, Chalermchai Pilapong, Charatda Punvittayagul, Somdet Srichairatanakool, Rawiwan Wongpoomchai
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/12/7/1040
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author Chi Be Hlaing
Arpamas Chariyakornkul
Chalermchai Pilapong
Charatda Punvittayagul
Somdet Srichairatanakool
Rawiwan Wongpoomchai
author_facet Chi Be Hlaing
Arpamas Chariyakornkul
Chalermchai Pilapong
Charatda Punvittayagul
Somdet Srichairatanakool
Rawiwan Wongpoomchai
author_sort Chi Be Hlaing
collection DOAJ
description Iron-tannic acid nanoparticles (Fe-TA NPs) presented MRI contrast enhancement in both liver cancer cells and preneoplastic rat livers, while also exhibiting an anti-proliferative effect via enhanced autophagic death of liver cancer cells. Hence, a toxicity assessment of Fe-TA NPs was carried out in the present study. Acute and systemic toxicity of intraperitoneal Fe-TA NPs administration was investigated via a single dose of 55 mg/kg body weight (bw). Doses were then repeated 10 times within a range of 0.22 to 5.5 mg/kg bw every 3 days in rats. Furthermore, clastogenicity was assessed by rat liver micronucleus assay. Carcinogenicity was evaluated by medium-term carcinogenicity assay using glutathione <i>S</i>-transferase placental form positive foci as a preneoplastic marker, while three doses ranging from 0.55 to 17.5 mg/kg bw were administered 10 times weekly via intraperitoneum. Our study found that the LD<sub>50</sub> value of Fe-TA NPs was greater than 55 mg/kg bw. Repeated dose administration of Fe-TA NPs over a period of 28 days and 10 weeks revealed no obvious signs of systemic toxicity, clastogenicity, and hepatocarcinogenicity. Furthermore, Fe-TA NPs did not alter liver function or serum iron status, however, increased liver iron content at certain dose in rats. Notably, antioxidant response was observed when a dose of 17.5 mg/kg bw was given to rats. Accordingly, our study found no signs of toxicity, genotoxicity, and early phase hepatocarcinogenicity of Fe-TA NPs in rats.
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spelling doaj.art-d0e06f5feb1f47b486ae2690fd709c222023-11-30T23:43:30ZengMDPI AGNanomaterials2079-49912022-03-01127104010.3390/nano12071040Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in RatsChi Be Hlaing0Arpamas Chariyakornkul1Chalermchai Pilapong2Charatda Punvittayagul3Somdet Srichairatanakool4Rawiwan Wongpoomchai5Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Excellence for Molecular Imaging (CEMI), Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandResearch Affairs, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandIron-tannic acid nanoparticles (Fe-TA NPs) presented MRI contrast enhancement in both liver cancer cells and preneoplastic rat livers, while also exhibiting an anti-proliferative effect via enhanced autophagic death of liver cancer cells. Hence, a toxicity assessment of Fe-TA NPs was carried out in the present study. Acute and systemic toxicity of intraperitoneal Fe-TA NPs administration was investigated via a single dose of 55 mg/kg body weight (bw). Doses were then repeated 10 times within a range of 0.22 to 5.5 mg/kg bw every 3 days in rats. Furthermore, clastogenicity was assessed by rat liver micronucleus assay. Carcinogenicity was evaluated by medium-term carcinogenicity assay using glutathione <i>S</i>-transferase placental form positive foci as a preneoplastic marker, while three doses ranging from 0.55 to 17.5 mg/kg bw were administered 10 times weekly via intraperitoneum. Our study found that the LD<sub>50</sub> value of Fe-TA NPs was greater than 55 mg/kg bw. Repeated dose administration of Fe-TA NPs over a period of 28 days and 10 weeks revealed no obvious signs of systemic toxicity, clastogenicity, and hepatocarcinogenicity. Furthermore, Fe-TA NPs did not alter liver function or serum iron status, however, increased liver iron content at certain dose in rats. Notably, antioxidant response was observed when a dose of 17.5 mg/kg bw was given to rats. Accordingly, our study found no signs of toxicity, genotoxicity, and early phase hepatocarcinogenicity of Fe-TA NPs in rats.https://www.mdpi.com/2079-4991/12/7/1040acute toxicityrepeated dose toxicitycarcinogenicitygenotoxicitynanoparticle
spellingShingle Chi Be Hlaing
Arpamas Chariyakornkul
Chalermchai Pilapong
Charatda Punvittayagul
Somdet Srichairatanakool
Rawiwan Wongpoomchai
Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats
Nanomaterials
acute toxicity
repeated dose toxicity
carcinogenicity
genotoxicity
nanoparticle
title Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats
title_full Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats
title_fullStr Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats
title_full_unstemmed Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats
title_short Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats
title_sort assessment of systemic toxicity genotoxicity and early phase hepatocarcinogenicity of iron iii tannic acid nanoparticles in rats
topic acute toxicity
repeated dose toxicity
carcinogenicity
genotoxicity
nanoparticle
url https://www.mdpi.com/2079-4991/12/7/1040
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