Evaluation of in vivo cytogenetic toxicity of europium hydroxide nanorods (EHNs) in male and female Swiss albino mice

Abstract

Our group already demonstrated that europium hydroxide nanorods (EHNs) show none or mild toxicity in C57BL/6 mice even at high dose and exhibited excellent pro-angiogenic activity towards in vitro and in vivo models. In the present study, we evaluated the in vivo cytogenetic toxicity of intraperitoneally administered EHNs (12.5–250 mg/kg/b.w.) in male and female Swiss albino mice by analyzing chromosomal aberrations (CAs), mitotic index (MI), micronucleus (MN) from bone marrow and peripheral blood. Furthermore, we performed the cytogenetic toxicity study of EHNs towards Chinese hamster ovary (CHO) cells, in order to compare with the in vivo results. The results of CA assay of mice treated with EHNs (12.5–125 mg/kg/b.w.) showed no significant change in the formation of aberrant metaphases compared to the control group. Also, there was no significant difference in the number of dividing cells between the control group and EHNs-treated groups observed by MI study, suggesting the non-cytotoxicity of EHNs. Additionally, FACS study revealed that EHNs do not arrest cells at any phase of cell cycle in the mouse model. Furthermore, MN test of both bone marrow and peripheral blood showed no significant differences in the induction of MNs when compared with the control group. In vitro results from CHO cells also support our in vivo observations. Considering the role of angiogenesis by EHNs and the absence of its genotoxicity in mouse model, we strongly believe the future application of EHNs in treating various diseases, where angiogenesis plays an important role such as cardiovascular diseases, ischemic diseases and wound healing.

• CHO cells
• chromosomal aberrations assay
• genotoxicity
• inorganic nanorods
• micronucleus test
• mitotic index
• mouse model

Declaration of interest

The authors declare that they have no competing interest. The research was supported by “CSIR-Mayo Clinic Collaboration for Innovation and Translational Research” (CMPP 09; MLP0020; CKM) and 12th Five Year Plan (FYP) project (ADD: CSC0302). C.R.P. is grateful to DST, New Delhi, for Ramanujan Fellowship (SR/S2/RJN-04/2010; GAP0305). S.K.N. is thankful to DST, New Delhi, for supporting with INSPIRE fellowship. R.K.D. is thankful to CSIR, New Delhi for supporting with fellowship.

Supplementary material available online

Supplementary Figures S1-S7 and Tables S1-S6.