Toxicological studies of newly developed nanomaterials of medical importance using in vivo and invitro model system.

Dr. Paramjit Grover Information Under Verification By PI.*

  • Project code : BT/PR/9998/NNT/28/84/2007
  • Designation :Scientist E-II
  • Department :Toxicology Unit - Biology Division
  • Affiliation :CSIR Indian Institute Of Chemical Technology, Hyderabad
  • Contact No. :91-40-27193135
  • Email Id :paramgrover@gmail.com
  • Sanctioned Amt :Rs. 92,12,064/-
  • Sanctioned Date :2007-11-01
  • Completion Date :2010-11-01
  • Web Url : http://www.incredb.org/investigator.php?incredb_id=284

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Summary of The Proposed Outcome.

NM have unique properties that are highly desirable for application within the medical sector. The innovation properties of NM have already found their first commercial and emerging biomedical applictions. If the NM of the current study are found to be toxicologically safe two new of medical importance will emerge for the benefit of mankind.

Outcomes.

Characterization of manganese oxide (MnO2) and chromium oxide (CrO3) nanomaterials (NMs) revealed that the size of NMs was MnO2-30 and CrO3-40. The in vitro parameters investigated were cytotoxicity using 3-[4,5-dimethylthiazol-2-yl]-2,5- mitrochondrial membrane potential (MMP), liposomal membrane potential (LMP), reactive oxygen species(ROS) and comet assay in human hepatocarcinoma (HepG2) cell line. Overall, the in vitro data suggested that MnO2 and CrO3 NP's were highly toxic whereas Fe2O3 NPs showed very low toxicity at the does tested. Acute oral toxicity of the compounds was greater than 2000mg/kg body weight. Repeated oral dose toxicity of studies (28 Day) of MnO2 and CrO3 in rats was also carried out using hematological parameters like hemoglobin, hematocrit, RBC, WBC, WBC differential count, clotting time in repeated doses of MNO2 and CrO3(nano and bulk materials) treated rats. Biochemical parameters like Acetylcholinesterase, different ATPases, Asparate aminotransferase, Alanine Aminotransferase and Lactate Dehydrogenase were monitored in repeated doses of MNO2 CrO3 treated rats. Genotoxicity assays like comet, chromosomal aberration and micronulceus test were analysed in acute and repeated doses of MNO2 and CrO3 treated rats. Antioxidant enzymes like gluyathione S-transferase, catalase, superoxide dismutase, glutathione peroxidase and gluthione reductase activities were assayed in repeated doses of MNO2 and CrO3 treated rats. Hisyopathological evaluation of various tissues from acute and repeated doses of MNO2 and CrO3 treated rats was also done. Toxicological effects were observed due to the repeated oral treated of MNO2-30, MnO2- Bulk, CrO3-40 and CrO3-Bulk materials. These alterations were mostly done and size dependent i.e. higher dosetreated animals showed more effect compare to lower done. Further, MnO2-30 was more as seen by ICPMS. High doses were used to provide detectable quantities once distributed through the animal and not intended to reflect likely human exposure. Our findings suggest that these NMs could be relatively safe when administered by oral route to the animal model for short periods of time. However, more studies are warranted for careful assessment to ensure safety of these NMs in biomedical applications.

Publication.

1    Monika Kumari, Sheik Rajak, Shailendra P. Singh, Upadhyayula S. N. Murty, Mohammed Mahboob, Paramjit Grover and Mohammed F. Rahman Biochemical alterations induced by acute oral doses of iron oxide nanoparticles in Wistar rats Drug and Chemical Toxicology 2013, 36, 296-305

2    Monika Kumari, Sheik Rajak, Shailendra Pratap singh, Srinivas indu kumari, Uday Kumar Putcha, Upadhyayula S. N. Murty, Mohammed Mahboob, Paramjit Grover and Mohammed F. Rahman Repeated Oral Dose Toxicity of Iron Oxide Nanoparticles: Biochemical and Histopathological Alterations in Different Tissues of Rats Journal of Nanoscience and Nanotechnology 2012, 12, 2149-2159

3    P. V. Prabhakar, Utkarsh A. Reddy, S. P. Singh, A. Balasubramanyam, M. F. Rahman, S. Indu Kumari, Sachin B. Agawane, U. S. N. Murty, Paramjit Grover and Mohammed Mahboob Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats Journal of Applied Toxicology 2012, 32, 436-445

4    Shailendra Pratap Singh, M. F. Rahman, U. S. N. Murty, M. Mahboob and Paramjit Grover Comparative study of genotoxicity and tissue distribution of nano and micron sized iron oxide in rats after acute oral treatment Toxicology and Applied Pharmacology 2013, 266, 56-66

5    Shailendra Pratap Singh, Monika Kumari, Srinivas I. Kumari, Mohammed F. Rahman, M. Mahboob and Paramjit Grover Toxicity assessment of manganese oxide micro and nanoparticles in Wistar rats after 28 days of repeated oral exposure Journal of Applied Toxicology 2013, 33, 1165 - 1179

6    Shailendra Pratap Singh, Monika Kumari, Srinivas I. Kumari, Mohammed F. Rahman, S. S. Kalyan Kamal, M. Mahboob and Paramjit Grover Genotoxicity of nano- and micron-sized manganese oxide in rats after acute oral treatment Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2013, 754, 39 - 50

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