title: Genotoxicity of nano- and micron-sized manganese oxide in rats after acute oral treatment.
abstract: The use of nanotechnology has led to rapid growth in various areas. Manganese oxide (MnO2) nanomaterials (NMs) are typically used for biomedical applications. However, characterizing the potential human health effects of MnO2 NMs is required before fully exploiting these materials. The aim of this study was to investigate the acute oral toxicity of MnO2 NMs and MnO2-bulk particles in female albino Wistar rats. The genotoxic effects were examined using comet, micronucleus and chromosomal aberration assays. Nanosized MnO2 (45nm) significantly (p<0.01) increased DNA damage in peripheral blood leukocytes and micronuclei and enhanced chromosomal aberrations in the bone marrow cells at 1000mg/kg bw. These findings showed that the neurotoxicity of MnO2-45nm in the brain and red blood cells, as determined through acetylcholinesterase activity, was significantly (p<0.01) inhibited at 1000 and 500mg/kg bw doses. MnO2-45nm disrupted the physicochemical state and neurological system of the animals through alterations in ATPases via the total Na(+)-K(+), Mg(2+) and Ca(2+) levels in the brain P2 fraction. In addition, 500 and 1000mg/kg bw doses of MnO2-45nm caused significant changes in AST, ALT and LDH levels in the liver, kidney and serum of treated rats. Significant tissue distribution was found in all tissues in a dose- and time-dependent manner. MnO2-45nm exhibited much higher absorptivity and tissue distribution compared with MnO2-bulk. A large fraction of MnO2-45nm was cleared in the urine and feces. The histopathological analysis revealed that MnO2-45nm caused alterations in the liver, spleen and brain. These findings will provide fundamental information regarding the potential toxicities and biodistribution of nano and bulk MnO2 generated through acute oral treatment.
authors.affiliation: Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh 500 007, India.
authors.forename: Shailendra Pratap
authors.initials: SP
authors.lastname: Singh
authors.forename: Monika
authors.initials: M
authors.lastname: Kumari
authors.forename: Srinivas I
authors.initials: SI
authors.lastname: Kumari
authors.forename: Mohammed F
authors.initials: MF
authors.lastname: Rahman
authors.forename: S S Kalyan
authors.initials: SS
authors.lastname: Kamal
authors.forename: M
authors.initials: M
authors.lastname: Mahboob
authors.forename: Paramjit
authors.initials: P
authors.lastname: Grover
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002869:Chromosome Aberrations; D020552:Comet Assay; D005247:Feeding Behavior; D005260:Female; D017895:Manganese Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D015162:Micronucleus Tests; D046529:Microscopy, Electron, Transmission; D009929:Organ Size / Q000187:drug effects; D010087:Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D017895:Manganese Compounds; D010087:Oxides; C027424:manganese oxide