title: Synthesis and dose interval dependent hepatotoxicity evaluation of intravenously administered polyethylene glycol-8000 coated ultra-small superparamagnetic iron oxide nanoparticle on Wistar rats.
abstract: Superparamagnetic iron oxide nanoparticles are being used in medical imaging, drug delivery, cancer therapy, and so on. However, there is a direct need to identify any nanotoxicity associated with these nanoparticles. However uncommon, drug-induced liver injury (DILI) is a major health concern that challenges pharmaceutical industry and drug regulatory agencies alike. In this study we have synthesized and evaluated the dose interval dependent hepatotoxicity of polyethylene glycol-8000 coated ultra-small superparamagnetic iron oxide nanoparticles (PUSPIOs). To assess the hepatotoxicity of intravenously injected PUSPIOs, alterations in basic clinical parameters, hematological parameters, hemolysis assay, serum levels of liver marker enzymes, serum and liver lipid peroxidation (LPO) levels, enzymatic antioxidant levels, and finally histology of liver, kidney, spleen, lung, brain, and heart tissues were studied in control and experimental Wistar rat groups over a 30-day period. The results of our study showed a significant increase in the aspartate transaminase (AST) enzyme activity at a dose of 10mg/kg b.w. PUSPIOs twice a week. Besides, alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) enzyme activity showed a slender increase when compared with control experimental groups. A significant increase in the serum and liver LPO levels at a dose of 10mg/kg b.w. PUSPIOs twice a week was also observed. Histological analyses of liver, kidney, spleen, lung, brain and heart tissue samples showed no obvious uncharacteristic changes. In conclusion, PUSPIOs were found to posses excellent biocompatibility and Wistar rats showed much better drug tolerance to the dose of 10mg/kg b.w. per week than the dose of 10mg/kg b.w. twice a week for the period of 30 days.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai- 600025, Tamil Nadu, India.
authors.forename: Balan
authors.initials: B
authors.lastname: Rajan
authors.affiliation: National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai- 600025, Tamil Nadu, India.
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Sathish
authors.affiliation: National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai- 600025, Tamil Nadu, India.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Balakumar
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai- 600025, Tamil Nadu, India. Electronic address: devakit@yahoo.co.uk.
authors.forename: Thiruvengadam
authors.initials: T
authors.lastname: Devaki
mesh_terms: D061605:Administration, Intravenous; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D052203:Ferrosoferric Oxide / Q000737:chemistry / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects; D060328:Magnetic Phenomena; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D011092:Polyethylene Glycols; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D052203:Ferrosoferric Oxide
keywords: Biocompatibility; Hemo-compatibility; Hepatotoxicity; Magnetic nanoparticles; Nanotoxicity; Polyethylene glycol