title: Cr (VI) induced oxidative stress and toxicity in cultured cerebellar granule neurons at different stages of development and protective effect of Rosmarinic acid.
abstract: Chromium (Cr) is a widespread metal ion in the workplace, industrial effluent, and water. The toxicity of chromium (VI) on various organs including the liver, kidneys, and lung were studied, but little is known about neurotoxicity. In this study, neurotoxic effects of Cr (VI) have been investigated by cultured cerebellar granule neurons (CGNs). Immature and mature neurons were exposed to different concentrations of potassium dichromate for 24 h and cytotoxicity was measured by MTT assay. In addition, immature neurons were exposed for 5 days as regards cytotoxic effect in development stages. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and the protective effect of Rosmarinic acid on mature and immature neurons exposed to potassium dichromate, were measured. Furthermore, lipid peroxidation, glutathione peroxidase (GPx), and acetylcholinesterase activity in mature neurons were assessed following exposure to potassium dichromate. The results indicate that toxicity of Cr (VI) dependent on maturation steps. Cr (VI) was less toxic for immature neurons. Also, Cr (VI) induced MMP reduction and ROS production in both immature and mature neurons. In Cr (VI) treated neurons, increased lipid peroxidation and GPx activity but not acetylcholinesterase activity was observed. Interestingly, Rosmarinic acid, as a natural antioxidant, could protect mature but not immature neurons against Cr (VI) induced toxicity. Our findings revealed vulnerability of mature neurons to Cr (VI) induced toxicity and oxidative stress.
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Dashti
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Soodi
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Amani
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D002857:Chromium / Q000633:toxicity*; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011192:Potassium Dichromate / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D000097123:Rosmarinic Acid
chemical_list: D000975:Antioxidants; D002857:Chromium; D002934:Cinnamates; D053630:Depsides; D018696:Neuroprotective Agents; D011192:Potassium Dichromate; D017382:Reactive Oxygen Species; D000097123:Rosmarinic Acid
keywords: Rosmarinic acid; chromium (VI); neurotoxicity; oxidative stress; primary neuron culture