Study of correlation between lead-induced cytotoxicity and nitric oxide production in PC12 cells.
Despite reduction in its exposure, lead remains a major health problem. The primary target of lead toxicity is the central nervous system. The cellular, intracellular and molecular mechanisms of lead neurotoxicity are numerous, such as induction of apoptosis and interfering with Ca2+ dependent enzyme like nitric oxide synthase (NOS). To investigate the cytotoxic effect of lead on rat pheochromocytoma (PC12) cells, as a suitable model for neuroscience study, and possible correlation between lead toxicity and nitric oxide (NO) production, this study was performed. The current results showed that lead could induce cytotoxicity as well as NO production in a dose dependent manner in PC12 cells after 24h. The cytotoxicity was positively correlated with increased NOx (nitrite and nitrate) production in these cells. L-NAME, a NOS inhibitor, treatment (2.5 mM) could reverse this cytotoxicity. It can be concluded that lead-induced cytotoxicity in PC12 cells could partly be mediated by higher NO production.
Sharifi
Ali M
AM
Department of Pharmacology and Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, P.O. Box 14155-6183, Tehran, Iran. sharifal@yahoo.com
Mousavi
Seyed Hadi
SH
Bakhshayesh
Masoomeh
M
Tehrani
Fatemeh Khakinegad
FK
Mahmoudian
Masoud
M
Oryan
Shahrbanoo
S
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats
D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C008261:lead acetate; D019331:NG-Nitroarginine Methyl Ester