Study of correlation between lead-induced cytotoxicity and nitric oxide production in PC12 cells.

Toxicol Lett

Department of Pharmacology and Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, P.O. Box 14155-6183, Tehran, Iran.

Published: December 2005

AI Article Synopsis

  • Lead remains a significant health risk, primarily affecting the central nervous system due to its neurotoxic effects.
  • In a study using rat pheochromocytoma (PC12) cells, lead exposure was found to cause cytotoxicity and increase nitric oxide (NO) production in a dose-dependent manner.
  • Treatment with L-NAME, an inhibitor of nitric oxide synthase, showed that higher NO production significantly contributes to lead-induced toxicity, indicating a potential pathway for intervention.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.toxlet.2005.06.008DOI Listing

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