Melatonin Protection against Lead-Induced Changes in Human Neuroblastoma Cell Cultures

Abstract

The nervous system is the primary target for low-levels of lead (Pb) exposure and the developing brain appears to be especially vulnerable to Pb neurotoxicity. Chronic low-level Pb exposure causes growth retardation and intellectual impairment. In the present study the protective effect of melatonin during exposure to low-levels of Pb in human SH-SY5Y neuroblastoma cell cultures was assessed. The cells were exposed to Pb (0.01 to 10 microM) for 48 h. Pb inhibited the proliferation of neuroblastoma cells significantly in a concentration-dependent manner. A 50% inhibition (IC50) of cell proliferation was observed at about 5 microM Pb. Pb decreased (16% to 62%) the levels of total cellular glutathione (GSH) in a concentration (0.1 to 10 microM)-dependent manner. Exposure of cells to Pb (5 microM) for 48 h resulted in an eightfold increase in caspase-3 activity and prostaglandin E2 (PGE2) level. Pretreatment with melatonin (10 microM) blocked the effects of Pb on GSH content and caspase-3 activity, and showed significant improvement in reducing the level of PGE2. The results suggest that some of the neurotoxic effects of Pb may be partly mediated by apoptosis and pretreatment with melatonin can prevent these effects. The present study asserts the neuroprotective effect of melatonin in conditions of Pb-induced toxicity in neuroblastoma cell cultures.

Elucidation of mechanisms underlying the protective effects of olive leaf extract against lead-induced neurotoxicity in Wistar rats

“…Significant increase of proinflammatory mediators, such as TNF-α, IL-1β and PGE 2 was observed in the serum. Our data are in concordance with that of Suresh et al (2006) indicating that Pb induced PGE 2 in the hippocampus from Pbexposed rats. In culture system, Pb is able to modulate the expression of TNF-α in glial cells (Cheng et al, 2002).…”

Original Research: The expression of MMP2 and MMP9 in the hippocampus and cerebral cortex of newborn mice under maternal lead exposure

“…1 One of the heavy metals, lead has threatened environment sustainability and our future generations. Although research on lead neurotoxicity has been of interest for many years, [2][3][4][5][6][7] the effects of lead on the expression of MMP2 and MMP9 in the cerebral cortex and hippocampus still need to be elucidated.…”

“…Research has indicated that early life Pb exposure causes harm to brain development. 5,6 Both MMP2 and MMP9 play a vital role in the central nervous system. However, the potential effect of lead neurotoxicity remains unclear.…”

Overexpression of Ref-1 Inhibits Lead-induced Endothelial Cell Death via the Upregulation of Catalase

“…Based on our knowledge, it is well known that lead exposure increases the occurrence of cell death via apoptosis, such as neural (Suresh et al, 2006;Chetty et al, 2007), renal (Stacchiotti et al, 2009) and testicular cells (Adhikari et al, 2001;Massanyi et al, 2007). The cellular toxic effect of lead may be mediated by apoptosis.…”