In:
Neuropathology and Applied Neurobiology, Wiley, Vol. 40, No. 6 ( 2014-10), p. 759-777
Abstract:
This study explores the neuroprotective effects and mechanisms of N ‐acetyl‐L‐cysteine ( NAC ) in mice exposed to cadmium ( C d). Methods NAC (150 mg/kg) was intraperitoneally administered to mice exposed to C d (10–50 mg/L) in drinking water for 6 weeks. The changes of cell damage and death, reactive oxygen species ( ROS ), antioxidant enzymes, as well as A kt/mammalian target of rapamycin (m TOR ) signalling pathway in brain neurones were assessed. To verify the role of m TOR activation in C d‐induced neurotoxicity, mice also received a subacute regimen of intraperitoneally administered C d (1 mg/kg) with/without rapamycin (7.5 mg/kg) for 11 days. Results Chronic exposure of mice to C d induced brain damage or neuronal cell death, due to ROS induction. Co‐administration of NAC significantly reduced C d levels in the plasma and brain of the animals. NAC prevented C d‐induced ROS and significantly attenuated C d‐induced brain damage or neuronal cell death. The protective effect of NAC was mediated, at least partially, by elevating the activities of C u/ Z n‐superoxide dismutase, catalase and glutathione peroxidase, as well as the level of glutathione in the brain. Furthermore, C d‐induced activation of A kt/m TOR pathway in the brain was also inhibited by NAC . R apamycin in vitro and in vivo protected against C d‐induced neurotoxicity. Conclusions NAC protects against C d‐induced neuronal apoptosis in mouse brain partially by inhibiting ROS ‐dependent activation of A kt/m TOR pathway. The findings highlight that NAC may be exploited for prevention and treatment of C d‐induced neurodegenerative diseases.
Type of Medium:
Online Resource
ISSN:
0305-1846
,
1365-2990
DOI:
10.1111/nan.2014.40.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
80371-6
detail.hit.zdb_id:
2008293-9
