Phenolic alkaloid oleracein E attenuates oxidative stress and neurotoxicity in AlCl3-treated mice.

AIMS: Chelation therapy and antioxidant supplements have been demonstrated to be useful in ameliorating aluminum (Al) induced neurotoxicity. Oleracein E (OE) is a phenolic antioxidant alkaloid which possesses a rare tetrahydroisoquinoline/pyrrolidone tricyclic skeleton and a catechol moiety. The aim of this study was to investigate whether OE can chelate with Al and alleviate AlCl3-induced oxidative stress and neurotoxicity. MAIN METHODS: Kunming mice were administered AlCl3 (40mg/kg/d, i.p., 28days), with co-administration of OE (3mg/kg/d, 15mg/kg/d, i.g.) and the positive control piracetam (PA, 400mg/kg/d, i.g.). The Al contents in the brain and plasma were determined using ICP-MS. Al chelating ability of OE was assayed using UV spectroscopy. MDA, GSH, SOD or CAT, in the brain or plasma were determined. HE staining was used to examine hippocampal morphology alterations. IHC staining was employed to measure the expression of apoptotic-related proteins Bax, Bcl-2 and Caspase-3. KEY FINDINGS: AlCl3 remarkably increased the brain and plasma Al contents, increased lipid peroxidation and induced hippocampal neuronal damage. OE chelated with Al to form a stable complex. An increase in brain Al content by OE (15mg/kg) likely occurred through chelating with Al, which reduced the toxicity of free Al ion in the brain. OE significantly decreased MDA by regulating some antioxidant biomarkers. Furthermore, OE significantly ameliorated the protein expression changes in some apoptotic indices induced by AlCl3. SIGNIFICANCE: The phenolic alkaloid OE, as an antioxidant, Al chelator and apoptosis inhibitor, alleviates oxidative stress and neurotoxicity induced by AlCl3.

Neurotransmitters and neuronal apoptotic cell death of chronically aluminum intoxicated Nile catfish (Clarias gariepinus) in response to ascorbic acid supplementation.

Few studies have been carried out to assess the neurotoxic effect of aluminum (Al) on the aquatic creatures. This study aims to evaluate the neurotoxic effects of long term Al exposure on the Nile catfish (Clarias gariepinus) and the potential ameliorative influence of ascorbic acid (ASA) over a 180 days exposure period. Forty eight Nile catfish were divided into four groups: control group, placed in clean water, ASA exposed group (5mg/l), AlCl3 received group (28.96 µg/l; 1/20 LC50), and group received AlCl3 concomitantly with ASA. Brain tissue was examined by using flow cytometry to monitor the apoptotic cell population, HPLC analysis for the quantitative estimation of brain monoamine neurotransmitters [serotonin (5-HT), dopamine (DA), norepinephrine (NE)]. The amino acid neurotransmitters [serum taurine, glycine, aspartate and glutamine and brain gamma aminobutyric acid (GABA)] levels were assessed, plus changes in brain tissue structure using light microscopy. The concentration of Al in both brain tissue and serum was determined by using atomic absorption spectrophotometery. The Al content in serum and brain tissue were both elevated and Al exposure induced an increase in the number of apoptotic cells, a marked reduction of the monoamine and amino acids neurotransmitters levels and changes in tissue morphology. ASA supplementation partially abolished the effects of AL on the reduced neurotransmitter, the degree of apoptosis and restored the morphological changes to the brain. Overall, our results indicate that, ASA is a promising neuroprotective agent against for Al-induced neurotoxicity in the Nile catfish.