Lycopene protects against trimethyltin-induced neurotoxicity in primary cultured rat hippocampal neurons by inhibiting the mitochondrial apoptotic pathway.

Abstract

Lycopene is a potent free radicals scavenger with demonstrated protective efficacy in several experimental models of oxidative damage. Trimethyltin (TMT) is an organotin compound with neurotoxic effects on the hippocampus and other limbic structures and is used to model neurodegenerative diseases targeting these brain areas. Oxidative stress is widely accepted as a central pathogenic mechanism of TMT-mediated neurotoxicity. The present study investigated whether the plant carotene lycopene protects against TMT-induced neurotoxicity in primary cultured rat hippocampal neurons. Lycopene pretreatment improved cell viability in TMT-treated hippocampal neurons and inhibited neuronal apoptosis. Microfluorometric imaging revealed that lycopene inhibited the accumulation of mitochondria-derived reactive oxygen species (ROS) during TMT exposure. Moreover, lycopene ameliorated TMT-induced activation of the mitochondrial permeability transition pore (mPTP) and the concomitant depolarization of the mitochondrial membrane potential (ΔΨ(m)). Consequently, cytochrome c release from the mitochondria and ensuing caspase-3 activation were markedly reduced. These findings reveal that lycopene protects against TMT-induced neurotoxicity by inhibiting the mitochondrial apoptotic pathway. The anti-apoptotic effect of lycopene on hippocampal neurons highlights the therapeutic potential of plant-derived antioxidants against neurodegenerative diseases.

• Authors: Mingyue Qu, Zhou Zhou, Chunhai Chen, Min Li, Liping Pei, Fang Chu, Ju Yang, Yuan Wang, Li Li, Chuan Liu, Lei Zhang, Guangbin Zhang, Zhengping Yu, Denggao Wang
• Journal: Neurochemistry international (Neurochem Int) Vol. 59 Issue 8 Pg. 1095-103 (Dec 2011) ISSN: 1872-9754 [Electronic] England
• PMID: 22032970 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Neuroprotective Agents
• Reactive Oxygen Species
• Trimethyltin Compounds
• trimethyltin
• Carotenoids
• Cytochromes c
• Caspase 3
• Lycopene

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Carotenoids (pharmacology)
• Caspase 3 (metabolism)
• Cells, Cultured
• Cytochromes c (drug effects, metabolism)
• Hippocampus (cytology, drug effects, metabolism)
• Lycopene
• Membrane Potentials (drug effects, physiology)
• Mitochondria (drug effects, metabolism)
• Mitochondrial Membrane Transport Proteins (drug effects, physiology)
• Mitochondrial Permeability Transition Pore
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism, pharmacology)
• Trimethyltin Compounds (toxicity)