In Vitro Assessment of Silver Nanoparticles Toxicity in Hepatic Mitochondrial Function
Abstract
This report results from a contract tasking IMAR-Mitochondrial Research Group as follows: The main toxicological concern is the fact that some of the manufactured nanomaterials are transported across cell membranes, especially into mitochondria. Nanoparticles-induced mitochondrial perturbation has important biologic effects, which include the initiation of apoptosis and decreased ATP production. Mitochondrial damage is a key event in particulate matter (PM) induced cytotoxicity. The initial response to PM is a decrease in mitochondrial membrane potential and increased O2 production, followed by cytochrome c release and inner mitochondrial membrane damage. A more recent study, showed that in BRL3A cells, nanoparticles lead to cellular morphological modifications, LDH leakage and mitochondrial dysfunction, in particular, cause increased generation of ROS, depletion of GSH, and reduction of mitochondrial membrane potential. Since mitochondria are provided with a variety of bioenergetic functions mandatory for the regulation of intracellular aerobic energy production and electrolyte homeostasis, impairment of mitochondrial function by nanoparticles may have drastic consequences on cellular function through the perturbation of the bioenergetic charge and balance of the cell. The mitochondrial inner membrane can undergo a permeability increase specifically inhibited by the immuno-supressive agent Cyclosporine A (Cy A). This transition is manifested by the transformation of a calcium-dependent, thiol-regulated, voltage-gated complex of membrane-spanning proteins, into a nonspecific pore capable of conducting solutes of <1500Da. Induction of the permeability transition pore (PTP) is widely implicated in the mechanism by which many agents interfere with mitochondrial bioenergetics in vitro.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 08, 2008
- Accession Number
- ADA491040
Entities
People
- Carlos M. Palmeira
Organizations
- University of Coimbra