Assessment of chemical toxicity using mammalian mitochondrial electron transport particles

Abstract

New spectrophotometric bioassay procedures have been developed for evaluating chemical toxicity, using electron transport particles isolated from bovine heart mitochondria, based on the ability of many toxic chemicals to interfere with the integrated function of electron transport enzymes. The sensitivity of the mitochondrial assay is compared to published sensitivities of other in vivo and in vitro toxicity testing methods. Regression analysis of logarithmically transformed toxicity values for 42 chemicals, including 8 pesticides, 5 drugs, 6 metals, 8 alcohols, 5 respiratory inhibitors, 4 phenols, and 2 phthalates, indicates excellent correlation between the sensitivity of the new assays and the sensitivity of mammalian cytotoxicity studies (r2 = 0.86). Data from aquatic exposure toxicity tests conducted in fish are also highly correlated with the mitochondrial assay results (r2 = 0.79). However, correlation of data from these methods with median lethal dose studies conducted in rats is not as good because of the inability of in vitro and aquatic exposure analyses to account for the gastrointestinal absorption, hepatic metabolism, and excretion processes which modify toxic responses following oral administration.

Antioxidant capacity and toxicological evaluation ofPterospartum tridentatumflower extracts

“…Any interference with mitochondrial bioenergetics is known to be a part of cell injury process by a multiplicity of mechanisms and assorted agents (Wallace, 2008;Wallace, Eells, Madeira, Cortopassi, & Jones, 1997). Mitochondria has proven to be an excellent model to evaluate the many xenobiotics' effects on cell toxicity and the obtained data are usually in good agreement with cytotoxicity parameters reported in cell cultures and whole organisms (Haubenstricker, Holodnick, Mancy, & Brabec, 1990;Knobeloch, Blondin, Read, & Harkin, 1990). Based on these facts, the purpose of the present study was the assessment of potential toxicological effects of P. tridentatum flowers water extracts.…”

Investigating Drug-induced Mitochondrial Toxicity: A Biosensor to Increase Drug Safety?

“…Tests with submitochondrial particles were easier, faster and cheaper than whole animal test and culture analysis. By comparing mitochondrial data with serum drug concentrations, it was possible to partially validate the use of mitochondria as a bio-sensor to assess the human health risks related to the exposure to a chemical agent [211]. In addition, alterations of mitochondrial respiration could be another marker for mitochondrial toxicity.…”

“…The analytical protocols are easily performed and only require a spectrophotometer, pH meter and a household refrigerator [211]. Isolated mitochondria and further preparation of submitochondrial particles was also fairly easy, furthermore it was possible to freeze mitochondria or submitochondrial particles at different temperatures for a future use.…”

Selection of a battery of rapid toxicity sensors for drinking water evaluation

“…Mitoscan (Harvard Bioscience, Inc., Holliston, MA) measured enzyme activity of submitochondrial particles (SMPs), which are isolated vesicles of the inner membrane of bovine heart mitochondria containing membrane-bound enzymes associated with cellular electron transport and oxidative phosphorylation (Knobeloch et al, 1990). Two endpoints were monitored for each chemical tested: loss of nicotinamide adenine dinucleotide (NADH) using the electron transfer (ETR) protocol and production of NADH using the reverse electron transfer (RET) protocol.…”