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Antibacterial agent can weaken muscle

Triclosan impairs power of heart and other muscles

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10:14am, August 14, 2012
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A germ-fighting chemical added to many soaps, toothpastes and fabrics can interfere with how muscles contract, new research shows.

Doses of the chemical, called triclosan, needed to diminish muscle strength and blood flow in mice roughly matched those already measured in people in some parts of the United States, neurotoxicologist Isaac Pessah at the University of California Davis School of Veterinary Medicine and his colleagues report online August 13 in the Proceedings of the National Academy of Sciences. The report suggests that triclosan interferes with the movement of calcium into and out of cells.

“Calcium regulation is just so fundamental to the functioning of any organism,” observes Heiko Schoenfuss, a toxicologist and muscle physiologist at St. Cloud University in Minnesota who was not involved in the new study. “By demonstrating that calcium transport was affected,” he says, “this new study immediately opens up an entire Pandora’s box of possible other effects. This could be a major breakthrough.”

Although the agent was tested in mice and fish, the mechanism by which it impaired muscle activity also exists in people. U.S. surveys have found triclosan in fluid samples from about three-quarters of people tested.  So the new data “provide strong evidence that the chemical is of concern to both human and environmental health,” Pessah says.

Four years ago, Pessah’s team studied triclosan for its ability to disrupt various activities in mammalian cells. Triclosan appeared to have potent action in one unusual class of cellular gates — essentially biochemical locks that turn certain cellular activities on and off. Known as ryanodine receptors, these locks are part of the calcium channels that regulate the flow of calcium into and out of cells.

Calcium channels drive the activity of many cells, including those in muscle. Since the heart is muscle, Pessah decided to test whether triclosan might be capable of perturbing cardiac activity in exposed animals. He initially selected a dose that was less than 1 percent of what should have been lethal to animals. The first mouse tested died of heart failure within a minute of being dosed.

Stunned, the researchers dramatically ratcheted down the dose and were then able to show that in mice the chemical could reduce both the heart’s ability to move blood and the strength of leg muscles. The researchers then turned to fish, treating their water with somewhat higher doses of triclosan compared with the mouse experiments. Afterward, these fish couldn’t swim as fast as those living in untreated water.

Triclosan activates the calcium channel in muscle cells, Pessah says, but in an odd way that silences incoming nerve stimuli, diminishing the ability of muscles to contract.

Triclosan has become ubiquitous in municipal wastes and rivers owing to its use in a broad range of commercial products. Traces have even been detected in some tapwater samples. In another recent study, Schoenfuss and colleagues added triclosan to water containing fathead minnows — a species that serves as a lab rat of the aquatic world.

At low doses, triclosan impaired the swimming speed of young fish that were startled, the researchers reported in the July Archives of Environmental Contamination and Toxicology. In earlier work with other water contaminants, such as antidepressant drugs, this effect could be partially attributed to a dulling of the reaction time of the fish. But not here, Schoenfuss says.

Triclosan-exposed fish responded just as quickly as untreated ones, although the researchers couldn’t tease out why. “But part of what we saw matches very well what they suggest as a mode of action in the new paper,” he says.

Earlier work by Pessach’s group at UC Davis showed that certain other ubiquitous environmental contaminants, including certain polychlorinated biphenyls and a family of flame retardants known as polybrominated diphenyl ethers, also impair the operation of ryanodine receptors. The new work also suggests that the different chemicals’ have an additive effect on the receptors, Pessah says.

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