Acetaminophen Protects Kidneys?

(Ivanhoe Newswire) -- Severe muscle injuries, such as crush injuries suffered in earthquakes, car accidents and explosions, and muscle damage from excessive exercise or statin drug interactions can cause life-threatening kidney damage. Previously, treatment has been limited to intravenous fluids and dialysis, but a new study suggests that the commonly used pain reliever acetaminophen may protect the kidneys from damage.

An international research team led by investigators at Vanderbilt University Medical Center reports that acetaminophen prevented oxidative damage and kidney failure after muscle injury in a rat model.

"This is a novel application of acetaminophen,” lead author Olivier Boutaud, Ph.D., associate professor of pharmacology, was quoted as saying. The idea "came from two groups working on different things and getting together to create something new."

When skeletal muscle is damaged, it breaks down -- a condition called rhabdomyolysis -- and releases its cellular contents, including myoglobin, into the bloodstream. About 10 years ago, L. Jackson Roberts, II, M.D., and colleagues showed in a rat model that the released myoglobin was deposited in the kidney, causing kidney failure by inducing oxidative damage.

About the same time, Dr. Boutaud and John Oates, M.D., professor of medicine and pharmacology, were investigating the actions of acetaminophen. They discovered acetaminophen blocked a "peroxidase" activity in an enzyme. During informal conversations about their studies, members of the two teams realized that the myoglobin in the rat rhabdomyolysis model had a "pseudo-peroxidase" type of activity that was similar to the peroxidase activity blocked by acetaminophen.

"We said, 'aha, maybe acetaminophen would inhibit the pseudo-peroxidase activity of hemoproteins like myoglobin," Roberts was quoted as saying. "And it does."
Acetaminophen administered before or after the skeletal muscle injury in the rat model prevented oxidative injury to the kidneys, improved renal function and reduced renal damage. Importantly, the effective acetaminophen concentrations in the rat matched normal therapeutic concentrations in humans.

The investigators, in collaboration with Robert Mericle, M.D., in the Department of Neurological Surgery, are currently testing the effects of acetaminophen in patients with subarachnoid hemorrhage. In this condition, red blood cells in the cerebrospinal fluid break down and release hemoglobin, which has the same potential for causing oxidative damage, said Dr. Roberts.

Acetaminophen may prevent tissue damage in other conditions that involve blood cell breakdown, such as sickle cell disease and malaria, and in heart attacks, where cardiac muscle breakdown releases myoglobin into the circulation.

Roberts pointed out that soldiers at risk of suffering muscle injuries from gunfire or explosive devices may benefit from immediate administration of acetaminophen in the battlefield, as well.

SOURCE: Proceedings of the National Academy of Sciences, February 1, 2010

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