Acetaminophen Protects Kidneys After Muscle Injury
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.
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 in the Proceedings of the National Academy of Sciences that acetaminophen prevented oxidative damage and kidney failure after muscle injury in a rat model. The findings support further investigation of the drug's effects in patients with severe muscle injuries.
"This is a novel application of acetaminophen," said the study's lead author, Olivier Boutaud, Ph.D., research associate professor of Pharmacology. The idea "came from two groups working on different things and getting together to create something new," he said.
When skeletal muscle is damaged, it breaks down (lyses) - 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 deposits in the kidney and causes kidney failure by inducing oxidative damage to the kidney.
About the same time, Boutaud and John Oates, M.D., professor of Medicine and Pharmacology, were investigating the actions of acetaminophen. They discovered that acetaminophen blocked a "peroxidase" activity in an enzyme called cyclooxygenase.
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 said. "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. And importantly, the effective acetaminophen concentrations in the rat matched normal therapeutic concentrations in humans.
"Left to right: Olivier Boutaud, Ph.D., L. Jackson Roberts II, M.D., John Oates, M.D., have a paper in the journal PNAS showing that acetaminophen can prevent kidney damage caused by muscle injury in a rat model. (Credit: Photo by Joe Howell)"
Source: Vanderbilt University Medical Center
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