Pop an Aspirin, Protect Your Liver?

It is a common scenario for a student at Yale: you just got out of a mid-afternoon class, you have three midterms and a paper breathing down your neck, and you have a splitting headache to boot. Whether it is stress or an impending viral infection, students often reach to painkillers to relieve their symptoms. While many run to their first-aid kit and consume Advil, Tylenol, or Motrin without much thought, a recent Yale School of Medicine study demonstrates that not all painkillers are created equal.

In a study led by Dr. Wajahat Mehal, Associate Professor of Digestive Diseases and Immunobiol­ogy, new data suggests that aspirin may reduce liver toxicity induced by a variety of different agents in addition to serving as a general painkiller. This discovery has the potential to impact the phar­maceutical as well as the biotechnology industry.

In order to study the effects of aspirin on liver toxicity levels, Mehal introduced high levels of Tylenol into mice. Acetaminophen, the main ingredient in Tylenol, in high doses has been shown to induce severe liver damage. Therefore, it was not surprising that the mice treated with high doses of Tylenol sustained significant liver damage. However in a second set of tests, mice that were administered aspirin concurrently with the Tylenol “experienced some invulnerability to liver damage,” as compared to the control group. In this study, 80 percent of the mice in the “aspirin” group were shown to survive after induction of acetaminophen, whereas only 20 percent of the control group survived. This pro­vides a valuable clue indicating that aspirin may prevent liver damage that would have otherwise been unavoidable.

In explaining the mechanism by which aspirin can protect the liver, Mehal uses principles from immunobiology. Typically, a body’s defensive white blood cells respond to an inflammatory challenge from a pathogen. The main pathway that the response takes is the production of cytokines, reg­ulatory proteins that can induce and intensify the inflammatory response. This effectively destroys the pathogen, but the heightened response can also be harmful to the body and occasionally induce auto-inflammatory damage. Mehal states, “Aspirin may work to decrease the production of cytokines, thereby reducing the damage induced by the inflammatory response.”

Many pain relieving medications work by a numbing mechanism. They decrease the trans­mission of painful neural signals to the brain and dull the feelings of pain. According to Mehal, aspirin functions by striking the pain at its source; it decreases the inflammatory response that is causing the pain in the first place. However, aspi­rin has other characteristics that prevent its use as a widespread replacement for other medica­tions. “When taken in the recommended doses, Tylenol and other medications are absolutely safe, whereas aspirin can cause stomach pain and other side effects in many people,” said Mehal.

Mehal’s finding has wide implications. Medi­cines that were formerly deemed unusable because they caused high levels of liver damage could re-enter testing, this time accompanied by aspirin. Statins, used by millions of Americans every day to keep cholesterol levels in control, could be more effective and less toxic if admin­istered with a dose of aspirin.

Mehal notes that the broad mechanism by which aspirin works to prevent liver damage lends its application to a wide variety of situations, “By reducing overall inflammation in the liver, we can reduce overall injury.” This means that aspirin may also be used in the future to protect from other sources of liver damage, including alcohol consumption and other drugs.

However, there are caveats. As of yet, there is no proposed mechanism by which aspirin might reduce previously inflicted liver damage. Addi­tionally, clinical trials must be conducted before any conclusive evidence about the benefits of aspirins in humans can be obtained. Nonetheless, Mehal’s findings are fascinating to the medical community and pharmaceutical industry, likely to have wide implications in future research and patient treatment.