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.
I am fascinated by this topic because my dog had chronically high ALT and ALP values, indicating liver damage (confirmed by vet), and at a certain point, aged 11, he also began to show clinical signs of sickness: diarrhea, low urine output, abdominal discomfort, loss of appetite. His abdomen also began to show a lump, a probable tumor. After 3 short bouts of sickness over 3 months, from each of which he did recover, I put him on a very low-dose aspirin regime. He weighed c. 17 pounds, and I gave him 20 mg aspirin (ground up in food) every 48 hours. This is a tiny dose, rather like a human taking 81 mg per day. The dog immediately improved. For the next 2 months, no diarrhea, no low urine output, normal eating and drinking, and behaviour indicating much better pain control. Eventually, however, the abdominal tumors that had been identified some months ago began to grow large and fast, his walking continued to slow markedly, he had lost significant weight, and his ALT values had risen dramatically (13xULN). Cancer was suspected, and I agreed to have the dog euthanized. But I do believe that the tiny dose of aspirin I had him on gave him a very good quality of life during his last 2 months.