New Protein Science May Protect Against Tylenol Induced Liver Damage

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Main Category: Liver Disease / Hepatitis
Article Date: 08 Sep 2011 - 9:00 PDT


In potentially tremendous news for liver damage patients, a new discovery has identified the protein Sab, or SH3-domain binding protein 5, as a key element in preventing liver damaged often caused by medications such as the very popular acetaminophen, otherwise your everyday Tylenol brand. Americans take over 8 billion pills (tablets or capsules) of Tylenol each year, while acetaminophen is the most common cause of drug induced liver disease and acute liver failure in the United States and United Kingdom.

Tylenol's maker announced in July that it was lowering the maximum recommended daily dosage to 3,000 milligrams to help prevent accidental overdoses. The OTC drug is a major ingredient in many cold and flu remedies as well as prescription painkillers like Percocet and Vicodin which are both highly prescribed.

For example, each tablespoon of the common nighttime cold remedy, NyQuil, contains 500 milligrams (mg) of acetaminophen. Similarly, each tablet of hydrocodone/acetaminophen (Vicodin), a popular, potent painkiller that contains a narcotic, has also either 500, 650, or 750 mg of acetaminophen, depending on the formulation.

Amounts of acetaminophen as low as 3 to 4 grams in a single dose or 4 to 6 grams over 24 hours have been reported to cause severe liver injury in some people, sometimes even resulting in death. Liver injury from acetaminophen occurs only when someone takes more than a certain amount of the drug. Likewise, the higher the dose, the greater is the likelihood of the damage.

Neil Kaplowitz, M.D., the study's lead investigator and professor of medicine at the Keck School at the University of Southern California said:

"Because the short-term activation of JNK is associated with cell survival, Sab is potentially a better target than inhibiting JNK, which could have adverse effects."

The research uncovered that the protein Sab in association with the enzyme JNK, regulates cellular metabolism and survival in response to stress, protecting cells when activated for brief intervals. Unfortunately, JNK also kills cells when activated for prolonged periods of time. In mice at least, Sab on the mitochondria of liver cells when silenced, protects against liver toxicity usually associated with excess doses of acetaminophen.

Kaplowitz continues:

"We proved that the sustained activation of JNK targets Sab and is a requirement for the subsequent death of liver cells. We then showed that it is a universal effect. Developing a drug to protect against cell death, one could argue to target JNK, but that's a double edged sword. This provides a whole new target: Create a drug that inhibits the interaction between JNK and Sab."

They also tested the effect on liver injury caused by apoptosis, or programmed cell death in response to inflammatory proteins that are implicated in many diseases and tissues. Silencing Sab protected the liver here as well.

Moreover, a person with liver disease does not appear to be at an increased risk of developing additional liver injury from taking Tylenol. This is so-regardless of the cause of the liver disease and provided the patient does not drink alcohol regularly.

Thus, Tylenol is quite safe to use in the recommended doses in patients with acute (brief duration) or chronic (long duration) hepatitis. For example, Tylenol is routinely prescribed to treat the flu-like symptoms that can be caused by interferon treatment for patients with chronic hepatitis. Keep in mind, however, that all drugs, including Tylenol, should be used with caution, if at all, in patients with severe liver disease, such as advanced cirrhosis (scarring of the liver) or liver failure.

Written by Sy Kraft
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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