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Researchers funded by NIEHS developed a new model for predicting whether chemicals are toxic to the liver. The tool also identified a cellular pathway that might be involved in the process.

Because the liver plays a critical role in detoxification and metabolism, it is vulnerable to injury by environmental chemicals, commercial products, and drugs. In fact, liver toxicity is the leading cause of drug failure in clinical trials. However, traditional methods of testing for these effects are time-consuming and expensive.

To build their model, the team gathered data from reference drug lists on hundreds of chemicals known to cause liver toxicity and others with no known liver effects. They refined their tool by separating the chemicals into two groups: those that activate a specific cellular pathway in the liver that causes oxidative stress — a sign of injury — and those that do not. The team also incorporated information about chemical structural features that are involved in triggering oxidative stress.

The researchers validated the model by exposing human liver cells to 16 chemicals either implicated in oxidative stress or not, and then compared their experimental results with the model’s predictions for those compounds. Next, they entered five chemicals previously shown to cause liver toxicity and seven nontoxic chemicals into the model. Overall, the model successfully predicted the liver toxicity potential for most chemicals tested.

According to the team, this novel strategy can be used to develop additional models that consider other pathways involved in liver toxicity as well as models that predict toxicity in different organs.

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Source: Environmental Factor (August 2022)

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