Research highlights clinical relevance of RNA/DNA urinary biomarkers of oxidative stress

A study performed by Marcus S. Cooke , professor in Florida International University’s Robert Stempel College of Public Health and Social Work’s Department of Environmental Health Sciences , along with visiting scholars Dr. Ying-Ming Shih, Chih-Hong Pan, Mu-Rong Chao and Ching-Wen Hu of Chung Shan Medical University in Taiwan, found that RNA and DNA damage provide better screening results, compared to lipid damage, as predictive biomarkers when testing for disease in urine.

Marcus CookeAdditionally, the researchers found that the temperature that is used to prepare urine samples can greatly affect study outcomes.

“This study further supports the potential utility of non-invasive biomarkers found in urine,” said Cooke. “These RNA or DNA biomarkers clearly have potential clinical utility that will aid in better understand the severity of an illness or how well a patient is responding to a treatment.”

The study, entitled Clinical relevance of guanine-derived urinary biomarkers of oxidative stress determined by LC-MS/MS was published in Redox Biology, volume 20 (2019), 556-565.

For the study, researchers developed a reliable and fast technique using liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three oxidized nucleic acid (RNA/DNA) damage products in urine. Then the researchers assessed the effect of various urine workup procedures on the urinary concentrations of the oxidized RNA/DNA products.

The results showed that frozen urine samples must be warmed (i.e., to 37 °C) to re-dissolve any precipitates prior to analysis, and that common workup procedures, such as thawing at room temperature or dilution with deionized water, are not capable of fully releasing the oxidized nucleic acid products from the precipitates, resulting in significant underestimation.

With this method, the researchers further assessed and compared the ability of the three oxidized RNA/DNA products, as well as a lipid biomarker (malodialdhyde, MDA), to biomonitor oxidative stress in vivo. MDA is commonly used as a biomarker of oxidative stress.Marcus Cooke

The researchers measured 315 urine samples from subjects with burdens of oxidative stress from low to high, including healthy subjects, patients with chronic obstructive pulmonary disease (COPD), and patients on mechanical ventilation (MV).

The results showed that both the COPD and MV patients had significantly higher urinary levels of the oxidized RNA/DNA products, but lower lipid levels, compared to healthy controls. The RNA/DNA products had a high ability to discriminate between urines from healthy individuals and patients. Surprisingly, this discrimination was low for MDA.

This study strongly supports the emerging evidence for a growing potential clinical utility for the measurement of oxidized RNA/DNA products.