Compound from natural substance could one day prevent gout
HOUSTON, Texas — While gout is a common illness, there are only two available pharmaceutical treatments, and neither act as preventive methods. Thanks to a chemical compound created by researchers at Baylor College of Medicine, a safer, low toxicity prevention option was found to work in lab models and could one day be used in humans.
The findings appear in the journal Biochemical Pharmacology.
Overproduction or under excretion of uric acid can lead to Hyperuricemia (abnormally high levels of uric acid in the blood) and gout which is caused by crystallization and buildup of uric acid in joints and tissues. Its usual symptoms are red, swollen joints. The two treatments available are only effective after gout has developed and have been known to have harmful side effects in some cases.
“The only prevention method right now is diet and lifestyle. However, hyperuricemia and gout are associated with chronic diseases such as hypertension, diabetes, renal, and cardiovascular disease, so sometimes prevention can be complicated with other health issues,” said Dr. Changyi Chen, professor of surgery and chief of the division of surgical research at BCM. “A preventive treatment, with low toxicity, is needed. Our team of researchers has found a compound derived from natural substance that is very promising.”
Chen, who is also lead author in the study, and his colleagues, began by focusing on xanithine oxidase, or XO. It is a protein that plays an important role in the process that leads to gout. They focused on finding a chemical compound that would inhibit XO.
“We tested quite a few compounds, changed molecules around, and eventually tested 15 different compounds to find the right one,” said Chen.
The right one turned out to be derived from the natural substance protocatechuic aldehyde (a substance that can be obtained from certain plants), which proved to be a safer option than current treatments used for gout. In mouse models, those that received this compound presented no toxicity and neither did their offspring. When studied in the lab, and in dosages larger than what is prescribed, current treatments for gout had serious side effects such as hair loss and death that were not only present in the mouse models but also their offspring.
Another discovery the team noted was that the XO inhibitor also acted as an antioxidant. They found that their XO inhibitor reduced oxidative stress and endothelial dysfunction in human endothelial cells, which have been shown to play a role in cardiovascular disease.
“The results for our XO inhibitor compound are very exciting and can be very helpful in the move toward product development and clinical translation,” said Chen.