Uric acid protects against lung function decline in females

Analyzing the role of uric acid in the lungs.

Past studies have suggested that high levels of uric acid could cause health problems such as gout and renal damage. But, a new study by the Kumamoto University in Japan has discovered that it protects against lung function decline in females.

Uric acid acts as an antioxidant that mitigates tissue-damaging oxidative stress–and is an essential factor for the living body. Found in lung tissue, but its function remains mostly obscure.

Hence, scientists decided to determine the role of uric acid in the lungs.

For their study, scientists created a murine lung disease model with high uric acid levels in the blood. Compared to humans, mouse uric acid levels are low, so the scientists used gene disruption and inhibitor treatments to suppress uricase (UOX), a murine urate-metabolizing enzyme, to increase uric acid levels.

They then created a lung disease mouse model with emphysema or chronic obstructive pulmonary disease (COPD) with elevated uric acid blood levels. They found that uric acid levels were high in female mice that had UOX gene disruption or UOX inhibitor treatments, and that their respiratory functions had improved.

On the other hand, when uric acid levels in male mice increased, symptoms of lung disease did not change or even worsened. This surprising finding suggests that uric acid protects the lungs of female mice.

Further experiments revealed that uric acid also suppresses oxidative stress in human lung epithelial cells. An analysis of female lung epithelial cells showed that the antioxidant effect of uric acid disappeared in the presence of female hormones.

Meanwhile, women with lower female hormone levels are more likely to benefit from the antioxidant effect of uric acid in lung tissue. This suggests that the protective effect of uric acid may be strongly exerted in elderly women who have decreased female hormone levels.

Epidemiological analyses targeting people 50 years or older revealed that uric acid levels and FEV1/FVC ratios (an indicator of respiratory function) were high among females with the SLC2A9/GLUT9 T/T genotype–a genotype known to have protective lung function qualities. 

Structural equation modeling further showed that this genotype is involved in lung function maintenance via elevated uric acid levels. Previous studies reported that female hormone therapy for menopausal women has a positive effect on maintaining lung function. 

It is therefore suggested that the antioxidative effect of uric acid is particularly significant for the protection of lung function in women whose hormones decrease with menopause.

Study leader Associate Professor Tsuyoshi Shuto said, “The results of this study strongly suggest that antioxidants such as uric acid are important for maintaining lung function in women with advanced age and advanced disease. We also previously reported that the antioxidant vitamin C and the antioxidant N-acetylcysteine slow the progression of lung disease.”

“In the future, we expect that the functions of uric acid and other antioxidants in the lungs will be reexamined, taking gender differences into account, so that they may be applied to improve health and treat lung diseases.”

Journal Reference:
  1. Fujikawa et al., Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function. DOI:10.3390/antiox9050387

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