Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function

Fujikawa, Haruka; Sakamoto, Yuki; Masuda, Natsuki; Oniki, Kentaro; Kamei, Satoshi; Nakashima, Rumi; Maruta, Kasumi; Kawakami, Taisei; Eto, Yuka; Takahashi, N.; Tanaka, Takeo; Nakagata, Naomi; Watanabe, Hiroshi; Otake, Koji; Ogata, Yasuhiro; Tomioka, Nobuo; Hosoyamada, Makoto; Takada, Tappei; Ueno-Shuto, Keiko; Suico, Mary Ann; Kai, Hirofumi; Saruwatari, Junji; Shuto, Tsuyoshi

doi:10.3390/antiox9050387

Cited by 17 publications

(13 citation statements)

References 69 publications

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“…SUA may serve as a risk factor to predict poor thyroid function [ 25 ] or an indicator of malnutrition [ 15 ]. At a higher level, it activates inflammatory and oxidative mechanism action events in healthy subjects [ 26 ] and is a protective factor against the pathological decline of lung function [ 27 ] or an independent predictor for non-alcoholic fatty liver disease [ 28 ]. Abnormal SUA levels, either higher or lower, could increase the risk for mortality [ 29 , 30 ].…”

Section: Uric Acid and Goutmentioning

confidence: 99%

Why Does Hyperuricemia Not Necessarily Induce Gout?

Zhang

2021

Biomolecules

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Hyperuricemia is a risk factor for gout. It has been well observed that a large proportion of individuals with hyperuricemia have never had a gout flare(s), while some patients with gout can have a normuricemia. This raises a puzzle of the real role of serum uric acid (SUA) in the occurrence of gout flares. As the molecule of uric acid has its dual effects in vivo with antioxidant properties as well as being an inflammatory promoter, it has been placed in a delicate position in balancing metabolisms. Gout seems to be a multifactorial metabolic disease and its pathogenesis should not rely solely on hyperuricemia or monosodium urate (MSU) crystals. This critical review aims to unfold the mechanisms of the SUA role participating in gout development. It also discusses some key elements which are prerequisites for the formation of gout in association with the current therapeutic regime. The compilation should be helpful in precisely fighting for a cure of gout clinically and pharmaceutically.

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Section: Uric Acid and Goutmentioning

confidence: 99%

Why Does Hyperuricemia Not Necessarily Induce Gout?

Zhang

2021

Biomolecules

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“…A cross-sectional study reported improved FEV 1 in post-menopausal women with the SLC2A9 variant (rs11722228) variant associated with raised urate, suggesting a role for female hormones in urate antioxidant activity [32]. In contrast, a recent phenome-wide association study (PheWAS) in UK biobank indicated unspecified diseases of the respiratory system were potentially causally increased in older women with genetically raised urate [33].…”

Section: Comparison With Other Studiesmentioning

confidence: 99%

Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank

2021

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Background Serum urate is the most abundant small molecule with antioxidant properties found in blood and the epithelial lining fluid of the respiratory system. Moderately raised serum urate is associated with lower rates of lung cancer and COPD in smokers but whether these relationships reflect antioxidant properties or residual confounding is unknown. Methods We investigated the observational and potentially causal associations of serum urate with lung cancer incidence and FEV1 using one-sample Mendelian randomization (MR) and the UK Biobank resource. Incident lung cancer events were identified from national cancer registries as FEV1 was measured at baseline. Observational and genetically instrumented incidence rate ratios (IRRs) and risk differences per 10,000 person-years (PYs) by smoking status were estimated. Results The analysis included 359,192 participants and 1,924 lung cancer events. The associations between measured urate levels and lung cancer were broadly U-shaped but varied by sex at birth with the strongest associations in current smoking men. After adjustment for confounding variables, current smoking men with low serum urate (100 µmol/L) had the highest predicted lung cancer incidence at 125/10,000 PY (95%CI 56–170/10,000 PY) compared with 45/10,000 PY (95%CI 38–47/10,000 PY) for those with the median level (300 µmol/L). Raised measured urate was associated with a lower baseline FEV1. The MR results did not support a causal relationship between serum urate and lung cancer or FEV1. Conclusions We found no evidence that serum urate is a modifiable risk factor for respiratory health or lung cancer.

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“…Uric acid is an essential antioxidant in the body, and it is involved in the body's antioxidant system to resist various pathogenic factors [ 7 ]. However, uric acid exposure can increase oxidative stress in endothelial cells, proximal tubule epithelial cells, mesangial cells, adipocytes and other cells [ 8 ]. Oxidative stress is closely related to the activation of the NLRP3 inflammasome, which provides a new pathogenesis theory for the occurrence and development of hyperuricemia in chronic kidney disease.…”

Section: The Physiological Properties Of Uric Acidmentioning

confidence: 99%

Research progress on related mechanisms of uric acid activating NLRP3 inflammasome in chronic kidney disease

et al. 2022

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Hyperuricemia is an independent risk factor for the progression of chronic kidney disease. High levels of uric acid can lead to a series of pathological conditions, such as gout, urinary stones, inflammation, and uric acid nephropathy. There is a close relationship between uric acid and the NLRP3 inflammasome. NLRP3 inflammasome activation can cause cell damage and even death through endoplasmic reticulum stress, lysosome destruction, mitochondrial dysfunction, and the interaction between the Golgi apparatus and extracellular vesicles. In addition, the NLRP3 inflammasome acts as a molecular platform, triggering the activation of caspase-1 and the lysis of IL-1β, IL-18 and Gasdermin D (GSDMD) through different molecular mechanisms. Cleaved NT-GSDMD forms pores in the cell membrane and triggers pyrophosphorylation, thereby inducing cell death and releasing many intracellular proinflammatory molecules. In recent years, studies have found that hyperuricemia or uric acid crystals can activate NLRP3 inflammasomes, and the activation of NLRP3 inflammasomes plays an important role in kidney disease. This article reviews the possible pathophysiological mechanisms by which uric acid activates inflammasomes and induces kidney damage at the cellular and molecular levels.

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Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function

Cited by 17 publications

References 69 publications

Why Does Hyperuricemia Not Necessarily Induce Gout?

Why Does Hyperuricemia Not Necessarily Induce Gout?

Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank

Research progress on related mechanisms of uric acid activating NLRP3 inflammasome in chronic kidney disease

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