Febuxostat ameliorates high salt intake-induced hypertension and renal damage in Dahl salt-sensitive rats

Miura, Tetsuji; Sakuyama, Akihiro; Xu, Li; Qiu, Jiahe; Namai-Takahashi, Asako; Ogawa, Yoshiko; Kohzuki, Masahiro; Ito, Osamu

doi:10.1097/hjh.0000000000003012

Cited by 6 publications

(4 citation statements)

References 50 publications

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“…However, inflammatory cell infiltration was detected in the kidneys of CIA mice on both NSD and HSD (Fig. 1n) [21].…”

Section: High-salt Diet Exacerbates Cia In Micementioning

confidence: 95%

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12

Zhang,

Zhao

et al. 2024

Int. J. Biol. Sci.

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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.

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“…However, inflammatory cell infiltration was detected in the kidneys of CIA mice on both NSD and HSD (Fig. 1n) [21].…”

Section: High-salt Diet Exacerbates Cia In Micementioning

confidence: 95%

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12

Zhang,

Zhao

et al. 2024

Int. J. Biol. Sci.

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“…Febuxostat attenuated proteinuria, renal dysfunction, and renal interstitial fibrosis but did not affect blood pressure in Nx-induced CRF rats [16]. Febuxostat attenuated hypertension, renal dysfunction, and renal histology in Dahl salt-sensitive rats fed a high-salt diet [17]. These results suggest that the ROS generation by NADPH oxidase and XO may induce blood pressure elevation and renal damages, respectively, and that superoxide dismutase may not affect blood pressure or renal damage in Nx-induced CRF rats.…”

Section: Introductionmentioning

confidence: 91%

Exercise Training Ameliorates Renal Oxidative Stress in Rats with Chronic Renal Failure

Yamakoshi

Nakamura

et al. 2022

Metabolites

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In patients with chronic kidney disease, exercise training with moderate intensity protects renal function and improves mortality. However, the mechanisms of the renal protective effects of exercise training in chronic kidney disease have not been clarified. This study investigated the effects of exercise training on renal NADPH oxidative and xanthine oxidase, which are major sources of reactive oxygen species, in rats with chronic renal failure. Six-week-old, male Sprague–Dawley rats were divided into the sham operation, 5/6 nephrectomy (Nx)+ sedentary, and Nx+ exercise training groups. The Nx+ exercise training group underwent treadmill running. After 12 weeks, systolic blood pressure, renal function, malondialdehyde, renal NADPH oxidase, and xanthine oxidase were examined. Nx induced hypertension, proteinuria, and renal dysfunction, and exercise training attenuated these disorders. Although the plasma levels of malondialdehyde were not different among the group, urinary levels were increased by Nx and decreased by exercise training. Renal activity and expression of NADPH oxidase and xanthine oxidase were increased by Nx and decreased by exercise training. These results indicate that exercise training attenuates hypertension and renal dysfunction and ameliorates NADPH oxidase and xanthine oxidase in rats with chronic renal failure, suggesting that the reduction of reactive oxygen species generation may be involved in the renal protective effects of exercise training.

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“…Febuxostat is considered a selective inhibitor of xanthine oxidoreductase (XOR), an enzyme that catalyzes the formation of uric acid. In Dahl salt-sensitive rats, orally administered febuxostat decreased the urinary excretion of TBARS, which was measured by means of a commercially available colorimetric batch TBARS assay [76]. XOR is also considered to generate superoxide anions, which in turn can mediate lipid peroxidation and increase MDA formation.…”

Section: Rarely Considered Issues Of Malondialdehyde-potential (Dual)...mentioning

confidence: 99%

Circulating and Urinary Concentrations of Malondialdehyde in Aging Humans in Health and Disease: Review and Discussion

Tsikas,

Mikuteit

et al. 2023

Biomedicines

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(1) Background: Malondialdehyde (MDA) is a major and stable product of oxidative stress. MDA circulates in the blood and is excreted in the urine in its free and conjugated forms, notably with L-lysine and L-serine. MDA is the most frequently measured biomarker of oxidative stress, namely lipid peroxidation. Oxidative stress is generally assumed to be associated with disease and to increase with age. Here, we review and discuss the literature concerning circulating and excretory MDA as a biomarker of lipid peroxidation in aging subjects with regard to health and disease, such as kidney disease, erectile dysfunction, and COVID-19. (2) Methods: Scientific articles, notably those reporting on circulating (plasma, serum) and urinary MDA, which concern health and disease, and which appeared in PubMed were considered; they formed the basis for evaluating the potential increase in oxidative stress, particularly lipid peroxidation, as humans age. (3) Results and Conclusions: The results reported in the literature thus far are contradictory. The articles considered in the present study are not supportive of the general view that oxidative stress increases with aging. Many functions of several organs, including the filtration efficiency of the kidneys, are physiologically reduced in men and women as they age. This effect is likely to result in the apparent “accumulation” of biomarkers of oxidative stress, concomitantly with the “accumulation” of biomarkers of an organ’s function, such as creatinine. How free and conjugated MDA forms are transported in various organs (including the brain) and how they are excreted in the urine via the kidney is not known, and investigating these questions should be the objective of forthcoming studies. The age- and gender-related increase in circulating creatinine might be a useful factor to be taken into consideration when investigating oxidative stress and aging.

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Febuxostat ameliorates high salt intake-induced hypertension and renal damage in Dahl salt-sensitive rats

Cited by 6 publications

References 50 publications

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12

Exercise Training Ameliorates Renal Oxidative Stress in Rats with Chronic Renal Failure

Circulating and Urinary Concentrations of Malondialdehyde in Aging Humans in Health and Disease: Review and Discussion

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