Total Antioxidant Status at High Altitude in Lowlanders and Native Highlanders: Role of Uric Acid

Sinha, Sudarson Sekhar; Singh, Som Nath; Ray, Uday Sankar

doi:10.1089/ham.2008.1082

Cited by 47 publications

(32 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…But, production of UA itself is associated with the generation of free radicals. Our previous study has shown that hypoxia-induced elevated UA does not play any beneficial role in maintaining antioxidant/prooxidant balance and acts as a camouflage to TAS (Sinha et al 2009). In the present study this hypothesis can again be supported by the significant increase in TAS level observed in all the groups after exercise.…”

Section: Discussionmentioning

confidence: 96%

Antioxidant and redox status after maximal aerobic exercise at high altitude in acclimatized lowlanders and native highlanders

et al. 2009

Self Cite

View full text Add to dashboard Cite

Exercise-induced increase in oxygen consumption leads to oxidative stress. On the contrary, hypoxia triggers oxidative stress despite decreased oxygen flux. Therefore, exercise under hypoxia may aggravate oxidative damage. Highlanders are expected to have better antioxidant capacity than lowlanders as a result of adaptation to hypoxia. The present study was undertaken to investigate the effect of exercise on antioxidant system in lowlanders and highlanders at high altitudes (HA). This study was conducted on active male volunteers, randomly selected and categorized into three groups, i.e., lowlanders tested at sea level (LL-SL, n = 35), lowlanders tested at altitude of 4560 m (LL-HA, n = 35) and native highlanders tested (HAN, n = 20) at the same height. Volunteers performed maximal exercise until exhaustion. Blood samples were collected before and after exercise. Both LL-SL and HAN had shown similar VO2max, which was significantly higher than LL-HA. GSH/GSSG ratio significantly increased in LL-SL and decreased in HAN after exercise. With exercise there were a decrease in superoxide dismutase and increase in glutathione peroxidase and catalase activities in HAN. Therefore, the results have suggested that HAN are more susceptible to oxidative stress when subjected to high-intensity exercise than lowlanders. The cumulative effect of higher VO2max and longer duration of exercise in hypoxia may be the reason of higher level of oxidative insult among HAN. Comparatively better management of antioxidant system observed in lowlanders at HA may be explained by the lower VO2max and shorter duration of exercise in hypoxia.

show abstract

Section: Discussionmentioning

confidence: 96%

Antioxidant and redox status after maximal aerobic exercise at high altitude in acclimatized lowlanders and native highlanders

et al. 2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, we are not the first to observe dissociation between urate and oxidative stress indices, protein carbonyl levels in particular. Clinical studies have revealed higher or unchanged protein carbonyls in patients with high urate, including refractory gout patients (30)(31)(32). Furthermore, urate has the capacity to act as a prooxidant under some circumstances (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Disrupted and transgenic urate oxidase alter urate and dopaminergic neurodegeneration

Chen

Burdett

Desjardins

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

112

121

View full text Add to dashboard Cite

Urate is the end product of purine metabolism in humans, owing to the evolutionary disruption of the gene encoding urate oxidase (UOx). Elevated urate can cause gout and urolithiasis and is associated with cardiovascular and other diseases. However, urate also possesses antioxidant and neuroprotective properties. Recent convergence of epidemiological and clinical data has identified urate as a predictor of both reduced risk and favorable progression of Parkinson's disease (PD). In rodents, functional UOx catalyzes urate oxidation to allantoin. We found that UOx KO mice with a constitutive mutation of the gene have increased concentrations of brain urate. By contrast, UOx transgenic (Tg) mice overexpressing the enzyme have reduced brain urate concentrations. Effects of the complementary UOx manipulations were assessed in a mouse intrastriatal 6-hydroxydopamine (6-OHDA) model of hemiparkinsonism. UOx KO mice exhibit attenuated toxic effects of 6-OHDA on nigral dopaminergic cell counts, striatal dopamine content, and rotational behavior. Conversely, Tg overexpression of UOx exacerbates these morphological, neurochemical, and functional lesions of the dopaminergic nigrostriatal pathway. Together our data support a neuroprotective role of endogenous urate in dopaminergic neurons and strengthen the rationale for developing urate-elevating strategies as potential disease-modifying therapy for PD.U rate, the anionic component of uric acid, predominates at physiological pH. As an apparent consequence of mutations in the urate oxidase (UOx) gene during primate evolution, urate constitutes the enzymatic end product of purine metabolism in humans (1). There remains controversy over how the loss of UOx activity and the resultant high urate concentrations in hominoids may have been beneficial and whether it still is. On one hand, urate is considered a pathogenic factor in gout, urolithiasis, and nephropathy, and hyperuricemia is associated with other medical conditions, such as hypertension, cardiovascular disease, and metabolic syndrome (2). On the other hand, the loss of UOx activity through multiple independent mutations in hominoids presumably conferred evolutionary advantages. Urate possesses potent antioxidant properties. High urate levels may have provided an antioxidant defense against aging and cancer, thereby contributing to a prolonged hominoid life span (3). In addition, increased urate may mediate blood pressure homeostasis in low-salt environments. Furthermore, higher urate has been suggested to enhance human intelligence or motivational behaviors or promote neuronal integrity and function (4).Recently a series of population and clinical epidemiology studies have lent support to a potential neuroprotective effect of urate (5,6). These studies demonstrated a robust inverse link between urate levels and both the risk and clinical progression of Parkinson's disease (PD), one of the most common neurodegenerative diseases. Given the putative role of oxidative stress in the pathogenesis of PD (7), these studies have i...

show abstract

“…Moreover, significantly raising serum urate concentration for 2 years was of no benefit in patients with relapsing-remitting multiple sclerosis (51). A positive correlation between plasma urate and PC levels has suggested that urate is ineffective in controlling oxidative stress in some other clinical settings (39,40). Although rare, inherited deficiencies of xanthine oxidase and the Urat1 transporter both cause lifelong hypouricemia, but neither has been associated with neurodegenerative diseases or other chronic illnesses linked to oxidative injury (52,53).…”

Section: Discussionmentioning

confidence: 99%

“…The level of carbonyl groups in plasma proteins has been used to assess oxidative stress in various disease states (24,(38)(39)(40). We used a standardized ELISA kit to measure PC levels in plasma obtained before treatment, and 1 wk after the first and fifth doses of pegloticase (Table 3).…”

Section: )mentioning

confidence: 99%

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo

Hershfield

Roberts²,

Ganson³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

124

View full text Add to dashboard Cite

A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associations. Pegloticase therapy generates H 2 O 2 while depleting urate, offering an in vivo test of the antioxidant hypothesis. We show that erythrocytes can efficiently eliminate H 2 O 2 derived from urate oxidation to prevent cell injury in vitro; during therapy, disulfide-linked peroxiredoxin 2 dimer did not accumulate in red blood cells, indicating that their peroxidase capacity was not exceeded. To assess oxidative stress, we monitored F2-Isoprostanes (F2-IsoPs) and protein carbonyls (PC), products of arachidonic acid and protein oxidation, in plasma of 26 refractory gout patients receiving up to five infusions of pegloticase at 3-wk intervals. At baseline, PUA was markedly elevated in all patients, and plasma F2-IsoP concentration was elevated in most. Pegloticase infusion rapidly lowered mean PUA to ≤1 mg/dL in all patients, and PUA remained low in 16 of 21 patients who completed treatment. F2-IsoP levels did not correlate with PUA and did not increase during 15 wk of sustained urate depletion. There also was no significant change in the levels of plasma PC. Because refractory gout is associated with high oxidative stress in spite of high PUA, and profoundly depleting uric acid did not increase lipid or protein oxidation, we conclude that urate is not a major factor controlling oxidative stress in vivo.

show abstract

Total Antioxidant Status at High Altitude in Lowlanders and Native Highlanders: Role of Uric Acid

Cited by 47 publications

References 40 publications

Antioxidant and redox status after maximal aerobic exercise at high altitude in acclimatized lowlanders and native highlanders

Antioxidant and redox status after maximal aerobic exercise at high altitude in acclimatized lowlanders and native highlanders

Disrupted and transgenic urate oxidase alter urate and dopaminergic neurodegeneration

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo

Contact Info

Product

Resources

About