Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney

2011 ◽  
Vol 300 (1) ◽  
pp. F189-F198 ◽  
Author(s):  
Sun-Young Hwang ◽  
Yaw L. Siow ◽  
Kathy K. W. Au-Yeung ◽  
James House ◽  
Karmin O
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Folic Acid ◽  
Nadph Oxidase ◽  
Superoxide Anion ◽  
Folic Acid Supplementation ◽  
Sod Activity ◽  
Superoxide Anion Production ◽  
Acid Supplementation ◽  
Anion Production

Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) levels, is a metabolic disease. It is a common clinical finding in patients with chronic kidney diseases and occurs almost uniformly in patients with end-stage renal disease. Hyperhomocysteinemia is also a risk factor for cardiovascular disease. Our recent studies indicate that hyperhomocysteinemia can lead to renal injury by inducing oxidative stress. Oxidative stress is one of the important mechanisms contributing to Hcy-induced tissue injury. Folic acid supplementation is regarded as a promising approach for prevention and treatment of cardiovascular disease associated with hyperhomocysteinemia due to its Hcy-lowering effect. However, its effect on the kidney is not clear. The aim of this study was to examine the effect of folic acid supplementation on Hcy-induced superoxide anion production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the kidney during hyperhomocysteinemia. Hyperhomocysteinemia was induced in male Sprague-Dawley rats fed a high-methionine diet for 12 wk with or without folic acid supplementation. A group of rats fed a regular diet was used as control. There was a significant increase in levels of superoxide anions and lipid peroxides in kidneys isolated from hyperhomocysteinemic rats. Activation of NADPH oxidase was responsible for hyperhomocysteinemia-induced oxidative stress in the kidney. Folic acid supplementation effectively antagonized hyperhomocysteinemia-induced oxidative stress via its Hcy-lowering and Hcy-independent effect. In vitro study also showed that 5-methyltetrahydrofolate, an active form of folate, effectively reduced Hcy-induced superoxide anion production via NADPH oxidase. Xanthine oxidase activity was increased and superoxide dismutase (SOD) activity was decreased in the kidney of hyperhomocysteinemic rats, which might also contribute to an elevation of superoxide anion level in the kidney. Folic acid supplementation attenuated xanthine oxidase activity and restored SOD activity in the kidney of hyperhomocysteinemic rats. These results suggest that folic acid supplementation may offer renal protective effect against oxidative stress.

Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophagesThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 369-378 ◽  
Author(s):  
Lindsei K. Sarna ◽  
Nan Wu ◽  
Sun-Young Hwang ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Cell Viability ◽  
Superoxide Anion ◽  
Pcr Analysis ◽  
Sod Activity ◽  
Superoxide Anion Production ◽  
Superoxide Anion Generation ◽  
Anion Production ◽  
Lps Treatment

Oxidative stress and amplified redox signaling contribute to the pathogenesis of many human diseases including atherosclerosis. The superoxide-generating phagocytic NADPH oxidase is a key source of oxidative stress in the developing atheroma. The aim of the present study was to examine the effect of berberine, a plant-derived alkaloid, on NADPH oxidase-mediated superoxide anion production in macrophages. Lipopolysaccharide (LPS) treatment activated NADPH oxidase in THP-1 monocyte-derived macrophages and increased the intracellular level of superoxide anions. Preincubation of cells with berberine demonstrated a concentration-dependent (10–50 µmol/L) and time-dependent (6–24 h) inhibition of superoxide anion generation in LPS-stimulated macrophages. Cell viability tests confirmed that berberine, at concentrations sufficient for inhibiting NADPH oxidase-mediated superoxide anion generation in macrophages, did not affect cell viability. Real-time PCR analysis revealed that addition of berberine to the culture medium was able to reduce gp91phox mRNA expression in LPS-treated cells. Berberine also restored superoxide dismutase (SOD) activity, which was found to be inhibited by LPS treatment. In conclusion, results from the present study demonstrate that berberine can effectively reduce intracellular superoxide levels in LPS- stimulated macrophages. Such a restoration of cellular redox by berberine is mediated by its selective inhibition of gp91phox expression and enhancement of SOD activity. The therapeutic relevance of berberine in the prevention and management of atherosclerosis remains to be further investigated.

Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophagesThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 141-147 ◽  
Author(s):  
Kathy K.W. Au-Yeung ◽  
Johnny C.W. Yip ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Folic Acid ◽  
Nadph Oxidase ◽  
Superoxide Anion ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Folic Acid Supplementation ◽  
Nuclear Factor ◽  
Superoxide Anion Production ◽  
Monocyte Chemoattractant Protein 1 ◽  
Acid Supplementation

Folic acid supplementation is a promising approach for patients with cardiovascular diseases associated with hyperhomocysteinemia. We have demonstrated that homocysteine (Hcy) activates nuclear factor-κB (NF-κB), a transcription factor that plays an important role in inflammatory responses. The aim of the present study was to investigate the effect of folic acid on Hcy-induced NF-κB activation in macrophages. Hcy treatment (100 μmol/L) resulted in NF-κB activation and increased monocyte chemoattractant protein-1 (MCP-1) expression in THP-1 derived macrophages. Hcy-induced NF-κB activation was associated with a significant increase in the intracellular superoxide anion levels. There was a significant increase in phosphorylation and membrane translocation of NADPH oxidase p47phox subunit in Hcy-treated cells. Addition of folic acid (200 ng/mL) to the culture medium abolished NADPH oxidase-dependent superoxide anion generation in macrophages by preventing phosphorylation of p47phox subunit. Consequently, Hcy-induced NF-κB activation and MCP-1 expression was inhibited. Such an inhibitory effect of folic acid was independent of its Hcy-lowering ability. Taken together, these results suggest that folic acid treatment can effectively inhibit Hcy-induced oxidative stress and inflammatory responses in macrophages. This may represent one of the mechanisms by which folic acid supplementation exerts a protective effect in cardiovascular disorders.

Folic acid supplementation attenuates high fat diet induced hepatic oxidative stress via regulation of NADPH oxidase

2012 ◽  
Vol 90 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Lindsei K. Sarna ◽  
Nan Wu ◽  
Pengqi Wang ◽  
Sun-Young Hwang ◽  
Yaw L. Siow ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Folic Acid ◽  
Liver Injury ◽  
Nadph Oxidase ◽  
High Fat Diet ◽  
Folic Acid Supplementation ◽  
High Fat ◽  
Acid Supplementation ◽  
Hepatic Oxidative Stress ◽  
Enhanced Expression

Diets high in saturated fat and cholesterol facilitate weight gain, a predisposing factor that contributes to the onset of obesity and metabolic disorders. Hepatic oxidative stress is commonly reported in various animal models of obesity and has been associated with enhanced expression of NADPH oxidase. We have previously reported several antioxidant mechanisms through which folic acid confers protection during hyperhomocysteinemia-induced oxidative stress. The objective of the present study was to investigate whether folic acid supplementation ameliorates high-fat diet induced oxidative stress in the liver, and to identify the underlying mechanisms. Male C57BL/6J mice were fed a control diet, a high-fat diet, or a high-fat diet supplemented with folic acid for 12 weeks. A high-fat diet led to increased body mass, hepatic lipid peroxidation, and liver injury. There was a significant increase in hepatic NADPH oxidase activity, which was associated with enhanced expression of several NADPH-oxidase subunits. Folic acid supplementation had a protective effect against high-fat diet induced hepatic oxidative stress and liver injury. Further analysis revealed that the antioxidant effect of folic acid was attributed, in part, to transcriptional regulation of NADPH oxidase. These results suggested that folic acid supplementation may be hepatoprotective from liver injury associated with a high-fat diet.

Impact of iron and folic acid supplementation on oxidative stress during pregnancy

2015 ◽  
Vol 35 (8) ◽  
pp. 803-806 ◽  
Author(s):  
E. Lymperaki ◽  
A. Tsikopoulos ◽  
K. Makedou ◽  
E. Paliogianni ◽  
L. Kiriazi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Folic Acid ◽  
Folic Acid Supplementation ◽  
Acid Supplementation ◽  
Iron And Folic Acid

Acute infusion of nicotine impairs nNOS-dependent reactivity of cerebral arterioles via an increase in oxidative stress

2007 ◽  
Vol 103 (6) ◽  
pp. 2062-2067 ◽  
Author(s):  
Denise M. Arrick ◽  
William G. Mayhan
Keyword(s):  
Oxidative Stress ◽  
Superoxide Anion ◽  
Potential Role ◽  
Acute Exposure ◽  
Cerebral Microcirculation ◽  
Superoxide Anion Production ◽  
Anion Production ◽  
Cerebral Arterioles ◽  
Oxide Synthase

Our goals were to determine whether acute exposure to nicotine alters neuronal nitric oxide synthase (nNOS)-dependent reactivity of cerebral arterioles and to identify a potential role for oxidative stress in nicotine-induced impairment in nNOS-dependent responses of cerebral arterioles. We measured in vivo diameter of cerebral arterioles to nNOS-dependent ( N-methyl-d-aspartate and kainate) and -independent (nitroglycerin) agonists before and during acute treatment with nicotine. We found that nNOS-dependent, but not -independent, vasodilatation was impaired during treatment with nicotine. In addition, treatment of the cerebral microcirculation with tempol (1 h before infusion of nicotine) prevented nicotine-induced impairment in nNOS-dependent vasodilatation. Furthermore, the production of superoxide anion (lucigenin chemiluminescence) was increased in parietal cortex tissue of rats by treatment with nicotine, and this increase in superoxide anion production could be inhibited by tempol. Our findings suggest that acute exposure to nicotine impairs nNOS-dependent dilatation of cerebral arterioles by a mechanism that appears to be related to the formation of superoxide anion.

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