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

SarnaLindsei, K; WuNan,; WangPengqi,; HwangSun-Young,; Siow, Yaw L.; OKarmin,

doi:10.1139/y11-124

Cited by 66 publications

(59 citation statements)

References 41 publications

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“…It has been found that leukocytes, potentially by producing pro-fibrotic mediators such as TGF-β1, affects HSCs and enhances ECM synthesis in various liver diseases [24]. Folic acid plays an important role as a potent antioxidant by scavenging free radicals and reducing oxidative stress, [25] to reduce the hepatic tissue damage in rats treated with carbon tetrachloride, [26] receiving a high-fat diet, [17] under chronic treatment with ethanol, [27] and receiving methotrexate [12]. Studies have shown that antioxidant supplements can significantly inhibit hepatic necrosis [28].…”

Section: Discussionmentioning

confidence: 99%

“…By limiting oxidative damage, folic acid reduces the severity of the inflammatory response and prevents fibrogenesis. Glutathione acts as a potent non-enzymatic antioxidant in the liver [17] and is a major component of the cellular defense mechanism against oxidative stress in BDL rats [22]. Several factors may have contributed to the reduced activity of GSH in BDL rats: (I) it may be inhibited by superoxide anions; (II) lipid hydrogen peroxides may inhibit glutathione peroxidase enzyme by binding to its GSH binding site; [22] (III) it can be affected by the flow of bile thiol or mediated by the induction of pro-inflammatory cytokine; (IV) reduced availability of amino acids required for GSH synthesis or defects in the trans-sulfuration pathway [29].…”

Section: Discussionmentioning

confidence: 99%

“…By eliminating free radicals and increasing acetaldehyde oxidation, folic acid prevents the inactivation of GSH [30]. Folic acid may act as a coenzyme for enzymes involved in the trans-sulfuration pathway and increases GSH synthesis and GSH levels [26] The lower GSH to GSSG ratio in BDL rats indicates oxidative stress [4,17]. Folic acid significantly improves this ratio by reducing the amount of oxidized glutathione and maintains the antioxidant defense in the liver [17].…”

Section: Discussionmentioning

confidence: 99%

“…Folic acid may act as a coenzyme for enzymes involved in the trans-sulfuration pathway and increases GSH synthesis and GSH levels [26] The lower GSH to GSSG ratio in BDL rats indicates oxidative stress [4,17]. Folic acid significantly improves this ratio by reducing the amount of oxidized glutathione and maintains the antioxidant defense in the liver [17]. The finding that folic acid, at the doses used in this study, significantly increases the GSH to GSSG ratio in healthy rats suggests that folic acid may have antioxidant effects.…”

Section: Discussionmentioning

confidence: 99%

“…After the incubation, the sample was added to a reaction mixture containing 0.2 mol/l sodium phosphate buffer (PBS), 0.2 mmol/l NADPH, 0.1 mmol/l DTNB, and 1.25 units of glutathione reductase. Following incubation for 10 minutes at room temperature, the absorbance of the mixture at 412 nm was measured [17].…”

Section: Assay Of Hepatic Reduced (Gsh) and Oxidized (Gssg) Glutathiomentioning

confidence: 99%

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Effects of folic acid on dyslipidemia and serum homocysteine in a rat model of cholestasis and hepatic fibrosis

Mohammadian¹,

Eidi²,

Mortazavi³

et al. 2015

pjp

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The liver is the major site for storage and metabolism of folate. Folate deficiency is common in many liver diseases and causes severe effects on cellular metabolism and increases oxidative stress and the homocysteine (Hcy) level. The objective of this research was to investigate the effects of folic acid on dyslipidemia and serum Hcy concentrations in an experimental rat model of cholestasis. Eighty-one male Wistar rats were divided into nine groups: control, sham-operated, folic acid control, bile duct-ligated (BDL), and BDL+ folic acid groups. In folic acid treated groups, folic acid (1, 5, and 10 mg/kg body weight) was given orally for 28 days. After taking blood and liver samples, plasma lipid profiles and Hcy and hepatic reduced and oxidized glutathione concentrations were measured. Histopathological features of cholestasis were assessed by Masson's trichrome staining. Treatment of folic acid in BDL rats significantly prevented the progression of hepatic fibrosis and improved the serum and liver biochemical changes. These results suggest that folic acid protects the liver against cholestasis by reducing serum Hcy and by its antioxidant properties. Folic acid can be an important therapeutic intervention in dyslipidemia caused by cholestasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Assay Of Hepatic Reduced (Gsh) and Oxidized (Gssg) Glutathiomentioning

confidence: 99%

See 3 more Smart Citations

Effects of folic acid on dyslipidemia and serum homocysteine in a rat model of cholestasis and hepatic fibrosis

Mohammadian¹,

Eidi²,

Mortazavi³

et al. 2015

pjp

View full text Add to dashboard Cite

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Folic Acid Supplementation Attenuates Chronic Hepatic Inflammation in High‐Fat Diet Fed Mice

Sid

Shang

Siow

et al. 2018

Lipids

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Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide. Hepatic inflammation is an important pathogenic mediator of NAFLD. There is currently no pharmacological agent approved for the treatment of NAFLD. Folic acid is a water‐soluble B vitamin that has been shown to have lipid‐lowering and antioxidant effects. The objective of this study was to investigate the effect of folic acid supplementation on hepatic inflammation and to identify the underlying mechanisms. Male C57BL/6 J mice were fed a control diet (10% kcal fat), a high‐fat diet (HFD) (60% kcal fat), or a HFD supplemented with folic acid (26 mg/kg diet) for 8 weeks. HFD feeding led to increased body mass gain, lipid accumulation, activation of transcription factor nuclear factor‐κB (NF‐κB), and elevation of inflammatory cytokine gene expression in the liver. Folic acid supplementation attenuated hepatic lipid accumulation and aggregation of inflammatory foci induced by HFD feeding. This was associated with a significant reduction of NF‐κB activation and inflammatory cytokine expression. These results suggest that the hepatoprotective effect of folic acid in NAFLD may be attributed, in part, to its anti‐inflammatory action.

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The Interactions Between Kynurenine, Folate, Methionine and Pteridine Pathways in Obesity

Engin¹

2017

Advances in Experimental Medicine and Biology

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Obesity activates both innate and adaptive immune responses in adipose tissue. Elevated levels of eosinophils with depression of monocyte and neutrophil indicate the deficiencies in the immune system of morbidly obese individuals. Actually, adipose tissue macrophages are functional antigen-presenting cells that promote the proliferation of interferon-gamma (IFN-gamma)-producing CD4+ T cells in adipose tissue of obese subjects. Eventually, diet-induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in visceral adipose tissue. Activity of inducible indoleamine 2,3-dioxygenase-1 (IDO-1) plays a major role under pro-inflammatory, IFN-gamma dominated settings. One of the two rate-limiting enzymes which can metabolize tryptophan to kynurenine is IDO-1. Tumor necrosis factor-alpha (TNF-alpha) correlates with IDO-1 in adipose compartments. Actually, IDO-1-mediated tryptophan catabolism due to chronic immune activation is the cause of reduced tryptophan plasma levels and be considered as the driving force for food intake in morbidly obese patients. Thus, decrease in plasma tryptophan levels and subsequent reduction in serotonin (5-HT) production provokes satiety dysregulation that leads to increased caloric uptake and obesity. However, after bariatric surgery, weight reduction does not lead to normalization of IDO-1 activity. Furthermore, there is a connection between arginine and tryptophan metabolic pathways in the generation of reactive nitrogen intermediates. Hence, abdominal obesity is associated with vascular endothelial dysfunction and reduced nitric oxide (NO) availability. IFN-gamma-induced activation of the inducible nitric oxide synthase (iNOS) and dissociation of endothelial adenosine monophosphate activated protein kinase (AMPK)- phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt)- endothelial NO synthase (eNOS) pathway enhances oxidative stress production secondary to high-fat diet. Thus, reduced endothelial NO availability correlates with the increase in plasma non-esterified fatty acids and triglycerides levels. Additionally, in obese patients, folate-deficiency leads to hyperhomocysteinemia. Folic acid confers protection against hyperhomocysteinemia-induced oxidative stress.

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

Cited by 66 publications

References 41 publications

Effects of folic acid on dyslipidemia and serum homocysteine in a rat model of cholestasis and hepatic fibrosis

Effects of folic acid on dyslipidemia and serum homocysteine in a rat model of cholestasis and hepatic fibrosis

Folic Acid Supplementation Attenuates Chronic Hepatic Inflammation in High‐Fat Diet Fed Mice

The Interactions Between Kynurenine, Folate, Methionine and Pteridine Pathways in Obesity

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