Nonalcoholic fatty liver disease (NAFLD) and hyperhomocysteinemia (HHcy) both are major health problems worldwide, whose incidence are closely related with each other. We previously reported the mechanism of HHcy-caused hepatic steatosis, but the role of n-3 polyunsaturated fatty acid (n-3 PUFA) in HHcy-induced hepatic steatosis remains unclear. In this study, 6-week-old C57BL/6 male mice were given a high methionine diet (HMD, 2% methionine diet), and plasma homocysteine levels were measured by ELISA to confirm the establishment of an HHcy model. Meantime, mice were fed HMD with or without n-3 PUFA supplement for 8 weeks to determine the role and mechanism of n-3 PUFA in hepatic steatosis induced by HHcy. Results showed that n-3 PUFA significantly improved hepatic lipid deposition induced by HHcy. qRT-PCR analysis demonstrated that n-3 PUFA inhibited the upregulation of Cd36, a key enzyme of fatty acid uptake, caused by HHcy. Further, the inhibition of hepatic Cd36 expression was associated with the inactivation of aryl hydrocarbon receptor (Ahr) induced by n-3 PUFA. Of note, mass spectrometry revealed that hepatic content of lipoxin A
Animals ; Fatty Acids, Omega-3 ; Fatty Liver/drug therapy* ; Hyperhomocysteinemia/drug therapy* ; Liver ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVETo explore the effect of low-dose folate on plasma homocysteinemia (Hcy) and chemokine levels in patients with hyperhomocysteinemia (HHcy).

METHODSForty HHcy patients were treated with 0.8 mg/d folate for 6 months. Plasma levels of Hcy, monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured before and after folate treatment.

RESULTSPlasma level of Hcy significantly decreased after folate treatment [(57.1 +/- 18.0) micromol/L vs (25.8 +/- 12.0) micromol/L, P <0.05]. However, the plasma levels of MCP-1, IL-8, SOD, and MDA were not changed after folate treatment.

CONCLUSIONFolate treatment can decrease the plasma Hcy level in HHcy patients; however, it has no obvious effects on the chemokine levels.

Aged ; Chemokines ; blood ; Female ; Folic Acid ; administration & dosage ; therapeutic use ; Homocysteine ; blood ; Humans ; Hyperhomocysteinemia ; blood ; drug therapy ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo study the effect of vitamin B on treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients.

METHODSThirty-six stable hyperhomocysteinemic renal-transplant recipients were randomly assigned to vitamin treatment (group A, n = 18, folic acid 5 mg/d, vitamin B(6) 50 mg/d, B(12) 1000 microg/d) or controlled group (group B, n = 18) for 6 months. All subjects underwent assessment of levels for creatinine, creatinine clearance, average pressure, total cholesterol, triglyceride and fasting homocysteine. Endothelial function was evaluated using high-resolution vascular ultrasound.

RESULTSThe levels of homocysteine markedly decreased in group A [(13 +/- 4) micromol/L vs (20 +/- 5) micromol/L, t = 5.3, P < 0.01] after treatment, whereas no significant changes were observed in group B. In group A, endothelium dependent [(12 +/- 5)% vs (9 +/- 5)%, t = 2.9, P < 0.01] and independent [(18 +/- 4)% vs (12 +/- 5)%, t = 3.4, P < 0.01] vasodilatation responses significantly increased after treatment, no significant changes were observed in group B. Endothelium dependent [(9 +/- 6)%, t = 2.8, P < 0.01] and independent [(12 +/- 5)%, t = 3.5, P < 0.01] vasodilatation responses of group A were significantly lower than that of group B after treatment.

CONCLUSIONSVitamin B supplementation can reduce the levels of homocysteine and improve the endothelial function in hyperhomocysteinemic renal-transplant recipients.

Adult ; Drug Therapy, Combination ; Endothelium, Vascular ; drug effects ; physiopathology ; Female ; Folic Acid ; administration & dosage ; Humans ; Hyperhomocysteinemia ; drug therapy ; physiopathology ; Kidney Transplantation ; Male ; Middle Aged ; Treatment Outcome ; Vitamin B 12 ; administration & dosage ; Vitamin B 6 ; administration & dosage

No abstract available.
Aged ; Anticoagulants/therapeutic use ; DNA Mutational Analysis ; Echocardiography ; Genetic Predisposition to Disease ; Homozygote ; Humans ; Hyperhomocysteinemia/blood/complications/diagnosis/drug therapy/*genetics ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; *Mutation ; Phenotype ; Pulmonary Embolism/blood/diagnosis/drug therapy/*etiology ; Severity of Illness Index ; Thrombolytic Therapy ; Tomography, X-Ray Computed ; Treatment Outcome ; Vitamins/therapeutic use

OBJECTIVETo explore targets of Chinese herbal medicine at cellular and molecular leve1s through an experimental study on Yinxingye Capsule (YC) intervening vascular endothelial cell apoptoeis of hyperhornocysteinemia (HHcy) rats.

METHODSThe HHcy model was prepared in male Wistar rats. Totally 42 rats were randomly divided into 4 groups, i.e., the control group (n =10), the model group (n = 11), the YC group (n =11), the folic acid group (n =10). Carboxy methyl cellulose (CMC) solution (1%) was administered to rats in the control group by gastrogavage.3% methionine suspension at 1. 5 g/kg was administered to rats in the model group by gastrogavage. 3% methionine suspension at 1. 5 g/kg and folic acid suspension at 0. 06 g/kg was administered to rats in the folic acid group by gastrogavage. 3% methionine suspension at 1. 5 g/kg and YC at 0. 02 g/kg was administered to rats in the YC group by gastrogavage. Morphological changes of aortic tissue were observed by hematoxylin eosin (HE) staining. The plasma homocysteine (Hcy) level was detected in each group. The endothelium-dependent diastolic functions of the thoracic aorta on different concentrations of sodium nitroprusside (SNP) and acetylcholine (Ach) were detected. Gene expressions of Bcl-2-associated X protein (BAX), inducible nitric oxide synthase (iNOS), c-Fos, cellular inhibitor of apoptosis protein 2 (c-IAP2) were detected by real time polymerase chain reaction (RT-PCR).

RESULTSPathological results showed that thickening aortic endothelium, swollen and desquamated endothelial cells. Few foam cells could be seen in the model group. Myoma-like proliferation of smooth muscle cells in tunica media could also be seen. These pathological changes were milder in the YC group and the folic acid group. Compared with the control group, plasma Hcy levels increased in the model group (P <0. 05). The endothelium-dependent diastolic rates at 10(-6) and 10(-4)mol/L Ach and 10(-7) -10(-3)mol/L SNP all decreased in the model group (P <0. 01, P <0. 05). Gene expressions of Bax, c-Fos, and iNOS increased, but c-IAP2 gene expressions decreased in the model group (all P <0. 05). Compared with the model group, plasma Hcy levels decreased in the YC group and the folic acid group (P <0. 05). The endothelium-dependent diastolic rates increased in the YC group and the folic acid group at various SNP concentrations except 10(-6) mol/L SNP in the folic acid group. The endothelium-dependent diastolic rates increased in the YC group and the folic acid group at 10(-6) and 10(-4)mol/L Ach (all P <0. 05). Gene expressions of Bax, c-Fos, and iNOS decreased in the YC group and the folic acid group, but c-IAP2 gene expression increased in the folic acid group (all P <0. 05).

CONCLUSIONYC could reduce plasma Hcy levels, down-regulate gene expressions of Bax, c-Fos, and iNOS, thereby reducing apoptosis of vascular endothelial cells, improving vascular endothelial function, and delaying atherosclerotic process.

Acetylcholine ; Animals ; Aorta ; Aorta, Thoracic ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelial Cells ; Endothelium, Vascular ; Hyperhomocysteinemia ; drug therapy ; Male ; Nitric Oxide Synthase Type II ; Nitroprusside ; Proto-Oncogene Proteins c-fos ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein