Investigating the protective effect of glutamine against cerebral ischemia and bilateral carotid occlusion in rats.

Background: This study aims to investigate the protective effects of glutamine against cerebral injury resulting from cerebral ischemia-reperfusion by bilateral carotid occlusion in rats. Methods: Eighteen Wistar albino rats were randomly divided into three equal groups: 1) control group; 2) ischemia-reperfusion group which underwent clamping of the carotid artery for 20 min; and 3) ischemiareperfusion + glutamine group which was treated with two doses of glutamine (1 g/kg) prior to the same clamping procedure as the ischemia-reperfusion group. All rats were sacrificed 24 h after the experiment. Their brain tissue was removed, separated into right and left hemispheres, and sent for analysis. Biochemical analysis was used to determine the oxidant parameters, antioxidant parameters, and glutathione levels in brain tissue. In the histopathological analysis of the brain tissue, ischemic markers such as red neurons, spongiosis, and satellitosis were examined. Results: Biochemical examination revealed that the levels of malondialdehyde and ferric reducing antioxidant power in the ischemia-reperfusion group were significantly higher than those in the control and ischemia-reperfusion + glutamine groups (p<0.05). The histopathological findings revealed that the levels of red neurons, satellitosis, and spongiosis in the ischemia-reperfusion group were significantly higher than those in the control group (p<0.05). The red neuron and spongiosis levels in the ischemia-reperfusion + glutamine group were significantly higher than those in the control group (p<0.05). Conclusion: Our study findings indicate that glutamine treatment has a protective effect against ischemia-reperfusion-induced brain damage in rats.

The effect of 1,25-dihydroxyvitamin D3 on liver damage, oxidative stress, and advanced glycation end products in experimental nonalcoholic- and alcoholic- fatty liver disease

Background/aim: Oxidative stress and advanced glycation end products (AGEs) formation are proposed as effective mechanisms in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). 1,25(OH)2D3 was proposed to have antioxidant, antiinflammatory and antiglycation properties. In this study, the effect of 1,25(OH)2D3 treatment on oxidative stress parameters and AGEs levels together with hepatic histopathology was investigated in high fructose (HFr) or ethanol (EtOH)-treated rats. Materials and methods: Rats were treated with fructose (30%) or ethanol (5-20%) in drinking water with and without 1,25(OH)2D3 treatment (5 µg/kg two times a week) for 8 weeks. Insulin resistance (IR), oxidative stress parameters, AGEs, triglyceride (TG), and hydroxyproline (Hyp) levels together with histopathology were investigated in the liver. Results: 1,25(OH)2D3 decreased hepatic reactive oxygen species, lipid and protein oxidation products together with histopathological improvements in HFr- and EtOH-treated rats. 1,25(OH)2D3 treatment was observed to decrease significantly serum and hepatic AGEs in HFr group, and hepatic AGEs in EtOH group. Conclusion: Our results clearly show that 1,25(OH)2 D3 treatment may be useful in the alleviation of hepatic lesions by decreasing glycooxidant stress in both NAFLD and ALD models created by HFr- and EtOH-treated rats, respectively.

A preliminary study about neurofilament light chain and tau protein levels in psoriasis: Correlation with disease severity.

BACKGROUND: Studies investigating cognitive dysfunction in psoriatic patients remain inconclusive. OBJECTIVE: To investigate the risk of cognitive decline in plaque-type psoriasis patients. METHODS: Serum neurofilament light chain (NFL) and tau protein concentrations in 45 patients with plaque-type psoriasis and forty-five healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean homeostasis model assessment (HOMA-IR) values (6.82 vs 3.25) and serum levels of insulin (28.19 vs 15.71), NFL (5.74 vs 1.98), and tau (348.17 vs 207.30) in patients with psoriasis were found to be significantly higher than those of in healthy controls. There was a significant positive correlation between NFL and tau (r = .257, P = .015). There was significant correlation between NFL, tau and PASI (r = .310, P = .040) and (r = .383, P = .010), respectively. Significant correlations between NFL and insulin, TC, HDL-C, TG, VLDL-C, and BMI were found. NFL (9.38 vs 3.08) and tau (439.28 vs 281.58) concentrations and PASI values (23.94 vs 14.18) in patients with disease onset before 40 years were significantly higher than that of the patients with disease onset after 40 years. C-reactive protein (CRP) was significantly correlated with BMI (r = .449, P < .001), LDL-C (r = .240, P = .026), TG (r = .244, P = .024), and VLDL-C (r = .241, P = .025) in patients with psoriasis. CONCLUSIONS: Increased serum NFL and tau protein levels and the presence of positive correlations between NFL, tau protein and PASI score show cognitive decline risk may be higher in moderate-to-severe psoriasis.

α-Lipoic Acid Ameliorates The Changes in Prooxidant-Antioxidant Balance in Liver and Brain Tissues of Propylthiouracil-Induced Hypothyroid Rats.

OBJECTIVE: There are controversial data about the prooxidant-antioxidant balance in hypothyroidism. We aimed to investigate the effect of α-lipoic acid (ALA) on oxidative stress parameters in the liver and brain of propylthiouracil (PTU)-induced hypothyroid rats. MATERIALS AND METHODS: In this experimental study, PTU (500 mg/L) was given to rats in drinking water for 10 weeks. ALA (0.2% in diet) alone and together with thyroxine (T4, 20 µg/kg body weight, s.c) were given to hypothyroid rats in the last 5 weeks of the experimental period. The levels of reactive oxygen species, malondialdehyde, protein carbonyl, ferric reducing antioxidant power (FRAP) and glutathione (GSH) levels, superoxide dismutase, and GSH peroxidase activities were determined in the liver and brain of rats. Histopathological examinations were also performed. RESULTS: Prooxidant parameters were increased in the brain but not liver in hypothyroid rats. ALA treatment alone lowered enhanced brain oxidative stress in hypothyroid rats. Also, ALA was found to ameliorate the changes as a result of oxidative stress arising from T4 replacement therapy. CONCLUSION: Our results indicate that ALA alone and together with T4 may be useful in reducing oxidative stress in thyroid dysfunctions.

Dietary curcumin and capsaicin: Relationship with hepatic oxidative stress and apoptosis in rats fed a high fat diet.

BACKGROUND: Apoptosis plays a major role in fatty liver disease. High-fat diets are related to the onset of fatty liver disease and hepatic oxidant-antioxidant imbalance. Curcumin and capsaicin are somewhat beneficial in reducing hepatic triglycerides; this is most likely because they are known to downregulate reactive oxygen species (ROS) and apoptosis. OBJECTIVES: The aim of this study was to investigate the effects of curcumin and capsaicin on apoptosis through the oxidative effect in an animal model of fatty liver disease. MATERIAL AND METHODS: Male Sprague Dawley rats were fed a normal control diet, a high-fat diet (HFD; 60% of total calories from fat), a HFD+curcumin (1.5 g curcumin/kg HFD), a HFD+capsaicin (0.15 g capsaicin/kg HFD), or a HFD+curcumin+capsaicin (1.5 g curcumin and 0.15 g capsaicin/kg HFD). Liver lysate levels of BAX, Bcl-2 and caspase-3 were determined via immunoblotting. Caspase-3 activity was measured with a colorimetric caspase-3 measurement kit. Total antioxidant status (TAS) and total oxidant status (TOS) were assayed using commercial kits. The generation of hepatic ROS was measured with fluorimetry. Fragmentation of DNA was detected using the TUNEL method. RESULTS: High-fat diet caused increased expression of BAX and caspase-3, as well as increased TOS and caspase-3 activity, but decreased expression of Bcl-2. HFD+curcumin+capsaicin caused decreased BAX, caspase-3, TOS, and ROS levels as compared to HFD, but increased TAS and Bcl-2. A HFD +curcumin+capsaicin also decreased the number of TUNEL-positive cells. CONCLUSIONS: These results suggest that supplementation with curcumin and capsaicin balances the hepatic oxidant-antioxidant status and may have a protective role in the apoptotic process in an HFD-induced fatty liver model.

Effect of dietary curcumin and capsaicin on testicular and hepatic oxidant-antioxidant status in rats fed a high-fat diet.

This study investigated the effects of curcumin and capsaicin on testicular and hepatic oxidant-antioxidant status in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats were divided into 5 groups (8 rats per group). The control group was fed a normal control diet (standard laboratory chow), the HFD group was fed HFD (60% of total calories from fat), the HFD+CUR group received HFD supplemented with curcumin (1.5 g curcumin/kg HFD), the HFD+CAP group was given HFD supplemented with capsaicin (0.15 g capsaicin/kg HFD), and the HFD+CUR+CAP group received HFD supplemented with curcumin and capsaicin for 16 weeks. Hepatic and testicular thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS), glutathione (GSH) levels, glutathione transferase activity, and Cu-Zn superoxide dismutase, glutathione peroxidase, and catalase protein expression and enzyme activities were measured. Protein expression was determined by Western blotting. GSH levels and antioxidant enzyme activities were measured with colorimetric methods. HFD slightly increased hepatic and testicular oxidative stress parameters. GSH levels did not change between groups. TBARS and ROS levels were significantly reduced in the HFD+CUR+CAP group compared with the HFD group. Liver and testis antioxidant enzyme activities and expression increased significantly with combined capsaicin and curcumin treatment. Curcumin and capsaicin treatment attenuated testicular and hepatic oxidative stress and enhanced the antioxidant defense system. The combination of capsaicin and curcumin with HFD seems to have some remarkable and beneficial effects on testicular oxidative damage in the fatty liver rat model.

The endothelin 1 and endothelin receptor A gene polymorphisms increase the risk of developing papillary thyroid cancer.

The endothelin (EDN) axis (EDN1 and EDN1 receptor A, EDNRA) is involved in cellular growth, differentiation, invasiveness, and tumor progression in several cancers. We wanted to examine the possible impact of single nucleotide polymorphisms (SNPs) of EDN1 and EDNRA genes on papillary thyroid cancer (PTC) development and general characteristics of PTC. Study population consist of 113 PTC patients and 185 controls. EDN1 (G5665T, T-1370G) and EDNRA (C TT70G, G-231A) SNPs were investigated by real-time PCR. The GG genotype of EDNRA + 70 SNP was associated with threefold increased PTC risk (p = 0.01), and the combined CG + GG genotype was 2.48 fold higher among PTC patients compared to controls. The variant EDNRA - 231 allele was overrepresented in PTC patients according to controls (p = 0.05). The combined GT + TT genotype of EDN1 5665 SNP was related with late (age after 40 years) PTC onset (p = 0.04), and was more prominent among male patients with PTC according to females (p = 0.03). No significant associations between PTC and - 1370 SNP were found. There were no relationships between laboratory parameters and investigated polymorphisms. The EDNRA + 70 SNP was associated with PTC development. The EDN1 5665 SNP was linked with increased risk for late PTC onset and was more prominent among male patients with PTC.

Effect of betaine treatment on the regression of existing hepatic triglyceride accumulation and oxidative stress in rats fed on high fructose diet.

We investigated whether betaine has any regressive effect on existing high fructose diet (HFrD)-induced insulin resistance, dyslipidemia, inflammation as well as hepatic steatosis and oxidative stress. Rats were fed a HFrD containing 60% fructose for 8 weeks. After 8 weeks, rats were divided into two groups and fed a control diet for an additional 4-week period (regression groups). One of the regression groups received drinking water containing betaine (1%; w/v), having antioxidant and anti-inflammatory actions. HFrD feeding caused insulin resistance, elevated triglyceride (TG) and tumor necrosis factor-alfa (TNF-α) levels, alanine aminotransferase (ALT) and aspartate transaminase (AST) activities in serum. This diet increased hepatic TG, thiobarbituric acid reactive substances (TBARS) and diene conjugate (DC) levels, decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Marked macro-vesicular steatosis were detected. Serum TNF-α and ALT, hepatic TG, TBARS and DC levels and steatosis scores decreased in regression period of HFrD-fed rats. Additionally, serum TNF-α, hepatic TG, TBARS and DC levels significantly lower in betaine-treated regressed rats than non-treated regressed group. Our results indicate that betaine treatment may accelerate regression of HFrD-induced hepatic TG accumulation and oxidative stress in rats.

The effect of resveratrol on glycation and oxidation products in plasma and liver of chronic methylglyoxal-treated rats.

BACKGROUND: Methylglyoxal (MG) is a highly reactive dicarbonyl compound. It is produced by processes like glycolysis, glucose autooxidation, lipid peroxidation, and protein glycation. It is a major precursor of advanced glycation end products (AGE). It also exacerbates oxidative stress in the organism. Although there are some in vitro studies investigating the effect of resveratrol (RES) as an antioxidant and antiglycating agent on MG-induced toxicity, in vivo effect of RES is unknown. Therefore, we aimed to investigate the efficiency of RES in chronic MG-treated rats. METHODS: Rats were given incrementally increased doses (100-300 mg/kg) of MG in drinking water for ten weeks. RES (10 mg/kg ip) was administered together with MG. Reactive oxygen species (ROS) formation, thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels as well as ferric reducing antioxidant power (FRAP) values were determined in plasma and liver. RESULTS: Significant increases in plasma TBARS, PC, AOPP and AGE and fructosamine levels were detected in MG-treated rats. However, plasma ROS and FRAP levels remained unchanged. Hepatic ROS, TBARS, PC and AOPP, but not AGE and FRAP levels were also increased in MG-treated rats. RES treatment diminished high levels of plasma PC, AOPP and AGE levels in MG-treated rats. Additionally, significant decreases in hepatic ROS, TBARS, PC and AOPP levels together with histopatological amelioration were detected due to RES treatment in MG-treated rats. CONCLUSIONS: Our results indicate that RES may be considered as a protective agent against glycoxidative stress generated by in vivo MG treatment.

N-Acetylcysteine supplementation decreased brain lipid and protein oxidations produced by experimental homocysteine thiolactone exposure: Relevance to neurodegeneration.

High levels of homocysteine (Hcy) have neurotoxic effects. Homocysteine thiolactone (HcyT), a thioester of Hcy, plays a role in Hcy-induced toxicity. In this study, effects of HcyT treatment (500 mg/kg body weight/day in drinking water) for 6 weeks on serum Hcy levels and brain prooxidant-antioxidant balance were investigated in rats. The effect of N-acetylcysteine (NAC) treatment (1 g/kg body weight/day in chow) for 6 weeks on HcyT-induced neurotoxicity was evaluated. Reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), diene conjugate (DC), protein carbonyl (PC) and advanced oxidation protein products (AOPP) were determined in the brain tissue. Ferric reducing antioxidant power (FRAP) and non-protein sulfydryl groups (NPSH) levels as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were also measured to evaluate the antioxidant potential of brain the tissue. HcyT elevated serum Hcy levels and brain ROS, TBARS, DC, PC and AOPP levels. However, HcyT did not affect FRAP levels and SOD, and GSH-Px activities. NAC treatment decreased serum Hcy and brain ROS, TBARS, DC, PC and AOPP levels in HCyT-treated rats. Our results indicate that NAC supplementation may be effective in decreasing serum Hcy levels and HcyT-induced oxidative stress in brain of rats.

Carnosine Treatment Diminished Oxidative Stress and Glycation Products in Serum and Tissues of D-Galactose-Treated Rats.

BACKGROUND: Chronic administration of D-galactose (GAL) induces changes that resemble natural aging in rodents. Oxidative stress and Advanced Glycation End products (AGE) formation play a role in GAL-induced aging. Carnosine (CAR; ß-alanyl-L-histidine) has antioxidant and anti-glycating actions and may be a potential therapeutic agent in aging due to these properties. The effect of CAR supplementation on AGE levels and oxidative stress parameters was investigated in serum, liver and brain tissues in GAL-treated rats. METHODS: GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) was applied to male rats for two months. AGE, Advanced Oxidized Protein Products (AOPP), Protein Carbonyl (PC) and Malondialdehyde (MDA) levels together with Reactive Oxygen Species (ROS) formation and Ferric Reducing Antioxidant Power (FRAP) values were determined. RESULTS: GAL treatment elevated AGE levels, ROS formation and protein and lipid oxidation products in serum and examined tissues. CAR treatment was observed to decrease significantly glycooxidative stress in serum, liver and brain tissues of GAL-treated rats. CONCLUSION: Our results indicate that CAR may be useful for decreasing oxidative stress and glycation products in GAL-induced aging model in rats.

Carnosine decreased oxidation and glycation products in serum and liver of high-fat diet and low-dose streptozotocin-induced diabetic rats.

High-fat diet (HFD) and low-dose streptozotocin (STZ)-treated rats provide useful animal model for type II diabetes mellitus. Oxidative stress and advanced glycation end products (AGEs) play a role in the development of diabetic complications. Carnosine (CAR) has anti-oxidant and anti-glycating properties. We investigated the effects of CAR on oxidation and glycation products in HFD+STZ rats. Rats were fed with HFD (60% of total calories from fat) for 4 weeks, and then a single dose of STZ (40 mg/kg; i.p.) was applied. Rats with blood glucose levels above 200 mg/dl were fed with HFD until the end of the 12th week. CAR (250 mg/kg body weight; i.p.; five times a week) was administered to the rats for the last four weeks. CAR significantly decreased serum triglyceride (TG) (57.7%), cholesterol (35.6%) levels and hepatic marker enzyme activities of HFD+STZ rats. It significantly reduced serum reactive oxygen species (ROS) (23.7%), AGEs (13.4%) and advanced oxidized protein products (AOPP) (35.9%) and hepatic TG (59%), ROS (26%), malondialdehyde (MDA) (11.5%), protein carbonyl (PC) (19.2%) and AGE (20.2%) levels. Liver steatosis and hepatocyte ballooning were also significantly reduced. However, CAR treatment did not alter serum glucose and blood glycated haemoglobin and hepatic anti-oxidant enzyme activities/mRNA expressions in HFD+STZ rats. Our results indicate that CAR decreased accumulation of oxidation and glycation products, such as MDA, AGE, AOPP and PC in the serum and liver and ameliorated hepatic dysfunction in HFD+STZ rats. This effect may be related to its anti-oxidative, anti-glycating, and anti-lipogenic potential.

Association of Leukotrichia in Vitiligo and Asp148Glu Polymorphism of Apurinic/Apyrimidinic Endonuclease 1.

BACKGROUND: Oxidative stress and increased DNA damage have been implicated in the etiopathogenesis of vitiligo. Oxidative DNA damage is mainly repaired by the base excision repair (BER) pathway. AIM: We sought to determine whether polymorphisms in DNA repair genes may have a role in the pathogenesis of vitiligo. MATERIALS AND METHODS: We conducted a study including 100 patients with vitiligo and age- and sex-matched 193 control subjects to examine the role of single-nucleotide polymorphisms of BER genes, human 8-oxoG DNA N-glycosylase 1 (codon 326), apurinic/apyrimidinic endonuclease 1 (APE1) (codon 148), and X-ray repair cross-complementing group 1 (codon 399) as risk factors for vitiligo. These polymorphisms were determined by quantitative real-time polymerase chain reaction and melting curve analysis. RESULTS: No significant association was observed between the variant alleles of studied genes and vitiligo. CONCLUSION: However, we showed that the presence of APE1 148Glu variant allele is associated with leukotrichia. This preliminary study suggests that APE1 (codon 148) polymorphism may play a role in vitiligo pathogenesis.

Antiglycation and anti-oxidant efficiency of carnosine in the plasma and liver of aged rats.

AIM: Increases in oxidative stress and advanced glycation end-products (AGE) formation play an important role in the pathogenesis of aging. Carnosine (CAR; ß-alanyl-L-histidine) has anti-oxidant and antiglycating properties. We investigated the effect of CAR supplementation on AGE levels, and protein and lipid oxidation products in the serum and liver tissue in aged rats. METHODS: Young (3 months-of-age) and aged (20 months-of-age) rats were injected with CAR (250 mg/kg/daily; i.p.; 5 days per week) for 2 months. At the end of this period, AGE, protein carbonyl, advanced oxidized protein products, and malondialdehyde levels were determined in the serum and liver tissue. Furthermore, reactive oxygen species formation and ferric reducing anti-oxidant power values were measured. RESULTS: AGE, malondialdehyde, protein carbonyl and advanced oxidized protein products levels, and reactive oxygen species formation were higher in the serum and liver tissue of aged rats compared with young rats. CAR treatment was observed to significantly decrease AGE, malondialdehyde, protein carbonyl and advanced oxidized protein products levels, and reactive oxygen species formation in the serum and liver of aged rats. CONCLUSIONS: These results clearly show that CAR might be useful for decreasing glycoxidant stress in aged rats. Geriatr Gerontol Int 2017; 17: 2610-2614.

Effect of Carnosine on Renal Function, Oxidation and Glycation Products in the Kidneys of High-Fat Diet/Streptozotocin-Induced Diabetic Rats.

High fat diet (HFD) and low dose of streptozotocin (STZ)-treated rats provide an animal model for type 2 Diabetes Mellitus (T2DM). Oxidative stress plays a role in the development of diabetic complications. Carnosine (CAR) has antioxidant and antiglycating properties. We investigated effects of CAR on renal function, oxidation and glycation products in HFD+STZ-rats. Rats were fed with HFD (60% of total calories from fat) for 4 weeks and then a single dose STZ (40 mg/kg; i.p.) was applied. Rats with blood glucose levels above 200 mg/dL were fed with HFD until the end of the 12th week. CAR (250 mg/kg body weight; i.p.; 5 times a week) was administered to rats for the last 4 weeks. Glycated hemoglobin (HbA1c), glucose, lipids, and andrenal function tests in serum as well as reactive oxygen species, malondialdehyde, protein carbonyl, advanced oxidation protein products, advanced glycation end products (AGEs), antioxidant power, and antioxidant enzyme activities and their mRNA expressions in kidneys were determined. CAR treatment did not alter glucose and HbA1c, but it decreased serum lipids, creatinine, and urea levels in HFD+STZ rats. Oxidation products of lipids and proteins and AGEs levels decreased, but antioxidant enzyme activities and their mRNA expressions remained unchanged due to CAR treatment. Our results indicate that CAR treatment alleviated renal function and decreased accumulation of oxidation and glycation products in kidneys in HFD+STZ-rats.

The effect of carnosine on methylglyoxal-induced oxidative stress in rats.

Methylglyoxal (MG) is generated from glycolytic metabolites, lipid peroxidation, glucose autooxidation and protein glycation. It is a prooxidant inducing oxidative stress and formation of advanced glycation end products (AGE). Effect of carnosine (CAR) as an antioxidant on toxicity due to MG has generated interest. In this study, rats were given incrementally increased doses (100-300 mg/kg) of MG in drinking water for ten weeks. CAR (250 mg/kg i.p.) was administered with MG. Plasma thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels were elevated by MG, and CAR decreased PC, AOPP and AGE levels. MG increased liver reactive oxygen species (ROS), TBARS, PC and AOPP levels, which were decreased by CAR. Thus, in vivo role of CAR on chronic MG administration was observed to suppress the generated hepatic and plasma oxidative stress.

The effect of N-acetylcysteine supplementation on serum homocysteine levels and hepatic and renal oxidative stress in homocysteine thiolactone-treated rats.

The effect of N-acetylcysteine (NAC) (1 g/kg body weight/day) on serum homocysteine (Hcy) levels, insulin resistance (IR), and hepatic and renal prooxidant-antioxidant balance was evaluated in rats treated with homocysteine thiolactone (HcyT) (500 mg/kg body weight/day for 6 weeks). Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione, ferric reducing antioxidant power, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined in the liver and kidney. HcyT elevated serum Hcy levels and caused IR, but liver and kidney function tests remained unchanged. HcyT increased ROS and MDA without any change in hepatic antioxidants, but it elevated renal SOD and GSH-Px activities. NAC decreased serum Hcy, hepatic and renal ROS and MDA levels, and renal SOD and GSH-Px activities in rats with high Hcy levels. However, it did not ameliorate IR. Our results indicate that NAC supplementation may be effective in decreasing Hcy levels and Hcy-induced hepatic and renal oxidative stress.

High circulating levels of sICAM-1 and sVCAM-1 in the patients with Hashimoto's thyroiditis.

OBJECTIVE: To investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels are increased in euthyroid patients with Hashimoto's thyroiditis (HT) and whether they are associated with thyroid autoimmunity and metabolic parameters. DESIGN: Cross-sectional. SUBJECTS AND METHODS: In total, 80 euthyroid patients with HT and 80 age- and body mass index (BMI)-matched control participants were included. Serum sICAM-1, sVCAM-1, free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), fasting blood glucose (FBG), insulin, and lipid levels and homeostasis model assessment for insulin resistance (HOMA-IR) were assessed in all participants. RESULTS: The patients with HT had significantly higher levels of sICAM-1 and sVCAM-1 than controls (both p < 0.001). The difference was sustained after adjustment for TSH and levothyroxine use. Regression analysis demonstrated that sICAM-1 was related to anti-TPO (p < 0.001), and sVCAM-1 was related to both anti-TPO and-TG (p < 0.001 and p = 0.03, respectively); this relationship was sustained after adjustment for age and BMI. Although FBG and HOMA-IR were higher in the HT group, logistic regression analysis revealed that there was no effect of anti-TPO, anti-TG, sICAM-1, sVCAM-1, and C-reactive protein (CRP) on the occurrence of high FBG and high HOMA-IR. CONCLUSION: sICAM-1 and sVCAM-1 levels were significantly elevated in the patients with euthyroid HT and correlated closely with thyroid autoimmunity. However, soluble adhesion molecules had no relation with glucose metabolism parameters in the HT patients.

Vascular endothelial growth factor G+405C polymorphism may contribute to the risk of developing papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Vascular endothelial growth factor (VEGF) is a mediator implicated with cell proliferation, differentiation and migration, and monocyte/macrophage chemotaxis. In present study, we aimed to investigate the relationship between VEGF gene polymorphisms (G+405C, T-460C, and A-2578C) and PTC susceptibility. METHODS: DNA was isolated from peripheral blood leukocytes of 127 patients with PTC and 203 healthy controls. Genotyping was performed by real-time PCR. Association of genotypes with susceptibility of PTC was analyzed with multivariate logistic regression adjusted for age, gender and smoking status. RESULTS AND CONCLUSION: In G+405C polymorphism, the frequencies of C allele (related with increased VEGF production) and combined CG+CC genotype were found to be higher (3.5 and 5-fold, respectively) among patients with PTC than controls (P<.001). However, VEGF T-460C and A-2578C polymorphisms are not associated with PTC risk. There was no relationship between VEGF polymorphisms and clinical/laboratory parameters of PTC. Haplotype analysis demonstrated that there was a strong linkage disequilibrium (LD) between -460/-2578 (D'=.89, r2 =.79), weak LD between +405/-460 (D'=.422, r2 =.035), and +405/-2578 (D'=.43, r2 =.038) locuses. Additionally, the +405/-460/-2578 GTA haplotype was found to be protective, whereas CTA haplotype to be related with increased PTC risk. As a conclusion, we suggest that VEGF G+405C polymorphism is associated with increased risk of PTC.

High-fat diet plus carbon tetrachloride-induced liver fibrosis is alleviated by betaine treatment in rats.

Steatosis, the first lesion in non-alcoholic fatty liver disease (NAFLD), may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis predisposes the liver to oxidative stress, inflammation, and cytokines. Betaine (BET) has antioxidant, antiinflammatory and hepatoprotective effects. However, the effects of BET on liver fibrosis development are unknown. Rats were treated with high-fat diet (60% of total calories from fat) for 14weeks. Carbon tetrachloride (0.2mL/kg; two times per week; i.p.) was administered to rats in the last 6weeks with/without commercial food containing BET (2%; w/w). Serum liver function tests and tumor necrosis factor-α, insulin resistance, hepatic triglyceride (TG) and hydroxyproline (HYP) levels and oxidative stress parameters were determined along with histopathologic observations. Alpha-smooth muscle-actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and type I collagen (COL1A1) protein expressions and mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were evaluated. BET decreased TG and HYP levels, prooxidant status and fibrotic changes in the liver. α-SMA, COL1A1 and TGF-ß1 protein expressions, MMP-2, TIMP-1, and TIMP-2 mRNA expressions diminished due to BET treatment. BET has an antifibrotic effect and this effect may be related to its antioxidant and antiinflammatory actions together with suppression on HSC activation.