The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines.

ß-blockers having specific affinities to ß-adrenergic receptors are routinely used to treat cardiovascular problems. Additionally, it has been demonstrated that these drugs can be effective in treating apoptosis-related diseases. The current study was conducted to investigate the cytotoxic and apoptotic effects of ß-1 selective esmolol, ß-2 selective ICI-118,551, and non-selective nadolol blockers on the cancerous and healthy lung cells. MTT test was used to evaluate cytotoxicity. Apoptotic actions were examined by using Annexin V-FITC/PI assay, JC-1 staining, ROS test, and the determination of the caspase-4 and -9, Bcl-2, Bax, Bax/Bcl-2, and JNK levels. Although the MRC-5 showed greater resistance than A549 cells, the ß-blockers at 150-250 µM exhibited different levels of cytotoxic effect on both lung cell lines. Esmolol was found to be the most ineffective blocker and the increases in Bcl-2 protein levels were appeared to be effective in resistance to this drug. The increases in reactive oxygen species (ROS) together with the increase in caspase-4 and Bax protein levels have been shown to play a role in ICI-118,551 induced lung cell death. Nadolol was the most effective blocker increasing the total apoptotic cell population in both lung cells, which was based on both mitochondrial and endoplasmic reticulum stress. When the selectivities of the ß-blockers are considered, it seems that ß-2 specific antagonism predominantly mediated the death of lung cells, and the overwhelming factors causing apoptosis mainly varied depending on the selectivity of the blockers.

The sulfite molecule enhances homocysteine toxicity in SH-SY5Y cells.

Homocysteine (hcy) is an amino acid that contains sulfur species. In healthy individuals, plasma hcy levels are low. The aim of this study was to investigate the potential neurotoxic effects of hcy and sulfite (sft) molecules alone and in their combination, and also to identify the relationship of these substances on oxidative stress. SH-SY5Y cells were used as an invitro neurodegenerative disease model. The SH-SY5Y cells were treated with various concentrations of hcy alone, sft alone (final concentrations in the well were 10-250 µM and 0.1-5 mM, respectively) and a combination of both (hcy + sft). Their cytotoxicity and genotoxic effects were investigated using the XTT test and Comet assay and, their impact on oxidative stress was examined using total antioxidant-oxidant status (TAS-TOS) kits. The highest toxic doses of hcy and sft were found to be 250 µM and 5 mM, respectively, but the maximum toxic effect was observed for hcy + sft (p < 0.001). In addition, an increase in DNA damage was evident in all groups, but maximal damage was inflicted using in hcy + sft (p < 0.001). The oxidative stress index was significantly increased in hcy + sft (p < 0.05). Determining the increase in sft and hcy levels may contribute to delaying the occurrence of diseases before symptoms of neurodegenerative disease appear.

Oxidative Stress and Genotoxicity in Pterygium: A Systemic Investigation.

OBJECTIVES: To perform a systemic investigation on oxidative stress and DNA damage in patients with primary pterygium. METHODS: This prospective cross-sectional study included 32 patients with primary pterygium (60.1±2.0 years of age) and 33 age- and sex-matched (58.8±2.2 years of age) control subjects (P>0.05). A commercial kit was used for measuring serum total oxidant status (TOS) and total antioxidant status (TAS). The comet assay was performed after lymphocyte isolation from venous blood to quantitate DNA damage. Tail length (TL), tail intensity (TI), and tail moment (TM) were used for statistical analysis as parameters of DNA damage. RESULTS: In the pterygium group, TOS and TAS were significantly higher when compared with those of the control group (P=0.019 and P=0.005, respectively). In terms of DNA damage, patients with pterygium had higher TL, TI, and TM than in the control subjects (P<0.0001 for all). CONCLUSIONS: Although current literature focuses on local factors in pterygium pathogenesis, patients with pterygium seem to have increased systemic oxidative status (and compensatory antioxidant response) and genotoxicity, which might create a predisposition for pterygium development.

Contribution of Heme Oxygenase 2 to Blood Pressure Regulation in Response to Swimming Exercise and Detraining in Spontaneously Hypertensive Rats.

BACKGROUND We aimed to determine the effects of exercise followed by detraining on systolic blood pressure (SBP), heme oxygenase 2 (HO-2) expression, and carboxyhemoglobin (COHb) concentration in spontaneously hypertensive rats (SHR) to explain the role of carbon monoxide (CO) in this process. MATERIAL AND METHODS Animals were randomized into exercised and detrained groups. Corresponding sedentary rats were grouped as Time 1-2. Swimming of 60 min/5 days/week for 10 weeks was applied. Detraining rats discontinued training for an additional 5 weeks. Gene and protein expressions were determined by real-time PCR and immunohistochemistry. RESULTS Aorta HO-2 histological scores (HSCORE) of hypertensive rats were lower, while SBP was higher. Swimming caused enhancement of HO-2 immunostaining in aorta endothelium and adventitia of SHR. Exercise induced elevation of blood COHb index in SHR. Synchronous BP lowering effect of exercise was observed. HO-2 mRNA expression, HSCORE, and blood COHb index were unaltered during detraining, while SBP was still low in SHR. CONCLUSIONS CO synthesized by HO-2 at least partly plays a role in SBP regulation in the SHR- and BP-lowering effect of exercise. Regular exercise with short-term pauses may be advised to both hypertensives and individuals who are at risk.

N-acetylcysteine supplementation reduces oxidative stress for cytosine arabinoside in rat model.

Cytosine arabinoside (ARA-C) is a pyrimidine analog that may cause keratoconjunctivitis when used in high doses. The underlying mechanism may be the increased amounts of reactive oxygen radicals that may damage the DNA synthesis of corneal and conjunctival epithelial cells. Topical corticosteroids are one of the prophylactic treatments for keratoconjunctivitis induced by ARA-C. Forty Wistar-type albino rats were included in this study the rats were divided into four groups. The first group (Group 1) received only ARA-C, the second group (Group 2) received ARA-C and N-acetylcysteine (NAC), the third group (Group 3) received only NAC and the fourth group (Group 4) was the control group. The total oxidant status (TOS), the total antioxidant capacity and the oxidative stress index (OSI) measurements of the cornea and the conjunctiva were evaluated in these four groups. The mean TOS and OSI value was the highest in Group 1 and the lowest in Group 3. The differences in TOS and OSI values were statistically significant between Group 1 and Group 2. There are decreases in TOS and OSI values in rats which received ARA-C with NAC administration. NAC may have a protective effect on ARA-C-induced keratoconjunctivitis.

Detraining reverses exercise-induced improvement in blood pressure associated with decrements of oxidative stress in various tissues in spontaneously hypertensive rats.

This study aimed to investigate the effects of moderate intensity swimming exercise (10 weeks) followed by detraining (for five and 10 weeks) on oxidative stress levels of heart, lung, kidney, and liver tissues and systolic blood pressure (SBP) of spontaneously hypertensive rats (SHR). SHR and control rats were randomized into sedentary, exercised, detrained (5 weeks) and late-detrained (10 weeks) groups. Corresponding sedentary rats were grouped as time 1-2-3. Exercise of 60 min, 5 days/week/10 weeks was applied. Detraining rats underwent the same training protocol and then discontinued training during next 5, 10 weeks. SBP was measured by tail-cuff method. Tissue total oxidant/antioxidant status was measured using a commercial kit and oxidative stress index (OSI) was calculated. Exercise training slightly decreased tissue OSI of SHR and reduced SBP of both groups. Tissue OSI of SHR were higher than WKY and aging resulted in increment of oxidants in groups. detraining yielded time-dependent increments in oxidative stress of all tissues and SBP of both rat groups. Although short-term cessations may be tolerated, our results emphasize the importance of exercising as a way of life for cardiovascular well-being in hypertensives or in individuals who are genetically under risk of hypertension.

Valproic acid inhibits the proliferation of SHSY5Y neuroblastoma cancer cells by downregulating URG4/URGCP and CCND1 gene expression.

Valproic acid (VPA), used for the treatment of epilepsy and bipolar disorder, regulates several signaling pathways in brain cells. The up-regulated gene 4 (URG4/URGCP) is a novel gene located on 7p13. URG4/URGCP stimulates cyclin D1 (CCND1) mRNA expression, and URG4/URGCP silencing diminishes CCND1 mRNA expression in HepG2 cells. This study was performed to investigate the anti-cancer mechanism of action of VPA by analyzing the expression of novel gene URG4/URGCP, CCND1, p21, p53, p65 (RelA), Bax, and Bcl-2 in SHSY5Y neuroblastoma (NB) cancer cells. Cytotoxic effects of VPA in SHSY5Y were noticed in time and dose dependent manner with the IC50 doses within the range of 0.5-10 mM. IC50 doses in the SHSY5Y were detected as 7.5 mM. Expression profiles were determined by semi quantitative RT-PCR and URG4/URGCP protein change by western blot analysis. Our results suggest that VPA induces cell cycle arrest in SHSY5Y due to the decrease in URG4/URGCP, CCND1 gene expression and the increase in p65. To conclude, VPA may be a prospective agent for the treatment of NB as a single agent or in combination with other drugs. Thus, more studies should be designed to find a safe dose with the best effects of VPA.

Regulation of URG4/URGCP and PPARα gene expressions after retinoic acid treatment in neuroblastoma cells.

Neuroblastoma (NB), originating from neural crest cells, is the most common extracranial tumor of childhood. Retinoic acid (RA) which is the biological active form of vitamin A regulates differentiation of NB cells, and RA derivatives have been used for NB treatment. PPARα (peroxisome proliferator-activated receptor) plays an important role in the oxidation of fatty acids, carcinogenesis, and differentiation. URG4/URGCP gene is a proto-oncogene and that overexpression of URG4/URGCP is associated with metastasis and tumor recurrence in osteosarcoma. It has been known that URG4/URGCP gene is an overexpressed gene in hepatocellular carcinoma and gastric cancers. This study aims to detect gene expression patterns of PPARα and URG4/URGCP genes in SH-SY5Y NB cell line after RA treatment. Expressions levels of PPARα and URG4/URGCP genes were analyzed after RA treatment for reducing differentiation in SH-SY5Y NB cell line. To induce differentiation, the cells were treated with 10 µM RA in the dark for 3-10 days. Gene expression of URG4/URGCP and PPARα genes were presented as the yield of polymerase chain reaction (PCR) products from target genes compared with the yield of PCR products from the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. SH-SY5Y cells possess small processes in an undifferentiated state, and after treatment with RA, the cells developed long neurites, resembling a neuronal phenotype. PPARα gene expression increased in RA-treated groups; URG4/URGCP gene expression decreased in SH-SY5Y cells after RA treatment compared with that in the control cells. NB cell differentiation might associate with PPARα and URG4/URGCP gene expression profile after RA treatment.

The effect of L-carnosine on erythrocyte deformability and aggregation according to the cell age in young and aged rats.

This study aimed to investigate alterations in hemorheology induced by L-carnosine, an anti- oxidant dipeptide, and to determine their relationship to oxidative stress in density-separated erythrocytes of aged and young rats. 28 male Sprague Dawley rats were divided into 4 groups as aged (Aca), young (Yca) L-carnosine groups (250 mg/kg L-carnosine, i.p.) and aged (As), young (Ys) control groups (saline, i.p.). Density separation was further performed to these groups in order to separate erythrocytes according to their age. Blood samples were used for the determination of erythrocyte deformability, aggregation; and oxidative stress parameters. Erythrocyte deformability of Yca group measured at 0.53 Pa was lower than Aca group. Similarly, deformability of least-dense (young) erythrocytes of Yca group was decreased compared to least-dense erythrocytes of Aca groups. Total antioxidant capacity (TAC) of Aca group was higher and oxidative stress index (OSI) lower than As group. Although L-carnosine resulted in an enhancement in TAC of aged rats, this favorable effect was not observed in erythrocyte deformability and aggregation in the dose applied in this study.

Expression of URG4/URGCP, Cyclin D1, Bcl-2, and Bax genes in retinoic acid treated SH-SY5Y human neuroblastoma cells.

Retinoic acid (RA) plays important roles in development, growth, and differentiation by regulating the expression of its target genes. The pro-apoptotic Bax gene may form channels through oligomerization in the mitochondrial membrane and facilitate the cytosolic release of cytochrome c. The anti-apoptotic Bcl-2 gene can inhibit this process. Up-regulated gene 4/Upregulator of cell proliferation (URG4/URGCP) is a novel gene located on 7p13. URG4/URGCP also stimulates cyclin D1 (CCND1) mRNA expression, and RNAi-mediated URG4/URGCP silencing diminishes CCND1 mRNA expression in HepG2 cells. In this study, the effects of RA treatment on URG4/URGCP, CCND1, Bcl-2 and Bax gene expression changes in undifferentiated and differentiated SHSY5Y neuroblastoma cells was analyzed. SHSY5Y cells were cultured in the appropriate conditions. To induce differentiation, the cells were treated with 10 micromolar RA in the dark for 3-10 days. SHSY5Y cells possess small processes in an undifferentiated state, and after treatment with RA, the cells developed long neurites, resembling a neuronal phenotype. Total RNA was isolated with Tri-Reagent. Expression profiles of the target genes were determined by semi-quantitative RT-PCR. According to the results, Bcl-2 and CCND1 gene expression levels were increased, while URG4/URGCP and Bax gene expression was decreased in RA treated cells compared to the control cells. Our preliminary results suggest that RA may induce cell proliferation and escape apoptosis using a novel pathway by the URG4/URGCP gene. Further investigations are needed to clarify more direct transcriptional targets of RA signaling and the interaction of RA pathways with other pro-regenerative signals.

The anticancer effects of thymol on HepG2 cell line.

There is an increasing incidence of liver cancer, which is a hazard for global health. The present study was designed to evaluate possible cytotoxic, genotoxic, apoptotic, oxidant and antioxidant effects of thymol on hepatocellular carcinoma (HepG2) cell line. The cytotoxic effect of thymol on HepG2 cell line was determined by XTT test. We also used the HUVEC cell line to show whether thymol damages healthy cells. Oxidative stress level was determined with Total Oxidant Status (TOS) and Total Antioxidant Status (TAS) measurement kits. Apoptosis of cells was detected in flow cytometry with Annexin V apoptosis kit. Apoptotic gene expressions were analyzed by real-time PCR. Genotoxicity was determined by comet assay, which measures DNA damage. The thymol IC50 dose was found to be 11 µM on HepG2 cell line. This dose had no lethal effect on the healthy HUVEC cell line. While thymol significantly decreased the TOS level, it increased the TAS level significantly in HepG2 cells compared to control. Thymol significantly induced apoptosis in HepG2 cells (apoptosis rate in control group 1%, in thymol group 21%). Thymol did not alter the gene expressions of bax, bcl-2, and casp3, all of which are associated with apoptosis. Statistically significant change in favor of genotoxicity was observed in tail length measurements. Our results suggest that thymol decreases oxidative stress in HepG2 cell line, but it induces apoptosis and genotoxicity.

Effect of insulin on IR and GLP1-R expressions in HT22 cells.

Insulin is a significant growth factor that specifically binds to the insulin receptor (IR) in the brain and then activates the PI3K-AKT pathway. Glucagon-like peptide 1 (GLP-1) has a variety of functions including neuroprotection, support for neurogenesis, and increasing insulin signal. This study aims to investigate the effect of insulin administered to immortalized clonal mouse hippocampal cell line (HT22) at different doses and intervals on IR, insulin receptor A (IRA), insulin receptor B (IRB), and Glucagon-like peptide 1 receptor (GLP1-R) mRNA expression and protein levels. The cells were planted in 6 well plates at a density of 3 × 105/4 × 105. Cells treated with insulin at different concentrations (5, 10, and 40 nM) were collected at 0.5, 2, 8, 16, and 24 h. RT-PCR and western blot analysis were used to measure mRNA expression and protein levels. Our results showed that insulin has short and long-term effects on IR and GLP1-R expression depending on dose and time. These findings may guide future studies targeting IR isoforms and GLP1-R in particular, as well as determining the optimal dose and duration of insulin stimulation in insulin signaling research.

Investigation of fructose consumption on hippocampal insulin and glucagon-like peptide-1 receptors, and metabolic effects in rats.

Objectives: The detrimental effects of high fructose consumption on metabolic health have been extensively studied. However, limited research has focused on the impact of fructose intake on neuroprotective mechanisms, specifically the expression of insulin receptor (INSR) and glucagon-like peptide-1 receptor (GLP-1R) in the hippocampus. Understanding the effects of fructose on these neuroprotective molecules can provide valuable insights into the potential role of fructose in hippocampal dysfunction. The goal of this study is to aim at the basal plasma levels of lipid profile, insulin, GLP-1, and HOMA-IR, as well as the mRNA and protein expression of neuroprotective molecules such as INSR and GLP-1R in Wistar rats fed a high fructose diet. Materials and Methods: Rats were separated into control (C) and high fructose (HF) groups. The HF group was given 20% fructose water to drink for 16 weeks. Results: Fructose ingestion significantly increased abdominal fat (C=1.24±0.08 g, HF=1.79±0.19 g, P<0.05) and plasma triglyceride levels (C=179.22±22.85 µg/ml, HF=242.45±14.45 µg/ml, P<0.05), but had no statistically significant effect on body weight and plasma HDL, LDL, total cholesterol, insulin, and GLP-1 levels (P>0.05). Although INSR mRNA expression in the hippocampus was significantly lower in the HF group compared to the control group (P<0.05), GLP-1R mRNA expression did not differ significantly across the groups (P>0.05). Furthermore, whereas INSR and GLP-1R protein levels in the experimental group were on a declining trend, this trend was not substantially different (P>0.05). Conclusion: These data suggest that fructose consumption may be harmful to the hippocampus by lowering the expression of INSR.

Hemorheological responses to progressive resistance exercise training in healthy young males.

BACKGROUND: This study aimed to explore the effects of progressive resistance exercise training (PRET) on hemorheology. MATERIAL/METHODS: Exercise sessions included 1-3 sets of 8-12 repetitions at 40-60% of 1-repetition maximum (1-RM) for 3 weeks and at 75-80% of 1-RM during weeks 4-12. Red blood cell (RBC) deformability and aggregation were determined by ektacytometry, plasma and whole blood viscosities (WBV) by rotational viscometry. Lactate concentration was evaluated by an analyzer and fibrinogen was evaluated by coagulometry. Plasma total oxidant/antioxidant status was measured by colorimetry. RESULTS: Following an acute increase after exercise on the first day, RBC deformability was elevated during weeks 3 and 4 (p=0.028; p=0.034, respectively). The last exercise protocol applied in week 12 again caused an acute increase in this parameter (p=0.034). RBC aggregation was increased acutely on the first day, but decreased after that throughout the protocol (p<0.05). At weeks 4 and 12 pre-exercise measurements of WBV at standard hematocrit and plasma viscosity were decreased (p=0.05; p=0.041, respectively), while post-exercise values were increased (p=0.005; p=0.04, respectively). Post-exercise WBV at autologous hematocrit measured at week 12 was increased (p=0.01). Lactate was elevated after each exercise session (p<0.05). Fibrinogen was decreased on the third week (p<0.01), while it was increased on the 4th week (p=0.005). Plasma antioxidant status was increased at week 3 (p=0.034) and oxidative stress index was decreased at week 4 (p=0.013) after exercise. CONCLUSIONS: The results of this study indicate that PRET may have positive effects on hemorheological parameters.

The effect of sodium metabisulphite on active avoidance performance in hypercholesterolemic rats.

The purpose of this study was to investigate the effects of hypercholesterolemia and sulphite on active avoidance learning. Male Wistar rats were divided into eight groups as follows: Control (C), Sulphite (S), Vitamin E (E), Sulphite + Vitamin E (SE), Hypercholesterolemia (H), Hypercholesterolemia + Sulphite (HS), Hypercholesterolemia + Vitamin E (HE), and Hypercholesterolemia + Sulphite + Vitamin E (HSE). At the end of the experimental period, the serum cholesterol level (mean ± SD) was significantly higher in H group (111.5 ± 11.11 mg dL(-1) ) as compared to C group (63.5 ± 4.9 mg dL(-1) ). Levels of thiobarbituric acid reactive substances (TBARS) were increased in HS group as compared to C, H, and S groups. Vitamin E reduced TBARS levels in HSE group compared with HS group. Active avoidance results indicated that hypercholesterolemia was associated with learning impairment. Our data clearly revealed that the combination of hypercholesterolemia and sulphite results in exaggerated impairment of active avoidance. Vitamin E improved active avoidance in HSE group compared with HS group. Therefore, the synergistic effect of hypercholesterolemia and sulphite may be associated with a considerable health risk.

The effects of in vivo and ex vivo various degrees of cold exposure on erythrocyte deformability and aggregation.

BACKGROUND: This study aimed to investigate alterations in hemorheology by cold exposure, in vivo and ex vivo, and to determine their relationship to oxidative stress. MATERIAL/METHODS: Rats were divided into 2 in vivo and ex vivo cold exposure groups. The in vivo group was further divided into control (AR), AC (4°C, 2 hours) and ALTC (4°C, 6 hours) subgroups; and the ex vivo group was divided into control (BR) and BC (4°C, 2 hours) subgroups. Blood samples were used for the determination of erythrocyte deformability, aggregation, and oxidative stress parameters. RESULTS: Erythrocyte deformability and aggregation were not affected by 2-hour ex vivo cold exposure. While 2 hour in vivo cold exposure reduced erythrocyte deformability, it returned to normal after 6 hours, possibly due the compensation by acute neuroendocrine response. Six hours of cold exposure decreased aggregation index, and might be an adaptive mechanism allowing the continuation of circulation. Aggregation of ex vivo groups was lower compared to in vivo groups. Cold exposure at various temperatures did not cause alterations in plasma total oxidant antioxidant status and oxidative stress index (TOS, TAS, OSI) when considered together. CONCLUSIONS: Results of this study indicate that the alterations observed in hemorheological parameters due to cold exposure are far from being explained by the oxidative stress parameters determined herein.

Hippocampal neuron number loss in rats exposed to ingested sulfite.

Sulfite, which is continuously formed in the body during metabolism of sulfur-containing amino acids, is commonly used in preservatives. It has been shown that there are toxic effects of sulfite on many cellular components. The aim of this study was to investigate the possible toxic effects of sulfite on pyramidal neurons by counting cell numbers in CA1 and CA2-CA3 subdivisions of the rat hippocampus. For this purpose, male albino rats were divided into a control group and a sulfite group (25 mg/kg). Sulfite was administered to the animals via drinking water for 8 weeks. At the end of the experimental period, brains were removed and neurons were estimated in total and in a known fraction of CA1 and CA2-CA3 subdivisions of the left hippocampus by using the optical fractionator method--a stereological method. Results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA2-CA3) in the sulfite group compared with the control group (p < 0.05, Mann Whitney U test). It was concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA2-CA3 subdivisions of the rat hippocampus.

The effect of sodium metabisulfite on visual evoked potentials in rats with hypercholesterolemia.

This study aimed to investigate the effects of hypercholesterolemia on visual evoked potentials (VEPs) and sulfite additional effects. Rats were assigned as follows: control (C), sulfite (S), hypercholesterolemia (H), vitamin E (E), sulfite + vitamin E (SE), hypercholesterolemia + sulfite (HS), hypercholesterolemia + vitamin E (HE), and hypercholesterolemia + sulfite + vitamin E (HSE). Hypercholesterolemic diet led significant increase in plasma cholesterol levels of rats. Brain thiobarbituric acid reactive substances (TBARS) levels were significantly increased in S, E, SE, HE and HSE groups compared with C. TBARS levels were increased in HE and HSE groups as compared to HS group. Nitrite levels were decreased in S, SE, H, HS and HSE groups compared with C. Nitrite level was notably increased in the HE group compared with H group. Sulfite exposure prolonged N1 and P3 latencies of VEP in group S compared with C. Prolonged VEP latencies by sulfite were significantly decreased by vitamin E in SE group. Cholesterol rich diet increased VEP latencies in comparison with control latencies. Sulfite gave rise to an additional increase in P3 latency in HS group compared with H group. Vitamin E-treated animals had notably shortened latencies of VEP components in HE and HSE groups according to the H and HS groups, respectively.

Ileal interposition improves metabolic syndrome parameters in a rat model of metabolic syndrome induced by monosodium glutamate.

AIMS: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities. Anatomically restructuring of the gastrointestinal system has recently been an important subject of research in the treatment of MetS and closely related diseases. The aim of this study is to ensure the remission of parameters that define MetS by ileal interposition (IT) and to examine the effect of IT on plasma total GLP-1 and pancreatic GLP-1R expression. MAIN METHODS: To induce MetS, newborn male Wistar albino rats were given MSG (4 g/mg) on days 0, 2, 4, 6, 8, and 10. The control group was injected with saline. In the 5th month, IT or sham surgery was performed on the MetS rats. The lipid levels, abdominal obesity, insulin level, OGTT, Lee index, HOMA-IR, plasma GLP-1 and pancreas GLP-1R expression were evaluated 2 months after surgery. KEY FINDINGS: The results showed that IT significantly improved hyperinsulinemia (p = 0.013) and lipid profile (TG p = 0.0001; TCHOL p = 0.018; HDL p = 0.001). Furthermore, it normalized the Lee index (p = 0.006) and insulin resistance. The IT did not affect the secretion of the GLP-1, but the expression levels of pancreas GLP-1R were increased (p = 0.006). SIGNIFICANCE: IT surgery corrected the MetS parameters in this rat model. The healing effects of IT surgery could be caused by mechanisms in the target tissues of insulin. The decrease in pancreatic GLP-1R levels in the MetS groups might be a compensatory response to the harmful effects of hyperinsulinemia in these groups. These results show that IT can be useful in the treatment of MetS.

Effect of sulfite on antioxidant enzymes and lipid peroxidation in normal and sulfite oxidase-deficient rat erythrocytes.

Sulfite and related chemical such as sulfite salts and sulfur dioxide has been used as a preservative in food and drugs. This molecule has also been generated from the catabolism of sulfur-containing amino acids. Sulfite is a very reactive and potentially toxic molecule and has to be detoxified by the enzyme sulfite oxidase (SOX). The aim of this study was to investigate the effects of ingested sulfite on erythrocyte antioxidant status by measuring glucose-6-phosphate dehydrogenase (G-6-PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant status by measuring thiobarbituric acid reactive substances (TBARS) in normal and SOX-deficient rats. Rats were assigned to four groups (n = 10 rats/group) as follows; control (C), sulfite (CS), deficient (D), and deficient + sulfite (DS). SOX deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten (W). Sulfite (25 mg/kg) was administered to the animals via their drinking water. At the end of 6 weeks, Erythrocyte G-6-PD, SOD, and GPx but not CAT activities were found to be significantly increased with and without sulfite treatment in SOX-deficient groups. Sulfite treatment alone was also significantly increased erythrocytes' SOD activity in CS group compared to control. TBARS levels were found to be significantly increased in CS and DS groups and decreased in D group. When SOX-deficient rats treated with sulfite, TBARS level was still higher than other groups. In conclusion, these results suggested that erythrocyte antioxidant capacity, a defense mechanism against the oxidative challenge, increased by endogenous and exogenous sulfite due to its oxidant nature. This increase was also observed in CS and DS groups but it was insufficient to prevent lipid peroxidation.