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.

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.

Swimming exercise restores damaging effects of fructose-enriched diet on the liver in rats.

Fructose-enriched diet (FED) is increasing worldwide. The study aims to investigate oxidative, histopathological, and immunohistochemical effects of fructose-enriched diet and swimming exercise on liver tissue in rats. Wistar rats were divided into 4 groups: Group I (Control), Group II (FED), Group III (FED+Exercise), and Group IV (Control+Exercise). MDA levels and enzyme activities of SOD and CAT were measured in liver tissue. Also, histopathological and immunohistochemical examinations (caspase-3, RANKL, TNF-α, and HSP-70) were performed on the liver tissue. MDA levels and SOD activities were found to be significantly higher in Group III compared to the other groups (p < 0.05). SOD activity was found to be lower in Group II compared to Group I (p = 0.035). CAT activities did not differ significantly between groups. While degeneration was noticed in Group II, normal tissue architecture was observed in other groups. Caspase-3, RANKL, and TNF-α expressions were higher in Group II than in the other groups, while HSP-70 expression was lower (p < 0.05). Fructose-enriched diet increases oxidative damage, degeneration, inflammation, and necrosis in the liver. In addition, a fructose-enriched diet is damaging to the liver by increasing the expressions of caspase 3, TNF-α, and RANKL and decreasing the expression of HSP-70. Swimming exercise largely restores these effects.

Verbascoside potentiates the effect of tyrosine kinase inhibitors on the induction of apoptosis and oxidative stress via the Abl-mediated MAPK signalling pathway in chronic myeloid leukaemia.

Verbascoside (Verb) may exhibit potential antitumour activities in leukaemia. The present study investigated the effect of Verb, in combination with imatinib (IM), dasatinib (Das), lipopolysaccharide (LPS) and TNF, on cell survival, Abl expression, apoptosis, oxidative stress and the MAPK pathway in chronic myeloid leukaemia (CML) cells. Cell viability was determined using the WST-8 assay in K562 and R-K562 cells treated with Verb and/or IM, Das, LPS and TNF. Apoptosis and DNA damage in CML cells was detected by caspase-3 and comet analysis. The protein levels of Abl (Phospho-Tyr412), and total/phosphorylated p38, JNK and ERK in CML cells were analysed using a Colorimetric Cell-Based Assay. Oxidative stress was examined using total antioxidant and oxidant status assays. Treatment with Verb and/or tyrosine kinase inhibitors (TKIs), LPS and TNF resulted in a significant decrease in the Tyr-412 phosphorylation of Abl in K562 and R-K562 cells. In addition, cotreatment with Verb and IM or Das additively induced apoptosis by activating caspase-3 levels in both cell lines. Activation of p38 and JNK can result in growth arrest and cell death, whereas ERK stimulation results in cell division and differentiation. The present study demonstrated that cotreatment with Verb and TKIs suppressed phosphorylated-ERK1/2, whereas the levels of phosphorylated-p-38 and phosphorylated-JNK were significantly elevated by Verb and/or IM, Das, LPS and TNF, thus suggesting that Abl and Src inhibition could be involved in the effects of Verb on MAPK signalling in R-K562 cells. Furthermore, Verb elevated reactive oxygen species levels additively with TKIs in both cell lines by increasing the oxidant capacity and decreasing the antioxidant capacity. In conclusion, anti-leukemic mechanisms of Verb may be mediated by Abl protein and regulation of its downstream p38-MAPK/JNK pathway, caspase-3 and oxidative stress in CML cells.

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.

Nephrolithiasis during the first 6 months of life in exclusively breastfed infants.

BACKGROUND: We investigated etiology and prognosis of infantile nephrolithiasis, including whether lithogenic and anti-lithogenic content of breast milk affects its formation. METHODS: Thirty infants with nephrolithiasis and 30 healthy infants exclusively breastfed for the first 6 months of life were included in this prospective cohort case-control study. At entry, age, sex, and timing of birth of patients and controls were recorded. All patients were diagnosed and followed up periodically using ultrasonography. All infants received oral vitamin D (400 units/day). Lithogenic (calcium, oxalate, uric acid, phosphate) and anti-lithogenic (citrate, magnesium) components of maternal milk, serum calcium, phosphate, magnesium, 25-hydroxy vitamin D and parathormone, as well as spot urine calcium, uric acid, cystine, oxalate, magnesium, citrate/creatinine ratio, and calcium/citrate ratio were compared. RESULTS: Mean follow-up period was 56.1 ± 6.8 months. There was no difference concerning lithogenic and anti-lithogenic content of breast milk. Serum calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D levels (49.1 ± 19 vs. 26.7 ± 4 ng/ml, p < 0.001) were significantly higher and parathormone level significantly lower in patients. Random urine calcium/creatinine and calcium/citrate ratios were significantly higher in patient group (0.63 ± 0.40 vs. 0.42 ± 0.10 and 0.62 ± 0.12 vs. 0.41 ± 0.25 mg/mg, respectively, p < 0.01). Three patients were lost to follow-up after the first year. At last follow-up, calculi disappeared in 25/27 remaining patients without interventions or therapy. CONCLUSIONS: Breast milk does not have an etiologic effect in infantile nephrolithiasis. Higher serum vitamin D levels may have roles in development of lower levels of PTH and higher levels of serum and urine calcium, leading to stone formation. The prognosis for infantile stones is excellent. Graphical abstract.

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.

Effect of MDR C3435T polymorphism on Varenicline treatment in quit smoking

Despite so many global efforts, smoking still remains to be one of the most common addictions worldwide. Even though most smokers wish to quit smoking, many of them fail. In this respect, genetic variants are thought to be remarkable factors in nicotine dependence and in treatment of smoking cessation. This is a paper investigating a single variant p-glycoprotein (P-gp) polymorphisms and its effect on Varenicline efficacy in the smoking cessation. 158 smokers and 52 non-smoker healthy volunteers were included. We determined the P-gp C3435T gene polymorphisms in all subjects. Face to face interviews with smokers were performed for smoking cessation and Varenicline was given for smoking cessation. Cessation success was evaluated in the 6th month and success rates were compared according to the P-gp genotype distributions. In our study, smoking cessation rate by Varenicline was 57.0%. This rate was 55.0% in females, and 57.2% in males (p=0.85). The P-gp C3435T gene distribution was similar in control, quitters and not-quitter groups. Cessation rate was at highest point in genotype CT (62.2%) and at the lowest in TT (47.6%). It was 53.8% in genotype CC and there was no statistically significant difference (p=0.27). Our results suggest that genetic variants of P-gp C3435T did not significantly affect Varenicline treatment for smoking cessation.