An investigation of acute effects at various doses of malathion on glucose homeostasis and insulin resistance in rat liver, pancreas and serum

Objective. This study investigates acute effects of various doses of Malathion on glucose homeostasis and insulin resistance in rat. Methods. Rats were randomly divided into four groups of 6 animals each. Corn oil was given orally to Group 1. Group 2, Group 3, and Group 4 received malathion dissolved in corn oil via oral administration at the doses of 100, 200 and 400 mg/kg, respectively. 24 hours later the rats were sacrificed. Results. Acute administration of Malathion led to a decrease in serum butryl cholinesterase (BChE) levels at all doses tested. It also caused a significant increase in serum advanced glycation end products (AGEs), insulin, and TNF-α levels at all doses. Moreover, Malathion administration raised the liver ALT, AST and LDH, TNF-α, and glycogen levels in a dose dependent manner. It also led to a remarkable increase in pancreatic insulin levels at all doses. Conclusions. Acute administrations of Malathion affect glucose homeostasis in a dose dependent manner through its effects on the liver, serum, and pancreas

Characterization and Differentiation of Adipose Tissue by Spectroscopic and Spectral Imaging Techniques

Adipose tissue is a metabolically active endocrine organ having a distribution in a variety of locations in whole body; therefore, it is crucial to understand the adipocyte metabolism in health and disease. Spectroscopic techniques such as Fourier transform infrared (FTIR), Raman, nuclear magnetic resonance (NMR) are widely used to characterize biological systems by monitoring cellular molecules such as lipids, carbohydrates, and proteins. Obesity or insulin resistance-induced molecular alterations in adipose tissue can be detected using these techniques. Spectral imaging of adipose tissue provides high-quality information involving molecular compositional, structural, and functional alterations for characterization and differentiation of adipocytes (brown, white) in different adipose tissue regions (visceral, subcutaneous, etc.). In this chapter, applications of spectroscopic and spectral imaging techniques for characterization and differentiation of various adipose tissues will be discussed, which will shed light to better understand adipose tissue metabolism and provide new insight into diagnosis and treatment of some metabolic diseases such as obesity

Applications of Infrared Spectroscopy and Microscopy in Diagnosis of Obesity

Infrared (IR) spectroscopy is a vibrational spectroscopic technique based on the absorption of infrared radiation by matters that excite vibrations of molecular bonds. It is a powerful method for investigating structural, functional, and compositional changes in biomolecules, cells, and tissues. In recent years, scientific researchers have continued to increase the performance of this technique on clinical cases such as cancers and metabolic disorders. Obesity is one of the main factors that increases the risk of many diseases and contributes to functional disabilities in tissues such as adipose, liver, and muscle. Applications of IR spectroscopic techniques allow identifying molecular changes due to obesity, to understand the molecular mechanism of the disease, to identify specific spectral biomarkers that can be used in diagnosis. In addition, these spectral biomarkers can be used to identify the appropriate drugs and their doses for treatment. In this chapter, applications of IR spectroscopic and microscopic techniques to the characterization and understanding the obesity metabolism will be presented. The discriminatory power of these techniques in diagnosis of obesity will be discussed. In future, these novel approaches will shed light on the internal diagnosis of obesity in clinical application

Evaluation of Oxidant-Antioxidant Status of Fluvoxamine on Human Lymphocyte Cell Culture

Depression is one of the prevalent psychiatric diseases in Turkey and the world. Fluvoxamine is a strong selective serotonin reuptake inhibitor (SSRI) that is used as an antidepressant. No study investigating the doses of Fluvoxamine treatment that may lead to a disruption in the oxidant-antioxidant balance on the cellular level in addition to its beneficial effects has been found in the literature. For this purpose, by creating Fluvoxamine application groups at the doses of 7.5, 15, 30 and 60 μM and durations of 24 and 48 hours on human lymphocyte cell cultures, we investigated the total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI). According to the results of the study, the TOS levels of all dose groups increased significantly in the 24- and 48-hour applications (p lt;0.05). While the TAS levels significantly increased in the 24-hour application of the doses of 7.5 and 15 μM and 48-application of the dose of 7.5 μM, they significantly decreased in the 24- and 48-hour applications of the doses of 30 and 60 μM (p lt;0.05). The OSI level increased significantly in the 24- and 48-hour applications of the doses of 30 and 60 μM. The results of our study demonstrated that, in the 24- and 48-hour applications of the doses of 30 and 60 μM, the antioxidant system could not compensate and the cells exposed to oxidative stress

Infrared spectroscopic studies on the dipalmitoyl phosphatidylcholine bilayer interactions with calcium phosphate: Effect of vitamin D 2

Abstract. In the present work, the interaction of calcium-phosphate with DPPC (dipalmitoyl phosphatidylcholine) model membranes has been studied in the presence and absence of vitamin D2 by using Fourier Transform Infrared (FTIR) spectroscopy. Calcium and phosphorus are the most abundant elements in the body. They combine in the form of calcium phosphate salt, called hydroxyapatite. Hydroxyapatite is the major structural component of the bone. Calcium phosphate assists with the digestion and absorption of food and is vitally important for the building of sturdy bone and body structures and a robust constitution. Phosphorus is extracted from foods and its use is controlled by vitamin D and calcium. FTIR spectral analysis results suggested that, calcium-phosphate complex, which is the major component of the bones, decreases the phase transition temperature to lower values, causes a loss in cooperativity of the acyl chains, decreases the order of the membrane in both phases and decreases the dynamics of the membrane in the liquid crystalline phase, increases the flexibility of the chains in the center of the bilayer in both phases, and increases the mobility of the head group of DPPC in the gel phase. The effect of calcium-phosphate on DPPC liposomes diminishes with the addition of vitamin D2 into the liposomes. Our results suggest how calcium-phosphate and/or vitamin D2, which have indispensable role for the functioning of the bone tissue, affect the thermal behaviour of DPPC liposomes at molecular level

FTIR studies of vitamin E-cholesterol-DPPC membrane interactions in CH2 region

Binary and ternary mixtures of α-tocopherol (αT), cholesterol and dipalmitoyl phosphatidylcholine (DPPC) in the form of multilamellar liposomes have been investigated by Fourier Transform Infrared Spectroscopy (FTIR). Investigation of frequencies, bandwidths and band shapes of CH2 stretching and scissoring bands indicate that the effect of αT is dominant in comparison with cholesterol and αT decreases the interaction of cholesterol with phospholipid membranes. © Springer-Verlag 1996

Kas özellikleri ve obezite arasındaki ilişkinin genetik ve biyofiziksel yöntemlerle araştırılması

TÜBİTAK SBAG Proje01.04.2012Obesity, which arises from changes in lifestyle and feeding habits in developed and developing countries, is becoming a threat for human health due to its increasing prevelance. Especially, the increase in the consumption of high fat diets is one of the main factors that take role in the generation of obesity. Clinical disorders, such as type 2 diabetes, dislipidemia, cardiovascular diseases and hypertension, are all basic metabolic diseases in close relation with obesity. These metabolic disorders generally trigger each others’ prevalence. The common property shared by obesity and these metabolic disorders is the inability of insulin to exert its action on tissues, even though insulin is produced by the body. Impaired insulin sensitivity in skeletal muscle tissue is one of the most common symptom in pathophysiology of diabetes and obesity. While insulin resistance have not been yet fully established for clarity, in recent studies, more and more evidence reveals that the distribution and types of lipids are the deterministic factors in generation of insulin resistance. Therefore, determination of the distribution and types of lipids accumulated in the skeletal muscle are necessary in order to explain the generation of insulin resistance mechanism in obesity. The aim of this study was to establish the structural and functional changes in longissimus dorsi (LD) and quadriceps (Q) skeletal muscle tissue macromolecules, especially lipid, and determination of the types and distribution of the lipids within these tissues in control (C57BL/6J and DBA/2J), Berlin muscle mouse inbred (BMMI) lines and Berlin fat mouse inbred (BFMI) lines and thus, to do the characterization of these skeletal muscle tissues of inbred mouse models. For this this purpose, attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy was used to determine the properties of macromolecules, FTIR microspectroscopy was used to monitor the distribution of these macromolecules especially lipids within the skeletal muscles, confocal microscopy technique was used to monitor the lipid content of muscle fibers and to determine fibers types that these lipids accumulated more intensely and high performance liquid chromatography (HPLC) technique was used to determine the types and amounts of lipids stored in these muscles. In this study, skeletal muscle tissues of the control (C57BL/6J and DBA/2J), BMMI mice which were fed with standard breeding diet (SBD) and BFMI mice which were fed with either SBD or high-fat diet (HFD) were investigated. 14 In this study, serum levels of glucose, triglyceride and non-esterified fatty acid were found to be increased in BMMI806 among the BMMI lines and BFMI860, BFMI861 within the BFMI lines and these lines showed a slower response to insulin injection than the other lines. These results were the indicators of the development of insulin resistance in these lines. BMMI806, BFMI860 and BFMI861 lines represented different properties in comparison to the other lines. ATR-FTIR spectroscopic results revealed that BMMI806, BFMI860 ve BFMI861 mice possess higher amount of triglyceride, cholesterol ester and saturated lipid content, lower amount of unsaturated lipid content, more methly groups in lipid structure and lipids with shorther hydrocarbon chain lenght in comparison to other groups. The lipid content in skeletal muscles of all BFMI mice fed with a HFD increased, except for BFMI852 line which did not respond to feeding with HFD in terms of lipid content. The highest lipid content was found to be in BFMI860 line among the groups fed with a HFD. It had been demonstrated that the skeletal muscles of BMMI806 line amoung BMMI lines, BFMI860 and BFMI861 lines within BFMI mice had the lowest olefinic band area and unsaturation index; therefore these lines are more prone to lipid peroxidation. Lipids extracted from LD an Q skeletal muscles of control, BFMI and BMMI lines of SBD and also BFMI lines of HFD were separated, characterized and quantified by HPLC-ELSD technique. In BFMI lines, lipids were detected in higher concentrations regarding to BMMI lines. Among BFMI lines, the highest lipid concentrations were seen in BFMI860 and BFMI861 lines, respectively. In BFMI lines, other than BFMI860 and BFMI861, the concentration of detected lipids were low. The effects of HFD on the concentration of lipids were obvious. In BFMI lines which fed with HFD, had more lipid content compared to BFMI mice which fed with SBD. These findings support the ATRFTIR spectroscopic results, which was performed on the same tissues of same lines. In LD and Q muscles BMMI826 and BMMI866 lines, which were characterized as myostatin mutants, were found to have less lipid content. In myostatin wild-type BMMI806 line, the lipid concentration was detected to be higher than the other BMMI lines. These findings are also in agreement with the ATR-FTIR spectroscopic results. Lipid amounts in LD and Q skeletal muscles were also determined and compared with each other. According to the results, lipid concentration was found to be higher in LD skeletal muscle when compared to the lipid concentration in Q muscle. Via imaging techniques, higher amount of neutral lipid accumulation was observed in the cross-sections of skeletal muscle type IIa and intermediate muscle fiber, which do 15 have more oxidative metabolism. In these muscle fibers where high lipid accumulation is present, high lipit/protein distribution, high amount of methylene (CH2) groups, low amount of methyl groups (CH3) in the lipid structure, high amount of triglyceride content (carboynl, C=O) and lipids with longer chain lenght were observed. Furthermore, it was also found that, these fibers display a higher unsaturation index and lower glycogen content. This lipid accumulation was found to be the highest in the skeletal muscles of BFMI860 mice when compared to other obese mouse lines. The effect of HFD on BFMI860 mouse line regarding to the lipid accumulation, was observed to be more dramatic. When all results obtained were evaluated, with their genetically complex background, BFMI860 and BMMI806 were determined to be the most suitable lines for the investigation of spontaneous obesity in humans among all BFMI and BMMI lines. Furthermore, according to the results of this study, in LD muscles which is responsible for the posture and include more type IIa fibers than Q muscle, represented more significant results

Engineering cooperative tecto–RNA complexes having programmable stoichiometries

High affinity and specificity RNA–RNA binding interfaces can be constructed by combining pairs of GNRA loop/loop–receptor interaction motifs. These interactions can be fused using flexible four-way junction motifs to create divalent, self-assembling scaffolding units (‘tecto-RNA’) that have favorable properties for nanomedicine and other applications. We describe the design and directed assembly of tecto-RNA units ranging from closed, cooperatively assembling ring-shaped complexes of programmable stoichiometries (dimers, trimers and tetramers) to open multimeric structures. The novelty of this work is that tuning of the stoichiometries of self-assembled complexes is achieved by precise positioning of the interaction motifs in the monomer units rather than changing their binding specificities. Structure-probing and transmission electron microscopy studies as well as thermodynamic analysis support formation of closed cooperative complexes that are highly resistant to nuclease digestion. The present designs provide two helical arms per RNA monomer for further functionalization aims