Hypolipidemic and Antioxidant Properties of Oryzanol Concentrate in Reducing Diabetic Nephropathy via SREBP1 Downregulation Rather than ß-Oxidation.

SCOPE: Diabetic nephropathy (DN) is a micro-vascular complication of chronic diabetes. Sterol regulatory element binding protein1 (SREBP1) participation in the development of DN is reported. Oryzanol concentrate (OC) at 0.1% and 0.3% is tested for its antioxidant and hypolipidemic effects. The aim of the work is to study the involvement of OC in the amelioration of DN in STZ-induced diabetic animal model. METHODS AND RESULTS: Animals were grouped into starch, high-fat, and OC-treated control/diabetic groups (SFC/SFD, HFC/HFD, OFC/OFD). The markers of DN, increased glomerular filtration rate and kidney weight, were evident in HFD and reduced in OFD group by ≈1.09 and ≈1.3 fold, respectively. The amelioration of defensive antioxidant enzyme activities and lipid peroxidation, expressions of lipid-associated biomolecules (SREBP1 and FAS) were also observed. HFD showed increased ECM accumulation of glycoproteins, particularly Type IV collagen, fibronectin. SREBP1-associated gene transforming growth factor-ß (TGF-ß) was reduced on treatment (OFD ≈ 1.3 fold) as to HFD (≈2.7 fold). CONCLUSION: Oryzanol concentrate, having hypolipidemic and antioxidant properties, also downregulated the lipid biosynthesis through reduced SREBP1-TGF-ß interactions (EMSA) and could effectively ameliorate DN. Gene (ACC2, Cpt1, and ACOX) expression studies showed that ß-oxidation was not involved in reducing DN.

Multi-spectroscopic characterization of bovine serum albumin upon interaction with atomoxetine / 药物分析学报

The quenching interaction of atomoxetine (ATX) with bovine serum albumin (BSA) was studied in vitro under optimal physiological condition (pH=7.4) by multi-spectroscopic techniques. The mechanism of ATX-BSA system was a dynamic quenching process and was confirmed by the fluorescence spectra and lifetime measurements. The number of binding sites, binding constants and other binding characteristics were computed. Thermodynamic parameters ΔH0 and ΔS0 indicated that intermolecular hydrophobic forces predominantly stabilized the drug-protein system. The average binding distance between BSA and ATX was studied by F?rsters theory. UV-absorption, Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD), synchronous spectra and three-dimensional (3D) fluorescence spectral results revealed the changes in micro-environment of secondary structure of protein upon the interaction with ATX. Displacement of site probes and the effects of some common metal ions on the binding of ATX with BSA interaction were also studied.

Fabrication of multiwalled carbon nanotube-surfactant modified sensor for the direct determination of toxic drug 4-aminoantipyrine☆ / 药物分析学报

A multi-walled carbon nanotube (MWCNT)-cetyltrimethylammonium bromide (CTAB) surfactant composite modified glassy carbon electrode (GCE) was developed as a novel system for the determination of 4-aminoantipyrine(AAP). The oxidation process was irreversible over the pH range studied and exhibited a diffusion controlled behavior. All experimental parameters were optimized. The combination of MWCNT-CTAB endows the biosensor with large surface area, good biological compatibility, electricity and stability, high selectivity and sensitivity. MWCNT-CTAB /GCE electrode gave a linear response for AAP from 5.0 × 10-9 to 4.0 × 10-8 M with a detection limit of 1.63 × 10-10 M. The modified electrode showed good selectivity against interfering species and also exhibited good reproducibility. The present electrochemical sensor based on the MWCNT-CTAB/GCE electrode was applied to the determination of AAP in real samples.

Multi-spectroscopic investigation of the binding interaction of fosfomycin with bovine serum albumin☆ / 药物分析学报

The interaction between fosfomycin (FOS) and bovine serum albumin (BSA) has been investigated effectively by multi-spectroscopic techniques under physiological pH 7.4. FOS quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites n and observed binding constant KA were measured by the fluorescence quenching method. The thermodynamic parameters △G0, △H0 and △S0 were calculated at different temperatures according to the van't Hoff equation. The site of binding of FOS in the protein was proposed to be Sudlow's site I based on displacement experiments using site markers viz. warfarin, ibuprofen and digitoxin. The distance r between the donor (BSA) and acceptor (FOS) molecules was obtained according to the F?rster theory. The effect of FOS on the conformation of BSA was analyzed using synchronous fluorescence spectra (SFS), circular dichroism (CD) and 3D fluorescence spectra. A molecular modeling study further confirmed the binding mode obtained by the experimental studies.

Non-covalent binding analysis of sulfamethoxazole to human serum albumin：Fluorescence spectroscopy, UV-vis, FT-IR, voltammetric and molecular modeling / 药物分析学报

This study was designed to examine the interaction of sulfamethoxazole (SMZ) with human serum albumin(HSA). Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of human serum albumin by SMZ was static mechanism. The binding constant values for the SMZ–HSA system were obtained to be 22,500 L/mol at 288 K, 15,600 L/mol at 298 K, and 8500 L/mol at 308 K. The distance r between donor and acceptor was evaluated according to the theory of F?ster energy transfer. The results of spectroscopic analysis and molecular modeling techniques showed that the conformation of human serum albumin had been changed in the presence of SMZ. The thermodynamic parameters, namely enthalpy change (ΔH0) -36.0 kJ/mol, entropy change (ΔS0) -41.3 J/mol K and free energy change (ΔG0) -23.7 kJ/mol, were calculated by using van’t Hoff equation. The effect of common ions on the binding of SMZ to HSA was tested.