ABSTRACT
We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. To determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats.
Subject(s)
Acute Kidney Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Gentamicins , Organic Anion Transport Protein 1/metabolism , Organic Anion Transporters, Sodium-Independent/metabolism , Peptides, Cyclic/therapeutic use , Protein Synthesis Inhibitors , Acute Kidney Injury/chemically induced , Angiotensin-Converting Enzyme Inhibitors/urine , Animals , Area Under Curve , Blotting, Western , Fluorescent Antibody Technique , Glomerular Filtration Rate/drug effects , Kidney Cortex/metabolism , Lipid Peroxidation/drug effects , Lisinopril/urine , Male , Malondialdehyde/metabolism , Mass Spectrometry , Organic Anion Transport Protein 1/biosynthesis , Organic Anion Transporters, Sodium-Independent/biosynthesis , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain ReactionABSTRACT
A simple, sensitive, and rapid chemiluminescence method combined with flow-injection analysis was developed for the determination of lisinopril. It was found that the chemiluminescence (CL) signal arising from the reaction of alkaline luminol with KMnO(4) could be significantly increased by addition of lisinopril in the presence of silver nanoparticles. The experimental parameters affecting the chemiluminescence reaction were carefully studied and the chemiluminescence reaction mechanism was briefly discussed. Under the selected conditions, the chemiluminescence intensity was proportional to the concentration of lisinopril ranging from 0.1 mg/L to 20.0 mg/L. The detection limit was 0.027 mg/L lisinopril and the relative standard deviation for 4.0 mg/L lisinopril solution was 1.9% over eleven repeated measurements. The proposed method was applied to the determination of lisinopril in tablets and spiked human urine samples.
Subject(s)
Lisinopril/analysis , Luminescent Measurements/methods , Luminol/chemistry , Metal Nanoparticles/chemistry , Potassium Permanganate/chemistry , Silver/chemistry , Flow Injection Analysis/methods , Humans , Lisinopril/chemistry , Lisinopril/urine , Microscopy, Electron, Transmission , Sensitivity and Specificity , Tablets/chemistryABSTRACT
A selective, sensitive and precise HPLC method with fluorimetric detection has been developed for the assay of lisinopril in human plasma and urine. The clean up of the sample was carried out by solid-phase extraction, firstly with C18-cartridge and secondly with a silica-cartridge. After a pre-column derivatization with fluorescamine, the reaction mixture was chromatographed on C18-column with gradient elution, using methanol and 0.02 M phosphate buffer (pH=3.2). The fluorescamine-lisinopril derivative was detected fluorimetrically by monitoring the emission at 477 nm, with excitation at 383 nm. Linear quantitative response curve was generated over a concentration range of 5-200 ng/ml and 25-1000 ng/ml for plasma and urine samples, respectively. The mean recovery of lisinopril from plasma and urine was 63.41 and 74.08%, respectively. Intra-day and inter-day R.S.D. and R.M.E. values at three different concentrations were assessed. The method was applied for pharmacokinetic study in a healthy volunteer after a single oral dose of 20 mg of the drug.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Lisinopril/pharmacokinetics , Spectrometry, Fluorescence/methods , Angiotensin-Converting Enzyme Inhibitors/blood , Angiotensin-Converting Enzyme Inhibitors/urine , Humans , Lisinopril/blood , Lisinopril/urine , Reproducibility of ResultsABSTRACT
A simple, accurate and precise high-performance liquid chromatographic method is described for assaying lisinopril in human urine. Urine (1 ml) containing lisinopril and enalaprilat (internal standard) was acidified with 10 microliters of 6 M nitric acid, passed through a Sep-Pak C18 cartridge and eluted with 3 ml of 10% acetonitrile, followed by 6 ml of distilled water. the separations were carried out using a mu Bondapak c18 column with a mobile phase comprising acetonitrile (60 ml), methanol (10 ml) and tetrahydrofuran (10 ml) in 15 mM phosphate buffer (920 ml) at pH 2.90. Separations were performed at 40 degrees C and detection was at 206 nm. Standard calibration plots of lisinopril in urine were linear (r > 0.998) and recovery was greater than 64%. The lowest quantifiable concentration was 0.5 micrograms/ml. Within-day and between-day imprecision (coefficient of variation) ranged from 2.51% to 9.26%, and inaccuracy was less than 8.3%.
