ABSTRACT
Gentamicin is commonly used against gram-negative microorganisms. Its therapeutic use is mainly limited by nephrotoxicity. This study was aimed at evaluating the effect of rutin on oxidative stress, inflammation, apoptosis, and autophagy in gentamicin-induced nephrotoxicity in rats. The rats were treated with saline intraperitoneally (group I), 150 mg/kg of rutin orally (group II), 80 mg/kg of gentamicin intraperitoneally for 8 d (group III), or 150 mg/kg of rutin plus 80 mg/kg of gentamicin (group IV). The serum urea, creatinine, kidney malondialdehyde (MDA), and reduced glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and protein concentration were measured, and renal histopathology analysis and immunohistochemical staining were performed. Rutin pretreatment attenuated nephrotoxicity induced by gentamicin by reducing the urea, creatinine, and MDA levels and increasing the SOD, CAT, and GPx activity, and the GSH levels. The rutin also inhibited inducible nitric oxide synthase (iNOS), cleaved caspase-3 and light chain 3B (LC3B), as evidenced by immunohistochemical staining. The present study demonstrates that rutin exhibits antioxidant, anti-inflammatory, anti-apoptotic, and anti-autophagic effects and that it attenuates gentamicin-induced nephrotoxicity in rats.
Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Gentamicins/adverse effects , Inflammation , Kidney Diseases , Oxidative Stress/drug effects , Rutin/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Disease Models, Animal , Glutathione Peroxidase/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Kidney/pathology , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , Kidney Diseases/metabolism , Kidney Diseases/physiopathology , Kidney Function Tests , Malondialdehyde/metabolism , Nitric Oxide Synthase Type II/metabolism , Protective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolismABSTRACT
A simple high-performance liquid chromatographic (HPLC) method was developed for the analysis of atorvastatin (AT) and its impurities in bulk drug and tablets. This method has shown good resolution for AT, desfluoro-atorvastatin (DFAT), diastereomer-atorvastatin (DSAT), unknown impurities and formulation excipients of tablets. A gradient reverse-phase HPLC assay was used with UV detection. Some solvent systems prepared using methanol or acetonitrile and water or buffer systems with different pH values were tested. Capacity factors of related substances were calculated at all tested systems. Best resolution has been determined using a Luna C18 column with acetonitrile-ammonium acetate buffer pH 4-tetrahydrofuran (THF) as mobile phase. Samples were eluted gradiently with the mobile phase at flowrate 1.0 ml min(-1) and detected at 248 nm. The proposed method was applied to the determination of impurities and were found to contain 0.057-0.081, 0.072-0.097, 0.608-0.664% of the DFAT, DSAT and total impurity, respectively.
Subject(s)
Drug Contamination , Heptanoic Acids/analysis , Heptanoic Acids/standards , Pyrroles/analysis , Pyrroles/standards , Atorvastatin , Chromatography, High Pressure Liquid/methods , Heptanoic Acids/chemistry , Pyrroles/chemistry , TabletsABSTRACT
An accurate and precise spectrofluorimetric method is presented for the determination of lisinopril based on the formation of a derivative formed with 7-chloro-4-nitrobenzofurazan. The derivatization reaction proceeds quantitatively at pH 8.5-9.0 and 60 degrees C in 70 min when the molar ratio of reagent to the drug is 170. After the extraction with ethyl acetate the fluorescence intensity of the derivative was measured at 528 nm with excitation at 465 nm. Calibration graph is rectilinear over the range of 50-1000 ng/ml with detection and determination limits of 20 and 50 ng/ml, respectively. The regression equation is I(f) = 0.198C-0.299 (r = 0.9999). The method was applied to the commercially available tablets and the results were statistically compared with those obtained by official HPLC method.
