Aluminum-induced molecular neurodegeneration: The protective role of genistein and chickpea extract.

Neurotoxicity of Al is well established and linked to oxidative damage and neurodegeneration. This study investigated the protective role of genistein (Gen) and chickpea extract (CPE) against AlCl3-induced neurodegeneration. HPLC analysis revealed that biochanin A-7-O-ß-D-glucoside and biochanin A are the major components of the CPE. Gene expression of TNF-α, APP, BACE1, PSEN-2 and ER-ß were assessed in brain extract using RT-PCR. Also, NF-кB subunit P65 and COX-2 expression were evaluated by western blotting. The cholinergic function, histological examination and oxidative status were also estimated. The AlCl3 significantly up regulated the expression of the NF-кB subunit P65, COX-2, TNF- α, BACE1and APP while it significantly down regulated PSEN-2 and ER-ß expression. The activity of acetyl cholinesterase (AChE) and the oxidative stress parameters as well as the histological examination confirmed the deleterious effect of AlCl3. The administration of either CPE or Gen attenuated the expression of inflammatory cytokines, inhibited the amyloidogenesis and restored both the AChE activity and ER-ß expression. Gen and CPE also inhibited the oxidative stress and ameliorated the histological alterations. Accordingly, the present study provides an insight on the molecular role of Gen and CPE as protective agents against neuronal injury.

Changes in Oxidative Stress and Antioxidant Enzyme Activities in Streptozotocin-Induced Diabetes Mellitus in Rats: Role of Alhagi maurorum Extracts.

Alhagi maurorum (camel thorn plant) is a promising medicinal plant due to the presence of flavonoids and phenolic compounds as major contents of its constituents. No previous study has been conducted before on A. maurorum extracts as an antioxidative stress and/or antidiabetic herb in STZ-induced DM in rats. Therefore, four groups of rats were allocated as control (C), STZ-induced DM (D), and STZ-induced DM supplemented with 300 mg/kg BW of either aqueous extract (WE) or ethanolic extract (EE) of A. maurorum. The plasma levels of glucose, TG, TC, LDL-C and VLDL-C, MDA, and bilirubin and the activities of transaminases and GR were significantly increased in the diabetic group. Also, diabetic rats showed severe glucose intolerance and histopathological changes in their livers. In addition, levels of insulin, total proteins, GSH, and HDL-C and the activities of SOD, GPx, and GST were significantly decreased in the diabetic rats compared to those of the control group. The ingestion of A. maurorum extracts lowered the blood glucose levels during the OGTT compared to the diabetic rats and restored all tested parameters to their normal levels with the exception of insulin level that could not be restored. It is concluded that A. maurorum extracts decreased elevated blood glucose levels and hyperlipidemia and suppressed oxidative stress caused by diabetes mellitus in rats.

Oxidative damage, hyperlipidemia and histological alterations of cardiac and skeletal muscles induced by different doses of diazinon in female rats.

Diazinon (Dz) is used in ectoparasiticide formulations for external parasitic control, resulting in environmental deleterious effects on biological systems. Thus we aimed to investigate the effects of different doses of diazinon on some biochemical parameters and histological alterations in female rats. The rats were divided into two groups. The first group was used as control. The second group was divided into four subgroups that were treated with 8, 10, 12 and 20 mg/kg BW of diazinon, respectively. The results showed that treatment with Dz induced significant (p<0.05) increases in the level of serum malondialdehyde (MDA) and the activity of lactate dehydrogenase (LDH). The results revealed significant (p<0.05) decreases in the activities of serum acetylcholinesterase (AChE), glutathione peroxidase (GPx) and superoxide dismutase (SOD). Meanwhile, the results showed significant (p<0.05) increases in serum total lipids, total cholesterol, triglycerides, high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C) in Dz-treated subgroups, compared to the control group. The histological analysis of cardiac and skeletal muscle fibers demonstrated large areas of degenerating muscle fibers with evident loss of transverse striations and wide interfascicular spaces. In conclusion, Dz induced varying degrees of oxidative damage and histological alterations according to its dose.

Analysis of fludrocortisone acetate and its solid dosage forms by high-performance liquid chromatography.

A newly developed reversed-phase high-performance liquid chromatographic assay and test method for determining content uniformity are described for fludrocortisone acetate. The method is stability indicating and separates most known degradation products and impurities. In addition, the method is simple, sensitive, accurate, and relatively free of interferences. The coefficient of variation for multiple weight assays is between 0.3 and 1.8%.

Kinetics and mechanism of reaction of m-nitrobenzhydrazide and other hydrazines with acetic acid.

A comprehensive kinetic study was conducted of the reactions of m-nitrobenzhydrazide and some other hydrazines with acetic acid. The overall reaction rate for all of the compounds studied followed pseudo-first-order kinetics. The temperature dependence of the m-nitrobenzhydrazide degradation reaction was determined. The reaction rate dependence on the acetic acid concentration was found to be close to first order. High-pressure liquid chromatography was used extensively in identifying and measuring the appearance or disappearance rates of m-nitrobenzhydrazide degradation products in acetous solution. With m-nitrobenzhydrazide, the major degradation products were N,N'-bis(m-nitrobenzoyl)hydrazine, N-acetyl-N'-m-nitrobenzoylhydrazine, diacetylhydrazine, and hydrazine. The concentration profiles of these products in solution suggested a complex mechanism by which hydrazides react with acetic acid. All eight rate constants at 61 degrees in the suggested mechanism were calculated by an approximation method based on experimental data. The findings in the present study indicate that acetic acid is to be avoided as a solvent for hydrazine derivatives.

Semiautomated system for high-pressure liquid chromatographic determination of dissolution rate of fludrocortisone acetate tablets.

A new semiautomated high-pressure liquid chromatographic (HPLC) system is described to determine the dissolution rate of fludrocortisone acetate tablets. The system uses a miniaturized dissolution basket and shaft assembly having the same geometry as that given in USP XIX. This reduced size permits use of smaller volumes of dissolution medium, allowing most very low dose oral solid dosage forms to be handled. The USP dissolution kettle was also replaced with a new miniaturized vessel that continuously filters the sample solution before it enters the flow system. Volumes of dissolution medium as small as 15 ml can be accommodated, depending on the sensitivity of the assay employed and the solubility of the drug substance under study. The concentration of fludrocortisone acetate in solution was monitored by a new HPLC system employing a reversed-phase column compatible with the aqueous dissolution medium used. A comparative dissolution study of different lots was made using different basket rotation speeds.

Computerized automated system for determining dissolution rate profiles for solid dosage forms.

A unique automated system was developed for the measurement of dissolution rates of tablets and capsules. This system, which adheres to principles set forth in the compendia, can test six dosage forms simultaneously. It is modular in form and capable of maintaining sink conditions, and it can handle any type of chemistry amenable to an automatic analyzer. In addition to the usual dissolution apparatus, the system includes a 12-channel combination sampling and solvent addition pump, a sequence control module, pertinent automated analyzer components, a spectrophotometer or fluorometer, an optional recorder, a specially designed digitizing system, and a teletype equipped with a paper tape punch reader and acoustic coupler. Each dissolution flask is automatically sampled every 6 min. Standards may be run either before or after the samples. Since dissolution, sampling, chemistry, and readout are all accomplished simultaneously, the complete test time is essentially reduced to the dissolution time itself. At the completion of sample dissolution, raw dissolution profile data are on the punched paper tape ready for computer processing via a time-sharing system. Developed software provides for the printout of a complete test report in less than 15 min.