Effect of green tea extract on cyclosporine-induced nephrotoxicity in rats

Cyclosporine A [CsA] is a potent and effective immunosuppressive agent but its action is frequently accompanied by severe renal toxicity. The present study was designed to investigate the possible protective effect of green tea extract [GTE] on CsA-induced nephrotoxicity in rats. Animals were assigned into three groups as follows: I: CsA group, given CsA [50 mg/Kg body weight per day, subcutaneously] for 10 days: II: CsA + GTE group, supplemented with 100 mg/Kg body weight GTE as a daily oral dose three days before and concurrently with CsA treatment and III: control group, received the vehicle [olive oil, in the appropriate volume, subcutaneously]. Administration of GTE significantly ameliorated the renal tubular injury caused by CsA as evidenced by decreased urinary enzymes leakage [N-acetvyl-beta-D-glucosaminidase [NAG]. lactate dehydrogenase [LDH] and y-glutamy1 transferase [y-GT] as well as urinary glucose excretion. The deranged renal function was manifested by a significant increase in serum urea and craetinine levels, however, serum sodium and potassium levels were not significantly affected. GET succeeded in improvement of renal dysfunction by normalizing serum urea and creatinie levels. The renal oxidative stress was significantly reduced by GTE administration as evidenced by decreased malondialdehyde [MDA] level as well as enhancement of the antioxidant enzymes glutathione reductase [GR] and gIutathione- S-transferase [GST], however, to significant change in the increased renal gIutathione [GSH] content was observed. The protective effect of GTE was also evidenced by lowering the increased serum and renal nitrte/ nitrate [NOx] levels together with decreasing the elevated renal cytosolic calcium. These findings clearly indicate the protective potential of GTE against CsA-induced nephrotoxicity and suggest a significant contribution of its antioxidant activity to this beneficial effect

Biochemical effects of chronic abuse of ergogenic aids in rats

To investigate the potential health risks associated with recommended or overdoses of amino acids mixture such as Power Mix [PM], Branched Chain Amino Acids [BCAAs] or Ceratine [Cr] supplementation as ergogenic aids for short or long-term rats. Male Sprague Dawley rats were assigned into two major groups; the first group was orally treated with the above mentioned supplements for six weeks [short-term], and the second group was treated similarly but for twelve weeks [long-term]. Each of the short- and long-term group was subdivided into seven subgroups which were treated as follows: PM [0.8 g/kg/day], PM [2.4 g/kg/day], BCAAs [0.2 g/kg/day]. BCAAs 0.6 g/kg/day], Cr [2 g/kg/day], Cr [6 g/kg/day] and controls [kept without treatment]. Plasma amino acids levels beside renal, thyroid, adrenal, and hepatic functions were estimated. Significant elevation in total amino acids concentration was found as result of feeding with the three dietary supplements. Results showed significant increase in serum creatinine level in rats ingested with these ergogenic aids except the low dose of PM given for short- or long-term. High doses of the three supplements given for both short- and long-term and low doses of BCAAs and Cr given for long-term caused significant elevation in serum uric acid level. Significant increase in serum NAG activity was observed among the three dietary supplements. Also, significant rise in serum AST and ALT activities was obtained after feeding the three dietary supplements except the low dose of PM given for short-term. Serum T3 level was significantly increased by feeding BCAAs or Cr in high doses for long-term. None of the three supplements exerted significant change in serum TSH and T4 levels. High doses of PM, BCAAs or Cr given for either short- or long-term caused significant increase in serum corticosterone and significant decrease in plasma ACTH levels. The three dietary supplements resulted in significant increase in cytosolic AST and ALT activities except the low dose of PM given for short- and long-term as well as low dose of BCAAs and Cr given for short-term. The three dietary supplement except low dose of PM fed for short-term, caused significant rise in mitochondrial AST activity. This study showed that supplementation of high-dose of PM, BCAAs or Cr given for long-term as ergogenic aids induced renal and hepatic damage as well hormonal disturbances

Synthesis and in-vitro cytotoxic activity of novel benzo[b]phenazine-6,ll-Dione and 1,4-Naphthoquinone derivatives

5, 12 - Dihydrobenzophenazine-6, 11-diones, 2-Arylamino-3-chloro-l, 4-naphthoquinones and 6, ll-dihydrobenzo[b]phenazine-6, 11-diones, were synthesized from 2, 3-dichloro-l, 4-naphthoquinone and arylamines/ phenylenediamines. Studying the cytotoxicity using EAC and human cell lines revealed that 5, 12-dihydrobemo[b]phenazine-6, ll-dione [3] and 3-chloro-2-[2- pyridylamino]-l, 4-naphthoquinone [10] showed selective cytotoxicity against the human lung carcinoma cell line [H460] superior to doxorubicin. Compound 3 [16.25 uM] was 1.3 times higher than that of doxoruhicin. However, 1C50 value of compound 10 was 9.90 uM which was 2 times higher than that [20.10 uM] of doxorubicin. These compounds were inactive against liver carcinoma [HEPG2], brain tumor [U251], cervix carcinoma [HELA] and breast carcinoma [MCF7] cell lines

Molecular characterization of hair cuticle and its extracted proteins in seven mammalian species

Hair is an of the epidermis in mammals and consists of two large groups of human hair proteins. One is hard -keratins and the other is matrix proteins. The present investigation aimed to compare the ultrastructural of the hair scale using the scanning electron microscope, and the proteins and amino acids content of the keratin in seven mammalian species. The values of the hair thickness, x/y feret and hair pattern of the species in the present study confirm the presence of species-specific characteristics and ultra structural variation. The situation in man differs from the wild mammals due to damage of hair cuticle caused by mechanical abuse, exposure to ultraviolet radiation and chemical over processing. The maximum amount of extracted proteins from hair keratin was analyzed by SDS-PAGE. The electrophoretic patterns showed an overall degree of similarity. However, differences exist between species in the intensity of stain. Quantitatively, the electrophoretic patterns scanned and analyzed using gel protein analyzer. The results showed no difference between the molecular mass of some species, but different in molecular mass distribution. Amino acid composition of keratin of mammalian hair species of the present study showed some variation, especially for methionine, isoleucine, lysine and arginine. The other amino acids studied are significantly present in most hair. One of the later amino acid is cysteine. Cysteine is a very important due to the presence of disulfate cross-links

Spectrophotometric determination of pantoprazole sodium in presence of its degradation products

Four spectrophotometric procedures [A-D] for the determination of pantoprazole sodium were investigated. Procedures A and B are stability-indicating methods to determine the intact drug in presence of its degradation products; sulfenamide and sulfenic acid prepared by degrading the pure drug in borate buffer [pH 8] at 37C for 5 days. Procedure A is based on first derivative spectrophotometric measurement in ethanol at 305 nm, whilst procedure B involves coupling of the drug with 2,6-dichloroquinone chlorimide in ethanoldimethylformamide mixture to yield a purple coloured product picked at 515 nm. Procedures C and D depend on charge transfer complexation with dichlorophenol indophenol and dichloronaphthoquinone in CHCl3-methanol and dimethylformamide yielding blue and orange radical anions with lambda max at 640 and 495 nm, respectively. Regression analysis of Beer's plots show good correlations [r=0.9992- 0.9999] and the calibration curves are linear over the ranges of 5-20 mug ml-1, 30-240 mug ml-1, 2-16 mug ml-1 and 40-320 mug ml-1 for procedures A,B,C and D, respectively. The detection limits range between 0.14 and 4.16 mug ml-1. Procedures A and B retain their accuracies in presence of up to 60% and 30% of pantoprazole degradation products, respectively. The average recoveries for commercial tablets are 98.9-100.4%. The results proved to be reproducible and in accordance with those given by a compendial method[11]

Cyanoethylation and mannich reactions with 4-aroyl-6-phenylpyridazin-3 [2H] -ones

As a part of our recent studies on pyridazinyl ketones[1-3], 4-aroyl-6-phenylpyridazin -3[2H]- ones were recently prepared in this laboratory by a new general and convenient method [1]. We would like to report, in this part, some reactions of these aroyl pyridazinones. When 4- aroyl -6-phenylpyridazin-3[2H]-ones [la-c] were allowed to react with acrylonitrile in ethanol containing catalytic amounts of aqueous sodium hydroxide, they underwent a Michael- type addition to the activated double bond yielding 4-aroyl-2[2'-cyanoethyl]-6-phenylpyridazin-3[2H]-ones[2a-c], respectively

New synthesis and reactions of 4-benzoylphthalazin-1 [2H] -one

As a part of a programme directed towards the synthesis of aroyl pyridazines which are precursors of some fused pyridazine derivatives, Ismail et al.[1,2] reported recently a novel method for the synthesis of 4-aroylpyridazin-3[2H] ones [3]. This investigation deals with applying this method to the synthesis of 4-benzoylphthalazin-l [2H]-one [1] which was first prepared in poor yield as a product of the rearrangement of 4-benzoylphthalazine[4] Now we would like to report a simple convenient method for the synthesis of 4-benzoyl-phthalazin -1 [2H]-one [1] which involves the oxidation of 4-benzylphthalazin-l[2H]-one [2] by sodium dichromate in acetic acid

Synthesis of some pyridazinyl acid derivatives

In a previous report we studied the thione-thiol tautomerism in 6-arylpyridazin-3 [2H]-thiones and came to the conclusion that these compounds exist mainly, if not entirely in the thione form. However the reacting tautomer of these compounds was found to depend upon the reaction medium. In continuation to this study, this report deals with the reaction of 6-arylpyridazin-3 [2H]-thiones with ethyl bromoacetate and acrylonitrile as a simple route for the synthesis of some pyridazinyl acid derivatives of expected biological activity

Mannich reaction and cyanoethylation of some 6 [-styryl] pyridazinone derivatives

Many pyridazine derivatives are known to have marked biological effect being fungicides, herbicides, and central nerve depressants. Recently, 4-styrylpyridazines were found to inhibit choline acetyltransferase in vitro. The present investigation deals with the synthesis of some 2-substituted 6[infinity-styryl] pyridazinones. When 4, 5-dihydro-6 [alpha-styryl] pyridazin-3 [2H]-ones [1 a and b] were allowed to react with acrylonitrile they underwent cyanoethylation to give fairly good yields of 2- [2'-cyanoethyl]*4,5-dihydro-6 [infinity-styryl] pryidaœin-3 [2H]-ones [3 a and b], respectively. The structure of 3 was confirmed by : [i] Microanalytical data [II] their infrared spectra lack the NH stretching frequencies while they show strong absorptions characteristic of vco and vC=N [Table 1]. These spectral features exclude the possibility of attack at C[4] leading to the formation of [2], [iii] the alkaline hydrolysis of these compounds gave the corresponding acids namely 2-[2-carboxyethyl]-4,5-dihydro-6 [infinity styryl]pyridazin-3 [2H]-ones [4a and b] whose infrared spectra lack the C=N stretching frequencies while they show the carbonyl stretching frequencies of both pyridazinone system and carboxylic acids in addition to broad absorptions in the 3 micro region characteristic of the polymeric hydroxyl groups of carboxylic acids

Reaction of o-acylaminobenzazides with amines and hydrazines

Azides in general and 0-acylaminobenzazides 1, in particular, are unstable compounds that decompose easily. The decomposition product of 1 is dependent upon the medium of reaction. Decomposition in boiling benzene gives the urea derivative 2, while decomposition in hot acetic acid medium gives the benzimidazolone derivative 3. Both of latter compounds are formed via the formation of the isocyanate derivative 4, the primary decomposition product of the azide. The urea derivative 2 was reported to be formed by the reaction of the isocyanate derivative 4 with the amine formed when part of 4 was hydrolysed under the influence of moisture present in the reaction medium