Phosphodiesterase type 5 inhibition attenuates cyclosporine A induced nephrotoxicity in mice.

We investigated the renal protective effects of phophodiesterase type 5 (PDE5) inhibitors in mice with cyclosporine A (CyA; a calcineurin phosphatase inhibitor) induced nephrotoxicity. Fifty male mice were divided into five groups of 10. Group 1 received no treatment, group 2 received only saline orally, group 3 received 30 mg/kg/day CyA by subcutaneous injection, group 4 received only 30 mg/kg/day vardenafil orally, and group 5 received 30 mg/kg/day CyA by subcutaneous injection and 30 mg/kg/day vardenafil orally. At 28 days, platelet-derived growth factor A (PDGF-A) and C (PDGF-C), transforming growth factor-beta 1 (TGF-ß1), cyclo-oxygenase 1 and 2 (COX-1 and COX-2), and P glycoprotein (Pgp) expression levels were measured in the renal tissues. In addition, expressions of COX-1 and COX-2 genes were determined using real-time PCR. PDE5 inhibitor administration ameliorated decreased PDGF-A and C, TGF-ß1, COX-1 and -2, and Pgp expression levels by modulation of cyclic guanosine monophosphate (cGMP) activity in kidneys. The relative expressions of COX-1 and COX-2 genes to GAPDH revealed that the maximum increase was obtained in the group treated with CyA and vardenafil for both COX-1 and COX-2 genes. Our study revealed that long term oral treatment with vardenafil protects kidneys from CyA induced nephrotoxicity. We showed that long term oral treatment with PDE5 prevents pathological kidney changes caused by CyA induced nephrotoxicity.

Investigation of liposome formulation effects on rivastigmine transport through human colonic adenocarcinoma cell line (CACO-2).

Transportations of rivastigmine containing liposomes across Caco-2 cells were studied and in vitro test results were compared with in vivo results. MTT test was used for cell viability studies. Series of formulations were prepared containing rivastigmine which is used for the treatment of Alzheimer's disease. Characterization and stability studies for liposome formulations were performed. Encapsulation efficiencies of liposomes were 35.4%, 25.2% and 29.9% for rivastigmine, rivastigmine-sodium taurocholate, rivastigmine-dimethyl-beta-CD liposomes, respectively. In stability studies, particle size and size distribution, zeta potential, rivastigmine amounts were determined and shelf lives of liposomes were calculated. Penetration properties of rivastigmine through Caco-2 cells, dialysis membrane and kinetics of release from liposomes were determined. Permeability coefficients were calculated after diffusion studies. The highest value of % cumulative amount of rivastigmine passed through caco-2 cell cultures was found to be 87.2% for rivastigmine-sodium taurocholate solution and 12.8% for rivastigmine-sodium taurocholate liposome. The highest permeability coefficient value was obtained with sodium taurocholate liposomes for -0.75. Rivastigmine liposomes and solutions were also applied to animals. Acetyl choline esterase (AChE) activity was determined by the Ellman method on mice. %AChE inhibition values were calculated using blood and brain tissue samples. The physical appearances of the brains were investigated by TEM microscope. The highest value of AChE inhibition was observed for rivastigmine and sodium taurocholate liposomes. The histological investigations and observations also supported these results.

Hydrated sodium calcium aluminosilicate for reduction of aflatoxin in quails (Coturnix coturnix japonica).

The purpose of the present study was to evaluate the toxic effects of aflatoxin (AF) on growth performance and various processing parameters of quails and to determine the preventive efficacy of hydrated sodium calcium aluminosilicate (HSCAS). One hundred and eighty 1-d-old quails of both sexes were randomly divided into 4 experimental groups with 5 replicates and 45 birds following weighing. The experimental design consisted of four dietary treatments: 1) control with 0 mg AF/kg of diet and 0% HSCAS; 2) 0.5% HSCAS; 3) 2.5 mg AF/kg of diet; 4) 2.5 mg AF/kg of diet plus 0.5% HSCAS. The chicks were housed in electrically heated battery cages and exposed to light for 24 h from hatching to 3 weeks of age. Quails consumed the diets and water ad libitum. Body weight (BW) was significantly (p < 0.001) increased by addition of HSCAS to AF diet. The lowest BW gains in groups received AF alone was observed at all periods. The reduction in BW gain caused by 2.5 mg AF/kg of diet was significantly (p < 0.001) diminished by the addition of 0.5% HSCAS to the diet. The addition of HSCAS to the AF diet significantly (p < 0.001) protected against decrease of feed intake at all periods with exception of the first period. None of the treatments altered significantly the feed conversion ratio (FCR). The relative weights of the liver, kidney and spleen were increased in the chickens consuming the AF alone diet. However, light microscopic examination demonstrated the addition of HSCAS to quail feed to partially decrease fat deposition caused by the toxin, and besides, electron microscopic examination of indicated a reorganization in the endoplasmic reticulum and increase in the number of ribosomes and polisomes. Furthermore, the decrease in the antibody titre induced by Newcastle vaccine, due to aflatoxins, was relatively prevented. No significant differences were observed for serum total protein, total cholesterol and glucose levels. The results of indicate that HSCAS is effective in preventing the deleterious effects of AF.

Light and electron microscopic studies on liver histology in chicks fed aflatoxin.

This study was carried out under both light and electron microscopy to investigate the effects on liver carbohydrate and lipid metabolism caused by aflatoxin (AF) fed to chicks. Twenty broiler chicks were used. The birds were housed in electrically heated battery cages and exposed to light for 24 h. Feed and water were provided ad libitum. The animals were allocated to two groups each made up of 10 broilers. Total aflatoxin levels of zero (0) and 5 mg of AF/kg feed (81.05% AFB1, 8.79% AFG1, 6.06% AFB2, and 4.10% AFG2) added to a commercial diet, were fed to chicks from hatching up to 3 weeks of age, when the experiment was terminated. The chicks were executed by cervical dislocation and liver samples were obtained for light and electron microscopy. Oil red 'O', Sudan Black B, periodic acid Schiff (PAS) and Best's carmine stains were used to reveal fat and glycogen in the liver. Histological changes in hepatocytes included increased lipid droplets, high glycogen content, and mild mononuclear cell infiltration in the portal areas. Ultrastructural findings were destruction of rough endoplasmic reticulum (rER), reduction in mitochondrial size, enlargement of bile canaliculi, and cisternal dilatation of the smooth endoplasmic reticulum (sER).

MYCOTOX and aflatoxicosis in quails.

1. This study was to evaluate the toxic effects of aflatoxin (AF) on growth performance of quail, and to determine the preventive efficacy of MYCOTOX (oxicinol, tymol, micronised yeast). 2. One hundred and eighty 1-d-old quail (Coturnix coturnix japonica) of both sexes were weighed and randomly divided into 4 experimental groups each with 5 replicates of 9 birds. 3. There were 4 dietary treatments: (1) control with 0 mg AF/kg diet and 0% MYCOTOX; (2) 0 mg AF/kg diet and 0.5% MYCOTOX; (3) 2.5 mg AF/kg diet and 0% MYCOTOX; (4) 2.5 mg AF/kg diet plus 0.5% MYCOTOX. The chicks were maintained on these treatments to 3 weeks of age. Quail consumed the diets and water ad libitum. 4. Body weight (BW) gains in groups receiving AF alone were the lowest at all periods. Feed intake was lowest in the group consuming the AF diet. The addition of MYCOTOX to the AF diet did not prevent or reduce the toxic effects of AF on feed intake at any time period. Feeding diets containing MYCOTOX alone did not change feed intake significantly. With the exception of the 1 to 7 d period, feed conversion of chicks fed the AF diet was similar to those of the other experimental groups. 5. Bursa of Fabricius weight decreased, whereas the relative weights of liver, kidney and spleen increased in quail consuming diets containing AF and AF plus MYCOTOX. Liver colour was normal in the control and MYCOTOX alone group, but was lighter in groups fed AF. 6. The results indicated that MYCOTOX was not effective in preventing the deleterious effects of AF.