Phosphodiesterase type 5 inhibition attenuates cyclosporine A induced nephrotoxicity in mice

WOS: 000352110200002PubMed: 25420893We 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-beta 1), 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-beta 1, 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.Scientific and Technological Research Council of Turkey (TUBITAK-TOVAG), Ankara, TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [110 O 402]Our study was funded by the Scientific and Technological Research Council of Turkey (TUBITAK-TOVAG; Project no. 110 O 402), Ankara, Turkey

The effects of aflatoxin and sodium bentonite combined and alone on some blood electrolyte levels in broiler chickens

The aim of the study is to determine the effects of aflatoxin and sodium bentonite given alone and in combination on some of blood electrolyte levels in broiler chicks. For this aim, 72 male one-day-old Avian broiler chicks were used. The animals were separated into 6 groups, as one control (Group 1) and the others trial (Groups 2 to 6). While commercial feed was given to Group 1 (control), the other groups received feed containing 0.25% sodium bentonite, 0.50% sodium bentonite, 1 ppm aflatoxin (approximately, 85% B-1, 10% B-2, 3% G(1) and 2% G(2)), 1 ppm aflatoxin with 0.25% sodium bentonite and I ppm aflatoxin with 0.50% sodium bentonite (Groups 2-6), respectively, for 45 days. Blood samples were taken on the 15(th), 30(th) and 45(th) days of the study and the sodium, potassium, chloride, phosphorus and calcium levels in serum were analyzed. At the end of the study, it was determined that aflatoxin caused a decrease in calcium and phosphorous levels. On the other hand, it was observed that sodium bentonite in the feed caused a decrease in both of these electrolyte levels, even though these decreases were higher in the groups that received aflatoxin alone

Effects of MOLDSTOP® on aflatoxicosis in quails

This study was conducted to evaluate the toxic effects of aflatoxin (AF) on the growth performance of quails, and to determine the preventive efficacy of MOLDSTOP® (calcium formate, calcium propionate, citric acid, sorbic acid, acetic acid, and carrier). A total of 60 one-day-old quails (Coturnix coturnix japonica) of both sexes were equally divided into four experimental groups each comprising of five replicates of three birds. The supplementation of diet with AF decreased significantly (P<0.001) the feed consumption. The 0.5% addition of MOLDSTOP® to the AF diet did not significantly prevent or reduce negative effect of AF on feed consumption at any time period. Light microscopic examination demonstrated that the addition of MOLDSTOP® did not decrease fat deposition caused by the toxin, and besides, an electron microscopic examination indicated the reorganisation in the endoplasmic reticulum and increase in the number of ribosomes and polisomes compared to the AF plus MOLDSTOP® group. The data indicated that the addition of MOLDSTOP® to diets containing AF did not prevent the negative effects of AF observed in the quail

Computational Analysis of a Zn-Bound Tris(imidazolyl) Calix[6]arene Aqua Complex: Toward Incorporating Second-Coordination Sphere Effects into Carbonic Anhydrase Biomimetics

Molecular dynamics simulations and quantum-mechanical calculations were performed to characterize a supramolecular tris­(imidazolyl) calix[6]­arene Zn²⁺ aqua complex, as a biomimetic model for the catalyzed hydration of carbon dioxide to bicarbonate, H₂O + CO₂ → H⁺ + HCO₃^–. On the basis of potential-of-mean-force (PMF) calculations, stable conformations had distorted 3-fold symmetry and supported either one or zero encapsulated water molecules. The conformation with an encapsulated water molecule is calculated to be lower in free energy than the conformation with an empty cavity (Δ<i>G</i> = 1.2 kcal/mol) and is the calculated free-energy minimum in solution. CO₂ molecule partitioning into the cavity is shown to be very facile, proceeding with a barrier of 1.6 kcal/mol from a weak encounter complex which stabilizes the species by about 1.0 kcal/mol. The stabilization energy of CO₂ is calculated to be larger than that of H₂O (ΔΔ<i>G</i> = 1.4 kcal/mol), suggesting that the complex will preferentially encapsulate CO₂ in solution. In contrast, the PMF for a bicarbonate anion entering the cavity is calculated to be repulsive in all nonbonding regions of the cavity, due to the diameter of the calix[6]­arene walls. Geometry optimization of the Zn-bound hydroxide complex with an encapsulated CO₂ molecule showed that multiple noncovalent interactions direct the reactants into optimal position for nucleophilic addition to occur. The calixarene complex is a structural mimic of the hydrophilic/hydrophobic divide in the enzyme, providing a functional effect for CO₂ addition in the catalytic cycle. The results show that Zn-binding calix[6]­arene scaffolds can be potential synthetic biomimetics for CO₂ hydration catalysis, both in terms of preferentially encapsulating CO₂ from solution and by spatially fixing the reactive species inside the cavity