Relationship with Nephrotoxicity of Abemaciclib in Rats: Protective Effect of Curcumin

Abemaciclib (ABE) has been reported to cause gastrointestinal toxicity. Therefore, it is important to investigate the question of whether abemaciclib administration causes nephrotoxicity in the gastrointestinal tract, and if so, what pathophysiological pathways it follows. In this study, the relationship between ABE administration and nephrotoxicity and the protective effect of Curcumin (CMN) was investigated. Forty female rats were equally divided into the sham, dimethyl sulfoxide (DMSO), CMN, abemaciclib and ABE+CMN groups. Aquaporin (AQP) 1-7, TNF-α, IL-1β, intercellular adhesion molecule (ICAM)-1, IL-10 and IL-37 levels in serum and kidney tissue homogenates were measured by ELISA. In addition, Urea and Creatinine were measured in serum samples. Furthermore, histopathological examination was performed in kidney tissues and Bax, Caspase-3 and Bcl-2 expression levels were determined immunohistochemically. The levels of AQP1-7 and IL-10 in the ABE group were partially lower than in the other groups, while the ratio of TNFα, IL-1β, MDA, caspase-3 and Bax/Bcl2 were high. In addition, kidney tissue was examined histopathologically. However, AQP1 and 7 levels in the ABE+CMN group were higher than in the ABE group, while TNF-α, IL-1β, MDA, Caspase-3 levels and Bax/Bcl2 ratio were low. In addition, the poor histopathological changes in the ABE group were largely restored in the ABE+CMN. The data presented that ABE in rats can adversely affect functions and histology of kidneys through the increase in oxidative stress, pro-inflammatory cytokines and apoptosis, but CMN therapy may be protective against the nephrotoxic effects of AB

The Effects of Some Phosphodiesterase 5 Inhibitors on Oxidative Stress, VEGF, BMP 2 and 9 in the Liver Tissue of Ovariectomized Rats

INTRODUCTION: Osteoporosis is an important health problem and there is no effective treatment yet. phosphodiesterase 5 inhibitors are promising agents for the treatment of osteoporosis. In this study, we aimed to determine the effects of phosphodiesterase 5 inhibitors (vardenafil, tadalafil, and udenafil) on bone morphogenic protein-2 and 9 (BMP-2 and 9), vascular endothelial growth factor (VEGF), and oxidative stress markers (malondialdehyde and CoQ10) in liver tissue of rats with ovariectomy-induced osteoporosis. METHODS: 50 Albino wistar female rats were randomly divided into 5 groups of 10 rats per group. Groups were the sham-operated, ovariectomise (OVEX), OVEX + Tadalafil, OVEX + udenafil and OVEX + vardenafil, respectively. VEGF, BMP-2 and 9 levels were measured by ELISA kits. To detect levels of MDA and CoQ10, we used high pressure liquid chromatography method. RESULTS: The levels of VEGF, BMP-2 and 9 levels in the groups that applied PDE-5 inhibitors were significantly higher than in the sham and OVEX groups. There was no significant difference between the OVEX+vardenafil and OVEX+udenafil groups in terms of VEGF, BMP-2 and 9 levels. The levels of MDA and CoQ10 were significantly lower in the groups that applied PDE5 inhibitors than in the OVEX group. When the histological and immunohistochemical results were examined, it was seen that angiogenesis was significantly higher in PDE-5 inhibitor groups. DISCUSSION AND CONCLUSION: In conclusion, we can say that these inhibitors may have positi ve effects on bone mineralization and remodelling by inducing the expression of VEGF, BMP-2 and 9 in liver tissue

Spectroscopic characterization, X-ray structure, antimicrobial activity and DFT calculations of novel dipicolinate copper(II) complex with 2,6-pyridinedimethanol

Novel dipicolinate complex of copper(II) ion, [Cu(dmp)(dpc)]center dot 0.8H(2)O [dmp: 2,6-pyridinedimethanol; dpc: dipicolinate or pyridine-2,6-dicarboxylate], has been prepared and fully characterized by single crystal X-ray structure determination. The central copper(II) ion is bonded to dpc and dmp ligands through pyridine nitrogen atom together with two oxygen atom, forming the distorted octahedral geometry. The complex molecules, connected via O-H center dot center dot center dot O hydrogen bonds, form a supramolecular structure. H(2)dpc, [Cu(dpc)(H2O)(3)] and [Cu(dmp)(dpc)]center dot 0.8H(2)O were screened for antimicrobial activity against Gram-positive, Gram-negative bacteria and yeast. H2dpc and [Cu(dpc)(H2O)(3)] exhibited antibacterial and antifungal activity, while [Cu(dmp)(dpc)]center dot 0.8H(2)O exhibited activity only for Gram-positive bacteria. The geometry optimization and EPR parameters were carried out using the following unrestricted hybrid density functionals: LSDA, BPV86, B3LYP, B3PW91, MPW1PW91, PBEPBE and HCTH. Although the supramolecular interactions have some influences on the molecular geometry in solid state phase, calculated data show that the predicted geometries can reproduce the structural parameters. The electronic station in the frontier orbitals of the copper complex calculated from the experimental data is compared to the results of time-depended DFT calculations with the polarizable continuum model. Calculated vibrational frequencies are consistent with the experimental IR data. (C) 2011 Elsevier B.V. All rights reserved