Effects of resveratrol and resveratrol delivered in liposome carrier system on penicillin-induced brain epileptic activity in male rats

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HMG-CoA reductase inhibitor rosuvastatin improves abnormal brain electrical activity via mechanisms involving eNOS

WOS: 000346243100032PubMed ID: 25453767Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors exert neuroprotective functions in animal models of neurodegenerative disorders. In view of these promising observations, we were interested in whether HMG-CoA reductase inhibition would affect epileptiform activity in the brain. To elucidate this issue, atorvastatin, simvastatin and rosuvastatin were administered orally at a dose of 20 mg/kg each for 3 days and their anti-epileptic activities were tested and compared in rats. Epileptiform activity in the brain was induced by an intracortical penicillin G injection. Among HMG-CoA reductase inhibitors, simvastatin-treatment was less effective in terms of spike frequency as compared with atorvastatin- and rosuvastatin-treated animals. Atorvastatin treatment reduced spike frequencies and amplitudes significantly throughout the experiment. However, the most pronounced anti-epileptic effect was observed in rosuvastatin-treated animals, which was associated with improved blood-brain barrier (BBB) integrity, increased expression of endothelial nitric oxide synthase (eNOS) mRNA and decreased expressions of pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition of eNOS activity with L-NG-Nitroarginine Methyl Ester (L-NAME) reversed the anti-epileptic effect of rosuvastatin significantly. However, L-NAME did not alter the effect of rosuvastatin on the levels of p53, Bax and caspase-3 mRNA expression. Here, we provide evidence that among HMG-CoA reductase inhibitors, rosuvastatin was the most effective statin on the reduction of epileptiform activity, which was associated with improved BBB permeability, increased expression of eNOS and decreased expressions of pro-apoptotic p53, Bax and caspase-3. Our observation also revealed that the anti-epileptic effect of rosuvastatin was dependent on the increased expression level of eNOS. The robust anti-epileptic effect encourages proof-of-concept studies with rosuvastatin in human epilepsy patients with hypercholesterolemia.European Molecular Biology Organization (EMBO); Turkish Academy of Sciences (TUBA/GEBIP)This work was supported by European Molecular Biology Organization (EMBO) (installation grant) and Turkish Academy of Sciences (TUBA/GEBIP)

Effects of paricalcitol and aliskiren combination therapy on experimental diabetic nephropathy model in rats

WOS: 000347728100009PubMed ID: 25532067Background/Aims: The aim of the present study was to investigate the effect of combination of aliskiren with paricalcitol on experimental diabetic nephropathy (DN) model in rats. Methods: Forty male Sprague Dawley rats were divided into 5 groups of 8 rats each, namely the control (Group C), diabetes (Group D), aliskiren (Group A), paricalcitol (Group P), and aliskiren plus paricalcitol (Group A+P) groups. Aliskiren was given by oral-gavage at a dose of 50 mg/kg/day once daily for 12 weeks. Paricalcitol was given by intraperitoneally at a dose of 0,4 mu g/kg/three day of week for 12 weeks. Renal function parameters, oxidative stress biomarkers, mRNA expression of renin-angiotensin system parameters and kidney histology were determined. Results: Group A+P had lower mean albumin-to-creatinine ratio (ACR) (p=0.004) as well as higher creatinine clearance (CCr) (p<0.005) than the diabetic rats (Group D). Combination therapy significantly increased CCr (Group A+P vs Group A, p<0.005; Group A+P vs Group P, p=0.022) and reduced ACR (Group A+P vs Group A, p=0.018; Group A+P vs Group P, p<0.005) when compared to monotherapy. Serum malondialdehyde levels were significantly lower (p=0.004); glutathion levels (p=0.003), glutathion peroxidase (p=0.004) and superoxide dismutase (p<0.005) activities were significantly higher in group A+P than in group D. The mean scores of mRNA expression of renin (p<0.005), angiotensin II (p=0.012) and angiotensin type 1 receptor (p=0.018) in group A+P were significantly lower. Although combination therapy showed no additional effect on oxidative system, renin-angiotensin system and renal histology, aliskiren plus paricalcitol significantly decreased interstitial fibrosis volume when compared to monotherapy (Group A+P vs Group A, p<0.005; Group A+P vs Group P, p=0.002). Conclusion: Our data seem to suggest a potential role of aliskiren plus paricalcitol acting synergystically for reducing the progression of diabetic nephropathy in an experimental rat model.Scientific and Technical Research Council of Turkey [TUBITAK 111S299]This work was supported by The Scientific and Technical Research Council of Turkey (TUBITAKTUBITAK SBAG 111S299). The authors would like to acknowledge the contributions of Prof. Dr. Mujdat Uysal. We thank Burak Caglayan and Mustafa Caglar Beker for expert technical assistance

Preclinical Studies on Convalescent Human Immune Plasma-Derived Exosome: Omics and Antiviral Properties to SARS-CoV-2

The scale of the COVID-19 pandemic forced urgent measures for the development of new therapeutics. One of these strategies is the use of convalescent plasma (CP) as a conventional source for passive immunity. Recently, there has been interest in CP-derived exosomes. In this report, we present a structural, biochemical, and biological characterization of our proprietary product, convalescent human immune plasma-derived exosome (ChipEXO), following the guidelines set forth by the Turkish Ministry of Health and the Turkish Red Crescent, the Good Manufacturing Practice, the International Society for Extracellular Vesicles, and the Gene Ontology Consortium. The data support the safety and efficacy of this product against SARS-CoV-2 infections in preclinical models

Preclinical Studies on Convalescent Human Immune Plasma-Derived Exosome: Omics and Antiviral Properties to SARS-CoV-2.

The scale of the COVID-19 pandemic forced urgent measures for the development of new therapeutics. One of these strategies is the use of convalescent plasma (CP) as a conventional source for passive immunity. Recently, there has been interest in CP-derived exosomes. In this report, we present a structural, biochemical, and biological characterization of our proprietary product, convalescent human immune plasma-derived exosome (ChipEXO), following the guidelines set forth by the Turkish Ministry of Health and the Turkish Red Crescent, the Good Manufacturing Practice, the International Society for Extracellular Vesicles, and the Gene Ontology Consortium. The data support the safety and efficacy of this product against SARS-CoV-2 infections in preclinical models