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General Physiology and Biophysics


Volume 37, 2018, No. 1

Content:


 
Inhibition of PDE4 by low doses of rolipram induces changes in lipid and protein components of mice heart.
Sevgi Türker-Kaya 1), İpek Komsuoğlu Celikyurt, Umut Celikyurt, Aygül Kına

1)Department of Biology, Faculty of Arts and Sciences, Kocaeli University, 41380, Kocaeli, Turkey. sevgitrkr@gmail.com.

There is significant increasing interest in phosphodiesterase-4 (PDE4) inhibition in treatment of cardiovascular diseases. Related with this, research has focused on cellular, biochemical, molecular and structural changes in heart tissue induced by PDE4s inhibitors. However, for their clinical applicability additional studies are still needed. Fourier transform infrared spectroscopy offers promising approach to contribute such issue due to its ability in detection the changes in biomolecules. By utilizing this method, we examined the effects of PDE4 inhibition by rolipram at 0.05 mg/kg and 0.1 mg/kg doses on content of lipids and proteins, and fluidity, order and packing of membranes in naive mice heart. In treated groups, there was a significant decrease in unsaturated, saturated lipids, cholesterol esters, fatty acids, phospholipids and triacylgylcerols obtained from CH2, C=O, olefinic=CH, and COO- areas, and CH2/lipid, C=O/lipid, olefinic=CH/lipid, and COO–/lipid ratios. Additionally, olefinic=CH area and olefinic=CH/lipid ratio may suggest decreased lipid peroxidation, confirmed by thiobarbituric acid assay. Also, a higher degree of membrane order, slight increase in membrane fluidity and differences in membrane packing were obtained. Amide I and II areas and RNA/protein ratios showed that variation in protein content is not correlated with applied concentration. Analysis of amide I mode predicted alterations in secondary structures like an increase in random coils and decrease in alpha-helices. Moreover, all groups were successfully discriminated by cluster analysis. The corresponding results may help to understand the potential effects of PDE4 inhibition by rolipram.

How to cite (APA format):
Türker-Kaya, S, Komsuoğlu Celikyurt, İ, Celikyurt, U, Kına, A. (2018). Inhibition of PDE4 by low doses of rolipram induces changes in lipid and protein components of mice heart. General Physiology and Biophysics, 37(1), 1-12.


 
Left-right asymmetry in firing rate of extra-retinal photosensitive neurons in the crayfish.
José Pacheco-Ortiz 1), Juan Sánchez-Hernández, Leonardo Rodríguez-Sosa, Gabina Calderón-Rosete, Edgar Villagran-Vargas

1)Faculty of Science, Autonomous University of the State of Mexico, Mexico City, Mexico. lrsosa@unan.mx.

The purpose of this paper is to explore the firing rate of the caudal photoreceptors (CPRs) from the sixth abdominal ganglion of the crayfish Cherax quadricarinatus. We use simultaneous extracellular recordings on left and right CPR in the isolated ganglion (n = 10). The CPRs showed an asymmetry in the spontaneous activity and light-induced response. In darkness, we observed one subgroup (70%) in which the left CPR (CPR-L) and right CPR (CPR-R) had spontaneous firing rates with a median of 18 impulses/s and 6 impulses/s, respectively. In another subgroup (20%), the CPR-R had a median of 15 impulses/s and the CPR-L had 8 impulses/s. In both groups, the differences were significant. Furthermore, the CPRs showed an asymmetrical photoresponse induced by a pulse of white light (700 Lux, 4 s). In one subgroup (30%), the CPR-L showed light-induced activity with a median of 73%, (interquartile range, IQR = 51), while the CPR-R had a median of 41%, (IQR = 47). In another subgroup (70%), the CPR-R showed a median of 56%, (IQR = 51) and the CPR-L had a median of 42%, (IQR = 46). In both groups, the differences were significant. Moreover, we observed a differential effect of temperature on CPR activity. These results suggest a functional asymmetry in both activities from left and right CPRs. These CPR activity fluctuations may modulate the processing of information by the nervous system.

How to cite (APA format):
Pacheco-Ortiz, J, Sánchez-Hernández, J, Rodríguez-Sosa, L, Calderón-Rosete, G, Villagran-Vargas, E. (2018). Left-right asymmetry in firing rate of extra-retinal photosensitive neurons in the crayfish. General Physiology and Biophysics, 37(1), 13-21.


 
Therapeutic effects of N-acetyl-L-cysteine on liver damage induced by long-term CCl4 administration.
Oľga Otrubová 1), Ladislav Turecký, Oľga Uličná, Pavol Janega, Ján Luha, Jana Muchová

1)Department of Occupational Medicine and Toxicology, National Toxicological Information Centre, University Hospital Bratislava, Faculty of Medicine, Comenius University, Bratislava, Slovakia. jana.muchova@fmed.uniba.sk.

N-acetyl-L-cysteine (NAC) is a drug routinely used in several health problems, e.g. liver damage. There is some information emerged on its negative effects in certain situations. The aim of our study was to examine its ability to influence liver damage induced by long-term burden. We induced liver damage by CCl4 (10 weeks) and monitored the impact of parallel NAC administration (daily 150 mg/kg of b.w.) on liver morphology and some biochemical parameters (triacylglycerols, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, bile acids, proteins, albumins and cholinesterase). NAC significantly decreased levels of bile acids and bilirubin in plasma and triacylglycerols in liver, all of them elevated by impairment with CCl4. Reduction of cholesterol induced by CCl4 was completely recovered in the presence of NAC as indicated by its elevation to control levels. NAC administration did not improve the histological parameters. Together with protective effects of NAC, we found also its deleterious properties: parallel administration of CCl4 and NAC increased triacylglycerols, ALT and AST activity and significantly increased plasma cholinesterase activity. We have observed nonsignificantly increased percentage of liver tissue fibrosis. Our results have shown that NAC administered simultaneously with liver damaging agent CCl4, exhibits not only protective, but also deleterious effects as indicated by several biochemical parameters.

How to cite (APA format):
Otrubová, O, Turecký, L, Uličná, O, Janega, P, Luha, J, Muchová, J. (2018). Therapeutic effects of N-acetyl-L-cysteine on liver damage induced by long-term CCl4 administration. General Physiology and Biophysics, 37(1), 23-31.


 
The contribution of noradrenergic nerves to the vasoconstrictor response during local cooling of leg and forearm skin in humans.
Ramzi Al-horani 1), Mukhallad Mohammad

1)Department of Exercise Science, Yarmouk University, Irbid, Jordan. raalhorani@yu.edu.jo.

This study investigated the noradrenergic contribution during the cutaneous vasoconstrictor response to local cooling in the leg and forearm. On each limb, one site was perfused with Yoh/Prop to block the postsynaptic adrenoceptors and another with Lactated Ringer’s (control) using microdialysis. Blood flow was measured by Laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as LDF units divided by the mean arterial pressure. After baseline measures, skin was locally cooled to 24°C. Basal CVC was similar at all sites in the leg and forearm (all p > 0.1). During the first 10 min of local cooling, CVC was reduced in the leg (p < 0.005) and unchanged in the forearm control sites (p = 0.2). Yoh/Prop induced an increased CVC in the leg and forearm to a similar level (39.2 ± 11.5, and 41.3 ± 3.3%CVC, respectively; p < 0.35). Late during local cooling, the vasoconstriction was attenuated in the leg and forearm at Yoh/Prop (–38.2 ± 5.3 –37.1 ± 5.3%CVC, respectively; p = 0.5) compared to control sites (–69.1 ± 5.8 vs. –54.5 ± 6.4%CVC, respectively; p < 0.005). Noradrenergic contribution was greater in the leg than the forearm during the late vasoconstrictor response (p = 0.006). These data indicate that the leg skin can induce greater vasoconstriction than forearm during local cooling, possibly via higher noradrenergic sensitivity in the leg skin.

How to cite (APA format):
Al-horani, R, Mohammad, M. (2018). The contribution of noradrenergic nerves to the vasoconstrictor response during local cooling of leg and forearm skin in humans. General Physiology and Biophysics, 37(1), 33-40.


 
Ca2+-dependent calcineurin/NFAT signaling in β-adrenergic-induced cardiac hypertrophy.
Ali Khalilimeybodi 1), Alireza Daneshmehr, Babak Sharif Kashani

1)Department of Mechanical Engineering, College of Engineering, University of Tehran, Tehran, Iran. Daneshmehr@ut.ac.ir.

Ca2+ is an important mediator in the β-adrenergic-induced cardiac hypertrophy. The β-adrenergic stimulation alters the Ca2+ transient characteristics including its oscillation frequency, diastolic and systolic levels which lead to the CaN activation and subsequent NFAT-dependent hypertrophic genes transcription. Moreover, β-adrenergic-induced alterations in PKA and GSK3β kinase activities in both the cytosol and the nucleus regulate NFAT nuclear translocation and contribute in its hypertrophic response. Due to the complex nature of CaN/NFAT signaling in cardiac cells, we use a computational approach to investigate the β-adrenergic-induced CaN/NFAT activation in the cardiac myocytes. The presented model predicts well the main physiological characteristics of CaN/NFAT signaling in accordance with the experimental observations. The presented model establishes the previous experimental and mathematical results on the principal role of Ca2+ oscillation frequency in the CaN/NFAT signaling and shows that increase in Ca2+ oscillation frequency enhances CaN activity and its sensitivity to low ISO concentrations. The model illustrates that in addition to the known ISO effect on Ca2+ transient amplitude, ISO-induced alterations in Ca2+ oscillation frequency, PKA and GSK3β kinase activities also greatly affect the β-adrenergic-induced NFAT activity. We also found that PKA has both pro-hypertrophic and anti-hypertrophic effects on NFAT activation and is the main kinase in ISO-induced NFAT activation.

How to cite (APA format):
Khalilimeybodi, A, Daneshmehr, A, Sharif Kashani, B. (2018). Ca2+-dependent calcineurin/NFAT signaling in β-adrenergic-induced cardiac hypertrophy. General Physiology and Biophysics, 37(1), 41-56.


 
DNA–DOPE–gemini surfactants complexes at low surface charge density: from structure to transfection efficiency.
Lukáš Hubčík 1), Dominika Galliková, Petra Pullmannová, Ľubica Lacinová, Zdena Sulová, Mária Hanulová, Sergio Funari, Ferdinand Devínsky, Daniela Uhrikova

1)Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia. hubcik@fpharm.uniba.sk.

DNA condensation, structure and transfection efficiency of complexes formed by gemini surfactants alkane-α,ω-diyl-bis(dodecyldimethylammonium bromide)s (CnGS12, n = 3, 6 and 12 is the number of alkane spacer carbons), dioleoylphosphatidylethanolamine (CnGS12/DOPE = 0.3 mol/mol) and DNA at low surface charge density were investigated through different techniques. Small angle X-ray diffraction showed a condensed lamellar phase with marked dependence of DNA-DNA distance on (+/-) charge ratio. High ionic strength of hydrating medium screens the interaction DNA - CnGS12/DOPE and complexed DNA represented maximally ~ 45–60% of total DNA in the solution as derived from fluorescence and UV-VIS spectroscopy. The in vitro transfection efficiency of CnGS12/DOPE liposomes on mammalian HEK 293 cell line was spacer length-dependent. C12GS12/DOPE/DNA complexes exhibited the best transfection efficiency (~ 18% GFP-expressing cells relative to all viable cells) accompanied by ~ 89% cell viability.

How to cite (APA format):
Hubčík, L, Galliková, D, Pullmannová, P, Lacinová, Ľ, Sulová, Z, Hanulová, M, Funari, S, Devínsky, F, Uhrikova, D. (2018). DNA–DOPE–gemini surfactants complexes at low surface charge density: from structure to transfection efficiency. General Physiology and Biophysics, 37(1), 57-69.


 
Action potential propagation: ion current or intramembrane electric field?.
Albert Martí 1), Juan Pérez, Jordi Madrenas

1)Department of Electronics Engineering, Universitat Politècnica de Catalunya, Campus Nord, Building C4. C. Jordi Girona, 1-3, 08034 Barcelona, Catalunya, Spain. albert.marti.edo@gmail.com.

The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

How to cite (APA format):
Martí, A, Pérez, J, Madrenas, J. (2018). Action potential propagation: ion current or intramembrane electric field?. General Physiology and Biophysics, 37(1), 71-82.


 
Resuscitative therapy with erythropoietin reduces oxidative stress and inflammatory responses of vital organs in a rat severe fixed-volume hemorrhagic shock model.
Mina Ranjbaran 1), Mehri Kadkhodaee, Behjat Seifi, Reza Mirzaei, Parisa Ahghari

1)Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. kadkhodm@tums.ac.ir.

Hemorrhagic shock (HS) still has a high mortality rate and none of the known resuscitative regimens completely reverse its adverse outcomes. This study investigated the effects of different models of resuscitative therapy on the healing of organ damage in a HS model. Male Wistar rats were randomized into six groups: Sham, without HS induction; HS, without resuscitation; HS+Blood, resuscitation with the shed blood; HS+Blood+NS, resuscitation with blood and normal saline; HS+Blood+RL, resuscitation with blood and Ringer’s lactate; EPO, erythropoietin was added to the blood and RL. Blood and urine samples were obtained 3 h after resuscitation. Kidney, liver and brain tissue samples were harvested for multiple organ failure evaluation. Survival rate was the highest in the Sham, EPO and HS+Blood+RL groups compared to others. Plasma creatinine concentration, ALT, AST, urinary NAG activity and renal NGAL mRNA expression significantly increased in the HS+Blood+RL group compared to the Sham group. There was a significant increase in tissue oxidative stress markers and pro-inflammatory cytokines in HS+Blood+RL group compared to the Sham rats. EPO had more protective effects on multiple organ failure compared to the HS+Blood+RL group. EPO, as a resuscitative treatment, attenuated HS-induced organ damage. It seems that it has a potential to be attractive for clinical trials.

How to cite (APA format):
Ranjbaran, M, Kadkhodaee, M, Seifi, B, Mirzaei, R, Ahghari, P. (2018). Resuscitative therapy with erythropoietin reduces oxidative stress and inflammatory responses of vital organs in a rat severe fixed-volume hemorrhagic shock model. General Physiology and Biophysics, 37(1), 83-92.


 
Stability studies of endocrine disrupting tributyltin and triphenyltin compounds in an artificial sea water model.
Ladislav Novotny 1), Leyla Sharaf, Mohammed Abdel-Hamid, Július Brtko

1)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, Kuwait City, Kuwait. novotny@hsc.edu.kw.

Triorganotins belong to toxic components present predominantly in antifouling paints for marine vessels. Tributyltin/triphenyltin at pico- or nanomolar concentrations in sea water are known to induce an irreversible sexual abnormality in females of over 190 marine species, an "imposex" phenomenon – the superimposition of male genitalia on a female. Moreover, trialkyltins and triaryltins function as potent nuclear retinoid X receptors (RXR) agonists. In mammals, triorganotin compounds induce immunosuppressive, metabolic, reproductive or developmental effects. Toxic effects of triorganotins warrant the need for monitoring of their long-lasting presence in the environment. This study brings novel data on the stability of two triorganotin compounds in artificial sea water model obtained by applying ultra-pressure liquid chromatography (UPLC) and gas chromatography-mass spectrometry (GC-MS) methods. Stability of tributyltin and triphenyltin chlorides was studied for 180 days and the degradation kinetic parameters were obtained. Tributyltin chloride was the less stable with the degradation kinetic parameters Kdeg = 0.00014 day–1 and t1/2 = 4950 days (13.6 years). Kdeg of the more stable triphenyltin chloride was determined to be Kdeg = 0.00006 day–1 with t1/2 = 11550 days (31.6 years). Since similar stability data of triorganotin compounds were not published previously, we report high stability for both tested compounds, which indicates a significant environmental problem when these substances enter sea water and later coastal sediments.

How to cite (APA format):
Novotny, L, Sharaf, L, Abdel-Hamid, M, Brtko, J. (2018). Stability studies of endocrine disrupting tributyltin and triphenyltin compounds in an artificial sea water model. General Physiology and Biophysics, 37(1), 93-99.


 
Cytotoxicity of propolis nanopreparations in cancer cell monolayers: multimode of action including apoptotsis and nitric oxide production.
Mahmoud Sherif 1), Taha Rehab, Zayed Hamdia, Vladmir Torchilin

1)1Biophysics and Laser Science Unit, Research Institute of Ophthalmology, Giza, Egypt. sheri_sm@yahoo.com.

Natural products are invaluable resource of anticancer drug discovery. They generally viewed as safe but weak, within the framework of nanotechnology, they can serve as template for potent anticancer drugs. We first evaluated the cytotoxic activity of different propolis extracts (water, 70% ethanol, absolute ethanol and hexane) in many cancer cell lines, then the solid nanoparticles from the organic solvent extracts were prepared and their cytotoxicity was evaluated as well. Finally, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes were prepared from the most cytotoxic organic solvent extract and their cytotoxicity was also evaluated. All results collectively showed that hexane extract and its solid nanoparticles as well as its liposomal form exhibited high cytotoxic activity. DPPC/DOPC-hexane extract cytotoxicity selectively depends on the cell line and DOPC liposomal form was characterized by reduced IC50 compared with the other preparations/extracts, the average IC50 value is 165.8 ± 3 µg/ml. The antiproliferative activity of propolis was associated to multiple modes of actions including apoptosis and nitric oxide production and as indicated by the HPLC and FTIR results, it is functioning in many propolis ingredients rather than a single component and influenced by the presence of more lipophilic components within the extract and not by the extract mass yield. These results may have an impact on the multidrug resistivity issue.

How to cite (APA format):
Sherif, M, Rehab, T, Hamdia, Z, Torchilin, V. (2018). Cytotoxicity of propolis nanopreparations in cancer cell monolayers: multimode of action including apoptotsis and nitric oxide production. General Physiology and Biophysics, 37(1), 101-110.


 
Water-soluble quercetin modulates the choleresis and bile lipid ratio in rats.
Tatiana Vovkun 1), Petro Yanchuk, Lidiya Shtanova, Stanislav Veselskiy, Natalia Filimonova, Anatoly Shalamay, Volodymyr Vedmid

1)Educational and Scientific Centre, Institute of Biology and Мedicine, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine. shtanova@ukr-net.

Water-soluble analogue of quercetin, corvitin is used in patients with myocardial infarction as blocker of 5-lipoxygenase. However, its effects on secretion, lipid content and physico-chemical properties of bile have not been understood yet. We investigated the effect of corvitin, applied in different doses, on the level of bile flow, the content of bile free and esterified cholesterol, phospholipids, triacylglycerols, and free fatty acids. In order to determine stability of the bile colloidal system, we examined the relationship between different lipid components. The rats were injected intraportally with a bolus of corvitin. At doses of 2.5, 5, and 10 mg/kg, the latter increased bile flow and concentration of total cholates, as well as free fatty acids. Corvitin (5 mg/kg) elevated phospholipids and cholesterol content, but at a dose of 10 mg/kg it increased the concentration of bile cholesterol esters and triacylglycerols. Corvitin applied at doses of 2.5 and 10 mg/kg increased total cholates/cholesterol ratio, but at a dose of 10 mg/kg, the drug reduced cholesterol / esterified cholesterol ratio. The results suggest that corvitin exerts choleretic effect and improves stability of bile colloidal system.

How to cite (APA format):
Vovkun, T, Yanchuk, P, Shtanova, L, Veselskiy, S, Filimonova, N, Shalamay, A, Vedmid, V. (2018). Water-soluble quercetin modulates the choleresis and bile lipid ratio in rats. General Physiology and Biophysics, 37(1), 111-120.