Bis(4,4 -dimethyl-2,2-bipyridine)oxidovanadium(IV...

Research ArticleBis(441015840-dimethyl-221015840-bipyridine)oxidovanadium(IV)Sulfate Dehydrate Potential Candidate for ControllingLipid Metabolism

Renata Francik1 Jadwiga Kryczyk-KozioB2 SBawomir Francik3

Ryszard GryboV4 andMirosBaw KroVniak2

1Department of Bioorganic Chemistry Chair of Organic Chemistry Jagiellonian University Medical College Krakow Poland2Department of Food Chemistry and Nutrition Jagiellonian University Medical College Krakow Poland3Department of Mechanical Engineering and Agrophysics Faculty of Production Engineering and EnergeticsUniversity of Agriculture in Krakow Krakow Poland4Faculty of Chemistry Jagiellonian University Krakow Poland

Correspondence should be addressed to Jadwiga Kryczyk-Kozioł jadwigakryczykgmailcom

Received 12 March 2017 Accepted 10 April 2017 Published 26 April 2017

Academic Editor Sergio Claudio Sacca

Copyright copy 2017 Renata Francik et alThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Vanadium is a trace elementmainly connected with regulation of insulinmetabolismwhich is particularly important in diabetes Inrecent years organic complexes of vanadium seem to be more interesting than inorganic salts Nevertheless the effect of vanadiumon lipid metabolism is still a problematic issue therefore the main purpose of this study was to investigate the effect of 3 organiccomplexes of vanadium such as sodium (221015840-bipyridine)oxidobisperoxovanadate(V) octahydrate bis(221015840-bipyridine)oxidovana-dium(IV) sulfate dehydrate and bis(441015840-dimethyl-221015840-bipyridine)oxidovanadium(IV) sulfate dihydrate in conjunction with high-fat as well as control diet in nondiabetes model on the following lipid parameters total cholesterol triglycerides and high densitylipoprotein as well as activity of paraoxonase 1 All of these parameters were determined in plasma of Wistar rats The mostsignificant effect was observed in case of bis(441015840-dimethyl-221015840 bipyridine)oxidovanadium(IV) sulfate dehydrate in rats fed withhigh-fat diet Based on our research bis(441015840-dimethyl-221015840-bipyridine)oxidovanadium(IV) sulfate dihydrate should be the aim offurther research and perhaps it will be an important factor in the regulation of lipid metabolism

1 Introduction

Vanadium is a trace element on which a lot of attentionwas paid in context of diabetes Initially vanadium com-pounds were supposed to be insulin mimetic however nowthis element is mainly considered as a mean of increasingsensitivity of hepatocytes and myocytes on the effect of thishormone Regulation by vanadium among other activities ofthe protein tyrosine phosphatase-1B (PTP-1B) is particularlyimportant [1] Probably the excessive activity of protein tyro-sine phosphatase can affect insulin resistance [2]The effect ofvanadium compounds on glucose transport involving proteinGLUT-4 was indicated too [3 4] What is more this elementactivates also enzymes involved in glycolysis and glycogenesisas well as lipid metabolism [5]

Nowadays the effect of vanadium on carbohydratemetabolism is getting better known while the effect on lipidmetabolism is still a problematic issue Study indicating dys-lipidemic properties of organic complexes of vanadium wasconducted in diabetes model [6] nevertheless there is stilllack of research evaluating these properties in nondiabetesmodel Disturbance of lipid metabolism is a basic factor indevelopment of cardiovascular diseases which are currentlyone of the main reasons for mortality [7 8] Statins arecommon drugs used in treatment of such patients Howeverthere is an urgent need of search for alternative formsof treatment for patients with contraindications of statinsTherefore the main purpose of this study was to investigatethe effect of 3 organic vanadium complexes on selected lipidparameters in rats fed with a high-fat diet

HindawiBioMed Research InternationalVolume 2017 Article ID 6950516 5 pageshttpsdoiorg10115520176950516

2 BioMed Research International

Paraoxonase 1 (PON1) is an enzyme involved in lipidmetabolism for example by limiting HDL and LDL oxi-dation Moreover this enzyme is also known for anti-inflammatory properties [9] Meta-analyses indicated a cor-relation between risk of cardiovascular disease and PON1activity among people independent of age or ethnicity [1011] On the other hand inadequate diet can contribute toreduction level of expression of that enzyme [12] Taking intoaccount a protective role of PON1 in cardiovascular diseaseswe found it also necessary to evaluate the influence of thesevanadium complexes on this parameter Because this enzymeis calcium-dependent we analyzed this element as well

2 Materials and Methods

21 Reagents The reagentswere purchased fromSigmaAldrichChemical Company (Steinheim Germany) and Avantor Per-formance Materials Poland SA

22 Synthesis of Vanadium Complexes In this study the fol-lowing complexes were used sodium (221015840-bipyridine)oxi-dobisperoxidovanadate(V) octahydrate Na[VO(O2)2(22

1015840-bpy)]sdot8H2O marked as V (4539 gmol) bis(221015840-bipyri-dine)oxidovanadium(IV) sulfate dihydrate [VO(SO4)(22

1015840-bpy)]sdot2H2O marked as B (51121 gmol) and bis(441015840-dimethyl-221015840-bipyridine)oxidovanadium(IV) sulfate dihy-drate [VO(441015840-Me-221015840-bpy)2]SO4sdot2H2O marked as Bm(56721 gmol) Synthesis of the first compoundVwas described[13] In turn synthesis of compound B was described [14] Incase of Bm compound process of synthesis was similar to Bcomplex except molar ratio of ligand to vanadium which was2 1 The purity of all analyzed complexes was confirmed bymicroanalysis and IR spectroscopy

23 Animals In the experiment male Wistar rats aged3 months and weighing 250 plusmn 15 g were divided into8 groups of 6 animals During the time of experiment(5 weeks) each group of animals was fed with differentdiet group CN standard diet (starchmdash62 caseinmdash20oilmdash50 calcium carbonatemdash28 Ca3(PO4)2mdash29lecithinmdash10 NaClmdash03 cellulosemdash47 minerals andvitamins mixmdash10 MgOmdash007 and K2SO4mdash023)group CV standard diet + vanadium complex V groupCB standard diet + vanadium complex B group CBmstandard diet + vanadium complex Bm group AN highfatty diet (starchmdash32 caseinmdash20 oilmdash50 lardmdash30calcium carbonatemdash28 Ca3(PO4)2mdash29 lecithinmdash10NaClmdash03 cellulosemdash47 minerals and vitaminsmixmdash10 MgOmdash007 and K2SO4mdash023) group AVhigh fatty diet + vanadium complex V group AB high fattydiet + vanadium complex B group ABm high fatty diet+ vanadium complex Bm In all vanadium treated groupstested complexes were administered by gavage once a dayduring 5 weeks in the dose of 20mgkg body mass

All animals had free access to feed and water and werekept in a room with a constant temperature of 23∘C and50ndash60 humidity with a 12-hour daynight cycle After 5weeks the animals were anesthetized This experience wasconducted with an approval of I Local Ethics Committee for

Animal Experiments of Jagiellonian University in Cracownumber 802009 17092009

24 Blood Preparation Blood samples were taken from aortainto heparinized tubes and then centrifuged (at 2500timesg for 15minutes at 4∘C) to obtain plasma which was kept frozen (atminus80∘C) until further analyses

25 Biochemical Parameters Biochemical analysis was doneusing standard biochemical analyzer Alize BioMerieux withstandard kits (Camdash61041 TCHOLmdash61218 TGmdash61236HDLmdash61001 and 61002) from BioMerieux Thus theobtained results were compared with Control Serum 1ODC0003 and Control Serum 2 ODC0004 (OLYMPUS)

26 Paraoxonase 1 Activity (PON1) in Plasma Paraoxonase1 (PON1) activity was determined by modified Eckersonmethod [15] A mixture of 025M Tris buffer (pH 8) and01M paraoxon in a volume ratio of 19 1 (vv) was addedto samples Then the absorbance was measured at 412 nmduring 2 minutes PON1 activity was estimated based onchanges in concentration of substrate

27 Statistical Analysis Weused two-way analysis of variance(ANOVA) in order to verify if the examined factors (explana-tory variables) influence the observed (dependent) variables[16] Before this we had checked if the main assumptionsconcerning normal distribution of dependent variable withingroups as well as homogeneity of variance were met [17]Normal distribution was verified by Shapiro-Wilk test whilehomogeneity of variancewas verified by Levenersquos test In turnBox-Cox transformationwas used for variables which did notmeet ANOVA assumptions [17 18]

Analysis of variance was conducted for each of the fol-lowing dependent variables Ca [mmoll] TCHOL [mmoll]TG [mmoll] HDL [mgdL] and PON1 [Umg protein]Intragroup factors were the type of diet (X1-diet) and typeof supplement (X2-supplement) Type of diet (X1-diet) had2 levels (C and A) in turn type of supplement (X2-supplement) had 4 levels (N B V and Bm)

Tukeyrsquos test was used to indicate homogeneous groups(marked by identical letters) All analyses were conducted atsignificance level 119901 = 005 Obtained data were statisticallyanalyzed using the STATISTICA (StatSoft Inc (2011) version10 httpwwwstatsoftcom)

Based on Levenersquos test 3 variables such as TCHOL[mmoll] TG [mmoll] and PON1 [Umg protein] did notmeet assumption of homogeneity of variance Thereforefor them Box-Cox transformation was made after whichvariablesmet the assumption concerning normal distribution(Shapiro-Wilk test) and homogeneity of variance (Levenersquostest) at significance level 119901 = 005 Then two-way analysisof variance (ANOVA) was used

3 Results

The results are summarized in Table 1 All parameters wereanalyzed in plasma of rats Bm vanadium complex in controldiet (CBm) statistically increased (119901 lt 005) concentrationof calcium compared to control diet (CN) In case of V

BioMed Research International 3

Table 1 Biochemical parameters Data are presented as means from independent measurements plusmn standard deviation (SD)

X1-diet X2-supplement Name group Ca [mmoll] TCHOL [mmoll] TG [mmoll] HDL [mgdL] PON1 [Umg protein]C N CN 313 plusmn 027a 199 plusmn 048a 128 plusmn 014bc 3311 plusmn 660ab 366 plusmn 98bc

C V CV 32 plusmn 015ab 198 plusmn 036a 121 plusmn 009c 3965 plusmn 658ab 207 plusmn 43a

C B CB 323 plusmn 017ab 156 plusmn 041a 141 plusmn 030c 3987 plusmn 840ab 362 plusmn 97bc

C Bm CBm 348 plusmn 033b 172 plusmn 036a 156 plusmn 044c 4149 plusmn 740a 311 plusmn 52abc

A N AN 303 plusmn 011a 176 plusmn 004a 063 plusmn 013a 2568 plusmn 901b 386 plusmn 23c

A V AV 336 plusmn 019b 215 plusmn 030ab 113 plusmn 012bc 3534 plusmn 260b 313 plusmn 56abc

A B AB 304 plusmn 021a 217 plusmn 053b 111 plusmn 024bc 4199 plusmn 800a 260 plusmn 54ab

A Bm ABm 297 plusmn 033a 280 plusmn 036b 084 plusmn 017a 4189 plusmn 810a 202 plusmn 55a

CN control diet without additives CV V vanadium compounds with control diet CB B vanadium compounds with control diet CBm Bm vanadiumcompounds with control diet AN high-fat diet without additives AV V vanadium compounds with high-fat diet AB B vanadium compounds with high-fatdiet ABm Bm vanadium compounds with high-fat dietCa calcium TCHOL total cholesterol TG triglycerides HDL high-density lipoprotein PON1 activity of paraoxonase 1Means in the same columns followed by different letters (a b c) are significantly different at 119901 lt 005 according to Tukeyrsquos test

vanadium complex in control diet (CV) activity of PON 1significantly decreased (119901 lt 005) compared to control diet(CN) and B vanadium compounds with control diet (CB) Inother tested parameters like TCHOL TG and HDL we didnot note significant changes

In turn V vanadium complex with high-fat diet (AV)statistically increased (119901 lt 005) concentration of calciumcompared to other vanadium complexes as well as high-fatdiet (AB ABm and A) B as well as Bm complexes with high-fat diet (AB ABm) statistically increased (119901 lt 005) level ofTCHOL compared to high-fat diet (A) Opposite dependencefor these compounds was observed for activity of PON1 Ratsfed with high-fat diet in AB andABm groups had higher levelof HDL in plasma than AN or AV groups V as well as Bcomplexes with high-fat diet (AV AB) statistically increased(119901 lt 005) the level of TG compared to AN and ABm group

4 Discussion

The role of vanadium in the human body has not been fullyunderstood yetThis trace element is still subject of numerousbiochemical studies to understand its significance to humanhealth Recently vanadium is considered essential to lifePrevious studies were primarily related to its antidiabeticproperties [19 20] In animal models of diabetes types 1 and2 research was conducted mostly into vanadium complexeswith organic ligands for example bis(maltolato)oxidovana-dium(IV) bis(picolinato)oxidovanadium vanadyl acetylace-tone and vanadyl 3-ethylpentane-24-dione (Vet) [21 22]Organic complexes of vanadium seem to have stronger effectsand gain an advantage over inorganic salts as potentialantidiabetic agents What is more such complexes have notshown adverse effects on gastrointestinal tract Therefore inthis study we used organic complexes of vanadium(IV) (Band Bm complexes) and vanadium(V) (V complex) whichcontain a bipyridine as an organic ligand In addition bipyri-dine in Bm complex was substituted at position 4 by methylgroup The presence of additional group at heterocyclic ringof this complex contributed to increasing lipophilicity of itwhich may have importance for enhanced bioavailability In

our study we focused on assessing the organic vanadiumcomplex on lipid metabolism under conditions of high-fatdiet in nondiabetes animal model due to the lack of suchresearch This was the main reason for our experiment

B and Bm complexes with high-fat diet statistically increased(119901 lt 005) the level of TCHOL One of the potential expla-nations for the increased value of this parameter would bethe fact that those compounds also significantly elevated (119901 lt005) the level of HDL However an important limitation ofour study was not to determine the level of LDL In rats fedwith control diet we did not note any changes induced by oneof vanadium complexes Similarly Majithiya et al observedthat vanadium complex like bis[curcumino]oxidovanadiumadjusted values of lipid parameters (decreased level ofTCHOL and TG) in streptozotocin induced diabetic ratswithout any impact on control nondiabetes rats [23] Pillaiaet al also noted no changes in the level of lipids parametersin nondiabetic rats receiving vanadium-3-hydroxy flavonecomplex In turn in diabetic rats the same compoundshowed antidyslipidemic properties [6]

In our study B and Bm complexes significantly increased(119901 lt 005) the level of HDL in combination with a high-fat diet Alike results were obtained among people exposedto vanadium compounds [24] as well as rabbits fed witha high-cholesterol diet supplemented with vanadium (assodium metavanadate) [25] Additionally Bm complex inhigh-fat diet as the only one of used organic complexes ofvanadium did not significantly increase the concentrationof TG These results encourage us to further research thisparticular compound Nevertheless it is possible too thathypolipidemic effect of different vanadium complexes isstrong in the presence of diabetes contrary to high supply ofsaturated fatty acids but without carbohydrate disorders

The consequence of oxidative stress is lowering of PON1activity as observed in the course of coronary artery disease[26] Therefore the attempt to regulate the activity of thisenzyme may seem particularly significant in treatment ofthis disease However in our studies B and Bm complexesof vanadium in conjunction with a high-fat diet caused astatistical decrease (119901 lt 005) in the activity of PON1 Further


V complex administered with control diet affected PON1 in asimilar way In turn Tas et al noted that vanadyl sulfate withstandard diet did not influence these parameters in healthyrats [26] The lack of significant difference in PON1 activitybetween AN and CN group seems to be quite puzzlingNevertheless in the studies on the effect of fatty diet onPON1 there are discrepancies too for example Thomas-Moya et al noted a decrease in the activity of PON1 inanimals fed with a high-fat as well as hypercholesterolemicdiets [27] Kudchodkar et al observed that diet rich in fishoil significantly reduces while trioleate increases the activityof it In turn in tripalmitate fed rats no significant change ofactivity of this parameter was observed compared to controldiet [28] In a study on people Calabresi et al have noted asignificant increase in the activity of PON1 in patients withhyperlipidemia who received 120596-3 polyunsaturated fatty acidfor 8 weeks compared to the placebo group [29] Thereforethe results in these studies indicate how the type of fattyacids is an important factor in regulating the activity ofPON1 What is more the time of our experiment perhapswas too short to observe change in this parameter betweenAN andCN group Nevertheless the quite unexpected resultsobtained by Kleemola et al are also worth noting whereactivity of PON negatively correlated with consumption offoods rich in antioxidants [30] This is another proof of thecomplexity of this issue and the necessity to further researchto understand the interaction between PON1 activity andspecific chemical or food component

5 Conclusions

In the present paper we have demonstrated that bis(441015840-dimethyl-221015840-bipyridine)oxidovanadium(IV) sulfate dehy-drate (Bm) compound is an interesting object to further studyas a potential candidate for controlling lipid metabolism incondition of high supply of fats althoughmolecular studies onthis particular compound are necessary to find out potentialintracellular mechanisms of diminish side effect of fat diet

Abbreviations

Compound V Sodium (221015840-bipyridine)oxidobisper-oxidovanadate(V) octahydrateNa[VO(O2)2(22

1015840-bpy)]sdot8H2OCompound B Bis(221015840-bipyridine)oxidovanadium(IV)

sulfate dihydrate[VO(SO4)(22

1015840-bpy)]sdot2H2OCompound Bm Bis(441015840-dimethyl-221015840-

bipyridine)oxidovanadium(IV) sulfatedihydrate[VO(441015840-Me-221015840-bpy)2]SO4sdot2H2O

GLUT-4 Glucose transporter type 4TCHOL Total cholesterolTG TriglyceridesHDL High density lipoproteinPON1 Paraoxonase 1

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

This work was supported by Higher Education in Polandstatutory activities DS-3600WIPiE2017 Faculty of Produc-tion and Power Engineering University of Agriculture inKrakow

References

[1] M Valko H Morris andM T D Cronin ldquoMetals toxicity andoxidative stressrdquoCurrentMedicinal Chemistry vol 12 no 10 pp1161ndash1208 2005

[2] Z-Y Zhang ldquoProtein tyrosine phosphatases prospects fortherapeuticsrdquo Current Opinion in Chemical Biology vol 5 no4 pp 416ndash423 2001

[3] M Z Mehdi S K Pandey J-F Theberge and A K SrivastavaldquoInsulin signal mimicry as a mechanism for the insulin-likeeffects of vanadiumrdquo Cell Biochemistry and Biophysics vol 44no 1 pp 73ndash81 2006

[4] M A Phanse M J Patil and K Abbulu ldquoSynthesis character-ization and evaluation of the suppression of insulin resistancein Type-II diabetes mellitus animals by treatment with metalcomplexrdquo Saudi Journal of Biological Sciences vol 23 no 3 pp420ndash425 2016

[5] A P Seale L A De Jesus M-C Park and Y-S Kim ldquoVana-dium and insulin increase adiponectin production in 3T3-L1adipocytesrdquo Pharmacological Research vol 54 no 1 pp 30ndash382006

[6] S I Pillaia S P Subramanianb and M KandaswamyaldquoAntidyslipidemic effect of a novel vanadium-3-hydroxy flavonecomplex instreptozotocin-induced experimental diabetes inratsrdquo Biomedicine Preventive Nutrition vol 4 no 2 pp 189ndash1932014

[7] S Barquera A Pedroza-Tobıas C Medina et al ldquoGlobaloverview of the epidemiology of atherosclerotic cardiovasculardiseaserdquoArchives ofMedical Research vol 46 no 5 pp 328ndash3382015

[8] M Zhao M T Cooney K Klipstein-Grobusch et al ldquoSimpli-fying the audit of risk factor recording and control a reportfrom an international study in 11 countriesrdquo European Journalof Preventive Cardiology vol 23 no 11 pp 1202ndash1210 2016

[9] D Litvinov H Mahini and M Garelnabi ldquoAntioxidant andanti-inflammatory role of paraoxonase 1 implication in arte-riosclerosis diseasesrdquo North American Journal of Medical Sci-ences vol 4 no 11 pp 523ndash532 2012

[10] M Wang X Lang S Cui et al ldquoQuantitative assessment of theinfluence of paraoxonase 1 activity and coronary heart diseaseriskrdquo DNA and Cell Biology vol 31 no 6 pp 975ndash982 2012

[11] Y Zhao Y Ma Y Fang et al ldquoAssociation between PON1activity and coronary heart disease risk a meta-analysis basedon 43 studiesrdquoMolecular Genetics and Metabolism vol 105 no1 pp 141ndash148 2012

[12] D M Shih L Gu S Hama et al ldquoGenetic-dietary regulation ofserum paraoxonase expression and its role in atherogenesis ina mouse modelrdquo Journal of Clinical Investigation vol 97 no 7pp 1630ndash1639 1996


[13] W Przybylski R Grybos D Rehder et al ldquoRole of the alkalimetal ion and hydrogen bonds inM[VO(O2)2bpy] sdot nH2O (M=Li+ Na+ K+ and Rb+) and Cs[VO(O2)2bpy] sdotH2O2 complexesthe X-ray crystal structures and spectroscopic propertiesrdquoPolyhedron vol 28 no 8 pp 1429ndash1436 2009

[14] M Krosniak M Gawlik and R Grybos ldquoEffect of vana-dium complexes and insulin administered simultaneously foroxidative stress in STZ diabetic ratsrdquo Bulletin of the VeterinaryInstitute in Pulawy vol 53 no 3 pp 535ndash540 2009

[15] H W Eckerson J Romson C Wyte and B N La Du ldquoThehuman serum paraoxonase polymorphism identification ofphenotypes by their response to saltsrdquoThe American Journal ofHuman Genetics vol 35 no 2 pp 214ndash227 1983

[16] S Troncoso Skidmore and B Thompson ldquoBias and precisionof some classical ANOVA effect sizes when assumptions areviolatedrdquoBehavior ResearchMethods vol 45 no 2 pp 536ndash5462013

[17] J M Mahachie John F Van Lishout E S Gusareva and K VanSteen ldquoA robustness study of parametric and non-parametrictests in model-based multifactor dimensionality reduction forepistasis detectionrdquo BioData Mining vol 6 no 1 article 9 2013

[18] R Konig AMatysiakW Kordecki C Sieluzycki N Zachariasand P Heil ldquoAveraging auditory evoked magnetoencephalo-graphic and electroencephalographic responses a critical dis-cussionrdquo European Journal of Neuroscience vol 41 no 5 pp631ndash640 2015

[19] Y Shechter I Goldwaser M Mironchik M Fridkin and DGefel ldquoHistoric perspective and recent developments on theinsulin-like actions of vanadium toward developing vanadium-based drugs for diabetesrdquo Coordination Chemistry Reviews vol237 no 1-2 pp 3ndash11 2003

[20] S Bolkent S Bolkent R Yanardag and S Tunali ldquoProtectiveeffect of vanadyl sulfate on the pancreas of streptozotocin-induced diabetic ratsrdquo Diabetes Research and Clinical Practicevol 70 no 2 pp 103ndash109 2005

[21] A K Srivastava and M Z Mehdi ldquoInsulino-mimetic and anti-diabetic effects of vanadium compoundsrdquo Diabetic Medicinevol 22 no 1 pp 2ndash13 2005

[22] M Z Mehdi and A K Srivastava ldquoOrgano-vanadium com-pounds are potent activators of the protein kinase B signalingpathway and protein tyrosine phosphorylation mechanism ofinsulinomimesisrdquo Archives of Biochemistry and Biophysics vol440 no 2 pp 158ndash164 2005

[23] J B Majithiya R Balaraman R Giridhar and M R YadavldquoEffect of bis[curcumino]oxovanadium complex on non-diabetic and streptozotocin-induced diabetic ratsrdquo Journal ofTrace Elements in Medicine and Biology vol 18 no 3 pp 211ndash217 2005

[24] Y Zhang Q Zhang C Feng et al ldquoInfluence of vanadiumon serum lipid and lipoprotein profiles a population-basedstudy among vanadium exposed workersrdquo Lipids in Health andDisease vol 13 no 1 article 39 2014

[25] G Subrahmanyam K D Sankar K Ramalingam and P SBhanu ldquoHypolipidemic and anti-atherogenic effects of vana-dium in high-fat diet rabbitsrdquo Trace Elements and Electrolytesvol 30 no 3 pp 114ndash121 2013

[26] S Tas E Sarandol S Ziyanok-Ayvalik N Ocak Z Serdarand M Dirican ldquoVanadyl sulfate treatment improves oxidativestress and increases serum paraoxonase activity in streptozo-tocin-induced diabetic ratsrdquo Nutrition Research vol 26 no 12pp 670ndash676 2006

[27] E Thomas-Moya M Gianotti A M Proenza and I LladoldquoParaoxonase 1 response to a high-fat diet gender differencesin the factors involvedrdquoMolecular Medicine vol 13 no 3-4 pp203ndash209 2007

[28] B J Kudchodkar A G Lacko L Dory and T V FungweldquoDietary fat modulates serum paraoxonase 1 activity in ratsrdquoJournal of Nutrition vol 130 no 10 pp 2427ndash2433 2000

[29] L Calabresi B Villa M Canavesi et al ldquoAn 120596-3 polyun-saturated fatty acid concentrate increases plasma high-densitylipoprotein 2 cholesterol and paraoxonase levels in patients withfamilial combined hyperlipidemiardquo Metabolism Clinical andExperimental vol 53 no 2 pp 153ndash158 2004

[30] P Kleemola R Freese M Jauhiainen R Pahlman G Alfthanand M Mutanen ldquoDietary determinants of serum paraoxonaseactivity in healthy humansrdquo Atherosclerosis vol 160 no 2 pp425ndash432 2002

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Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Paraoxonase 1 (PON1) is an enzyme involved in lipidmetabolism for example by limiting HDL and LDL oxi-dation Moreover this enzyme is also known for anti-inflammatory properties [9] Meta-analyses indicated a cor-relation between risk of cardiovascular disease and PON1activity among people independent of age or ethnicity [1011] On the other hand inadequate diet can contribute toreduction level of expression of that enzyme [12] Taking intoaccount a protective role of PON1 in cardiovascular diseaseswe found it also necessary to evaluate the influence of thesevanadium complexes on this parameter Because this enzymeis calcium-dependent we analyzed this element as well

2 Materials and Methods

21 Reagents The reagentswere purchased fromSigmaAldrichChemical Company (Steinheim Germany) and Avantor Per-formance Materials Poland SA

22 Synthesis of Vanadium Complexes In this study the fol-lowing complexes were used sodium (221015840-bipyridine)oxi-dobisperoxidovanadate(V) octahydrate Na[VO(O2)2(22

1015840-bpy)]sdot8H2O marked as V (4539 gmol) bis(221015840-bipyri-dine)oxidovanadium(IV) sulfate dihydrate [VO(SO4)(22

1015840-bpy)]sdot2H2O marked as B (51121 gmol) and bis(441015840-dimethyl-221015840-bipyridine)oxidovanadium(IV) sulfate dihy-drate [VO(441015840-Me-221015840-bpy)2]SO4sdot2H2O marked as Bm(56721 gmol) Synthesis of the first compoundVwas described[13] In turn synthesis of compound B was described [14] Incase of Bm compound process of synthesis was similar to Bcomplex except molar ratio of ligand to vanadium which was2 1 The purity of all analyzed complexes was confirmed bymicroanalysis and IR spectroscopy

23 Animals In the experiment male Wistar rats aged3 months and weighing 250 plusmn 15 g were divided into8 groups of 6 animals During the time of experiment(5 weeks) each group of animals was fed with differentdiet group CN standard diet (starchmdash62 caseinmdash20oilmdash50 calcium carbonatemdash28 Ca3(PO4)2mdash29lecithinmdash10 NaClmdash03 cellulosemdash47 minerals andvitamins mixmdash10 MgOmdash007 and K2SO4mdash023)group CV standard diet + vanadium complex V groupCB standard diet + vanadium complex B group CBmstandard diet + vanadium complex Bm group AN highfatty diet (starchmdash32 caseinmdash20 oilmdash50 lardmdash30calcium carbonatemdash28 Ca3(PO4)2mdash29 lecithinmdash10NaClmdash03 cellulosemdash47 minerals and vitaminsmixmdash10 MgOmdash007 and K2SO4mdash023) group AVhigh fatty diet + vanadium complex V group AB high fattydiet + vanadium complex B group ABm high fatty diet+ vanadium complex Bm In all vanadium treated groupstested complexes were administered by gavage once a dayduring 5 weeks in the dose of 20mgkg body mass

All animals had free access to feed and water and werekept in a room with a constant temperature of 23∘C and50ndash60 humidity with a 12-hour daynight cycle After 5weeks the animals were anesthetized This experience wasconducted with an approval of I Local Ethics Committee for

Animal Experiments of Jagiellonian University in Cracownumber 802009 17092009

24 Blood Preparation Blood samples were taken from aortainto heparinized tubes and then centrifuged (at 2500timesg for 15minutes at 4∘C) to obtain plasma which was kept frozen (atminus80∘C) until further analyses

25 Biochemical Parameters Biochemical analysis was doneusing standard biochemical analyzer Alize BioMerieux withstandard kits (Camdash61041 TCHOLmdash61218 TGmdash61236HDLmdash61001 and 61002) from BioMerieux Thus theobtained results were compared with Control Serum 1ODC0003 and Control Serum 2 ODC0004 (OLYMPUS)

26 Paraoxonase 1 Activity (PON1) in Plasma Paraoxonase1 (PON1) activity was determined by modified Eckersonmethod [15] A mixture of 025M Tris buffer (pH 8) and01M paraoxon in a volume ratio of 19 1 (vv) was addedto samples Then the absorbance was measured at 412 nmduring 2 minutes PON1 activity was estimated based onchanges in concentration of substrate

27 Statistical Analysis Weused two-way analysis of variance(ANOVA) in order to verify if the examined factors (explana-tory variables) influence the observed (dependent) variables[16] Before this we had checked if the main assumptionsconcerning normal distribution of dependent variable withingroups as well as homogeneity of variance were met [17]Normal distribution was verified by Shapiro-Wilk test whilehomogeneity of variancewas verified by Levenersquos test In turnBox-Cox transformationwas used for variables which did notmeet ANOVA assumptions [17 18]

Analysis of variance was conducted for each of the fol-lowing dependent variables Ca [mmoll] TCHOL [mmoll]TG [mmoll] HDL [mgdL] and PON1 [Umg protein]Intragroup factors were the type of diet (X1-diet) and typeof supplement (X2-supplement) Type of diet (X1-diet) had2 levels (C and A) in turn type of supplement (X2-supplement) had 4 levels (N B V and Bm)

Tukeyrsquos test was used to indicate homogeneous groups(marked by identical letters) All analyses were conducted atsignificance level 119901 = 005 Obtained data were statisticallyanalyzed using the STATISTICA (StatSoft Inc (2011) version10 httpwwwstatsoftcom)

Based on Levenersquos test 3 variables such as TCHOL[mmoll] TG [mmoll] and PON1 [Umg protein] did notmeet assumption of homogeneity of variance Thereforefor them Box-Cox transformation was made after whichvariablesmet the assumption concerning normal distribution(Shapiro-Wilk test) and homogeneity of variance (Levenersquostest) at significance level 119901 = 005 Then two-way analysisof variance (ANOVA) was used

3 Results

The results are summarized in Table 1 All parameters wereanalyzed in plasma of rats Bm vanadium complex in controldiet (CBm) statistically increased (119901 lt 005) concentrationof calcium compared to control diet (CN) In case of V














4 Discussion








5 Conclusions


Abbreviations









Acknowledgments


References





































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





























4 Discussion








5 Conclusions


Abbreviations









Acknowledgments


References





































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















5 Conclusions


Abbreviations









Acknowledgments


References





































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of








































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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