Background: Human serum paraoxonase-1 (PON1) shows wide variation among different ethnic groups around the world. The aim of the present study was to determine the phenotype distribution and ...enzymatic activity of PON1 and ARE (arylesterase) in colorectal cancer (CRC), bladder cancer (BC) and multiple myeloma (MM) patients compared to healthy subjects.
Methods: A total of 160 subjects (40 CRC patients, 40 BC patients, 40 MM patients and 40 healthy controls) were admitted to the study. The phenotype distribution of PON1 was determined by using the dual substrate (paraoxon and phenylacetate) method.
Results: PON 1 and ARE activities were significantly lower in the cancer patients compared to the control group. The following phenotype distributions were assessed in the cancer and control groups: MM: 52.5% (QQ), 40% (QR), 7.5% (RR); CRC: 52.5% (QQ), 40% (QR), 7.5% (RR); BC: 55% (QQ), 35% (QR), 10% (RR); and controls: 40% (QQ), 57.5% (QR), 2.5% (RR).
Conclusions: We found that MM, CRC and BC patients were associated with lower PON1, ARE and stPON1 enzyme activities compared to the healthy subjects. However, PON1 phenotypes were similar between the cancer groups and control group.
Uvod: Humana serumska paraoksonaza-1 (PON-1) ispolja- va velike varijacije među različitim etničkim grupama širom sveta. Cilj ove studije bio je da se odrede fenotipska distribu- cija i enzimska aktivnost P0N1 i ARE (arilesteraze) kod paci- jenata sa kolorektalnim kancerom (KRK), kancerom bešike (KB) i multiplim mijelomom (MM) u poređenju sa zdravim ispitanicima.
Metode: Studijom je obuhvaćeno ukupno 160 ispitanika (40 pacijenata sa KRK, 40 sa KB, 40 sa MM i 40 zdravih osoba). Fenotipska distribucija PON1 određena je metodom dvostrukog supstrata (paraokson i fenilacetat).
Rezultati: Aktivnosti PON1 i ARE bile su značajno niže kod obolelih oa kancera u poređenju sa kontrolnom grupom. U grupama obolelih od kancera i kontrolnoj grupi utvrđene su sledeče fenotipske distribucije: MM: 52,5% (QQ), 40% (QR), 7,5% (RR); KRK: 52,5% (QQ), 40% (QR), 7,5% (RR); KB: 55% (QQ), 35% (QR), 10% (RR); i u kontrolnoj grupi: 40% (QQ), 57,5% (QR), 2,5% (RR).
Zaključak: Otkrili smo vezu između pacijenata sa MM, KRK i KB i nižih enzimskih aktivnosti PON1, ARE i stPONI nego kod zdravih ispitanika. Međutim, fenotipi PON1 bili su slični u grupama sa kancerom i kontrolnoj grupi.
This study investigated the effects of a nutritionally relevant intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids derived from oily fish or a fish oil supplement on selected ...cardiovascular risk factors in average middle-aged individuals.
Thirty-three participants were randomized to receive salmon (oily fish) providing 274 mg EPA + 671 mg DHA/day or a commercial fish oil supplement providing 396 mg EPA + 250 mg DHA/day in a cross-over trial over an 8-week period separated by a 6-month washout period. Blood samples were collected before and after each intervention and lipids, inflammatory and oxidative stress parameters were determined.
Plasma levels of EPA, DHA and total n-3 fatty acids significantly increased after both interventions. A decreasing trend in triglycerides was more pronounced with salmon than with the fish oil supplement, but the changes noticed were not significant. Although there were no relevant changes in inflammatory marker concentrations at the end of both interventions, significant negative correlations were noticed between total plasma n-3 fatty acids and soluble intercellular adhesion molecule and C-reactive protein throughout the whole intervention period (p<0.05). Among the oxidative stress parameters, intervention with salmon showed a prooxidative effect through a superoxide anion increase (p=0.025). A relevant positive correlation was also found between its concentration and total plasma n-3 fatty acids (p<0.05). Other oxidative stress markers were not significantly influenced by the dietary interventions applied.
Following two sets of recommendations for n-3 fatty acids intake aimed at the general public had only a moderate effect on the selected cardiovascular risk factors in average healthy middle-aged subjects over a short-term period.
The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we ...evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients.
The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-β-D-glucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage.
The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with TT genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients’ genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes’ activities.
Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug’s tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress.
Oxidative stress is thought to be a major contributor to complications during pregnancy, for example preeclampsia. However, reports regarding prooxidant-antioxidant balance in uncomplicated pregnancy ...are inconsistent. In this study, we aimed to compare the levels of oxidative stress in non-pregnant women with apparently normal pregnant women during the first trimester and at delivery.
An assay for the determination of prooxidant-antioxidant balance (PAB) was used in this study, in which the prooxidant burden and the antioxidant capacity were measured simultaneously in a single assay. The levels of oxidative stress were determined in 85 non-pregnant and 64 primigravid pregnant women.
Demographic data and biochemical indices did not differ significantly between the groups. Differences between PAB values were significant based on one-way ANOVA analysis (P<0.001). Using a post hoc test, we observed a statistically significant increase in PAB values during the first trimester and last trimester (P<0.001).
Normal pregnancy is associated with a change in the measure of redox status, as assessed by the PAB assay.
Veruje se da oksidativni stres u velikoj meri doprinosi komplikacijama u toku trudnoće, kao što je na primer preek- lampsija. Međutim, izveštaji o ravnoteži između prooksidanasa i antioksidanasa u trudnoći bez komplikacija se razlikuju. U ovoj studiji, cilj nam je bio da uporedimo nivoe oksidativnog stresa kod žena koje nisu trudne sa ženama u naizgled normal- noj trudnoći tokom prvog tromesečja i na porođaju.
U studiji je za određivanje ravnoteže prooksidansi/ antioksidansi (PAB) korišćen test u kom se istovremeno mere prooksidantni balast i antioksidantni kapacitet, u jednom testu. Nivoi oksidativnog stresa određeni su kod 85 žena koje nisu bile trudne i 64 trudnice u prvoj trudnoći.
Demografski podaci i biohemijski indeksi nisu se značajno razlikovali između grupa. Analiza ANOVA ukazala je na značajne razlike između vrednosti PAB (P<0,001). Pomoću post hoc testa uočili smo statistički značajan po- rast vrednosti PAB u toku prvog i poslednjeg tromesečja (P<0,001).
Normalna trudnoća povezana je s promenom u meri redoks statusa, utvrđenoj na osnovu PAB testa.
Elevated free radical production and/or insufficient antioxidative defense results in cellular oxidant stress responses. Sustained and/or intense oxidative insults can overcome cell defenses ...resulting in accumulated damage to macromolecules, leading to loss of cell function, membrane damage, and ultimately to cell death. Oxidative stress (OS) can result from conditions including excessive physical stress, exposure to environmental pollution and xenobiotics, and smoking. Oxidative stress, as a pathophysiological mechanism, has been linked to numerous pathologies, poisonings, and the ageing process. Reactive oxygen species and reactive nitrogen species, endogenously or exogenously produced, can readily attack all classes of macromolecules (proteins, DNA, unsaturated fatty acid). The disrupted oxidative-reductive milieu proceeds via lipid peroxidation, altered antioxidative enzyme activities and depletion of non-enzymatic endogenous antioxidants, several of which can de detected in the pre-symptomatic phase of many diseases. Therefore, they could represent markers of altered metabolic and physiological homeostasis. Accordingly, from the point of view of routine clinical-diagnostic practice, it would be valuable to routinely analyze OS status parameters to earlier recognize potential disease states and provide the basis for preventative advance treatment with appropriate medicines.
Povećano stvaranje slobodnih radikala i/ili nedovoljna antioksidativna zaštita dovodi do oksidativnog stresa (OS) u ćeliji. Produženi i/ili snažan oksidativni insult prevazilazi ćelijski antioksidativni odbrambreni kapacitet, dolazi do oštećenja makromolekula, gubi se ćelijska funkcija, oštećuju se membrane, što sve zajedno dovodi do smrti ćelije. Stanja organizma kao što su povećana fizička aktivnost, izloženost zagađenju čovekove okoline, ksenobioticima, pušenje itd. rezultiraju OS. Oksidativni stres, kao patofiziološki mehanizam, je potvrđen u brojnim patologijama, trovanjima i starenju. Reaktivne kiseonične vrste i reaktivne azotove vrste, endogenog ili egzogenog porekla, mogu lako da napadnu sve klase biomolekula (proteni, DNK, nezasićene masne kiseline). Narušen oksido-reduktivni milje, koji posreduje povećanju lipidne peroksidacije, promeni aktivnosti direktnih ili indirektnih antioksidativnih enzima, kao i smanjenom sadržaju neenzimskih antioksidanasa, može biti prepoznat u presimptomatskoj fazi brojnih bolesti. U tom smislu može biti pokazatelj izmenjenih metaboličkih i funkcionalnih zbivanja. U svakodnevnoj kliničko-dijagnostičkoj praksi analize parametara OS u biološkom materijalu bi trebalo da imaju svoje mesto, radi rane dijagnoze bolesti, prevencije i unapređivanja terapije.
Eicosanoids lead to the promotion of inflammation, cause fever and pain and have many other eff ects. NSAIDs block the action of cyclooxygenase (COX) during the process of converting arachidonic acid ...into inflammatory mediators, thus reducing the symptoms of inflammation. Investigations focusing on nonselective COX inhibitors, used in high doses, revealed harmful eff ects on myocardial function. Th e aim of our study was to assess the eff ects of two nonselective NSAIDs, diclofenac and ibuprofen, on cardiodynamic parameters, coronary flow and oxidative stress biomarkers in isolated rat hearts. Th e hearts of male Wistar albino rats were excised and retrogradely perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cm H
O). Th e experiments were performed under controlled conditions (Krebs-Henseleit physiological solution). Th e hearts were perfused with 10 μmol/l diclofenac and 10 μmol/l ibuprofen. Th e heart function parameters, including the maximum rate of pressure development (dp/dt max), minimum rate of pressure development (dp/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean perfusion pressure (MBP) and heart rate (HR), were continuously registered. Coronary flow (CF) was measured flowmetrically. Oxidative stress markers, including the index of lipid peroxidation measured as TBARS, nitric oxide measured through nitrites (NO
-), superoxide anion radical (O
-), and hydrogen peroxide (H
) in the coronary venous effluent, were assessed spectrophotometrically. Our results showed that diclofenac aff ected cardiodynamic parameters more significantly than did ibuprofen. Furthermore, the present data indicate that both estimated COX inhibitors do not promote the production of reactive oxygen species.
Eikosanoidi dovode do zapaljenja, uzrokuju groznicu i bol, i imaju mnoge druge efekte na organizam. NSAID onemogućavaju delovanje ciklooksigenaze (COX) u procesu konvertovanja arahidonske kiseline u medijatore zapaljenja, i na taj način smanjuju simptome zapaljenja. Istraživanja koja se bave primenom neselektivnih inhibitora COX, koji se koriste u visokim dozama, pokazala su njihove štetne efekte na funkciju miokarda. Cilj našeg istraživanja je bio da ispita efekte neselektivnih NSAID, diklofenaka i ibuprofena, na kardiodinamske parametre, koronarni protok i biomarkere oksidativnog stresa izolovanog srca pacova. Srca mužijaka Wistar albino pacova su uzimana i retrogradno perfundovana prema Langedorff -ovoj tehnici sa postepenim povećanjem perfuzionog pritiska (40-120 cm H
O). Eksperimenti su prvo izvođeni u kontrolnim uslovima (primena fiziološkog Krebs-Henseleit-ovog rastvora), nakon čega su srca perfundovana sa: 10 μmol/l dikolfenaka i 10 μmol/l ibuprofena. Parametri srčane funkcije koji su kontinuirano praćeni su: maksimalna stopa razvoja pritiska (dp/dt max), minimalna stopa razvoja pritiska (dp/dt min), sistolni pritisak u levoj komori (SLVP), dijastolni pritisak u levoj komori (DLVP), srednji perfuzioni pritisak (MBP) i frekvenca srčanog rada (HR). Koronarni protok (CF) je registrovan floumetrijski. Markeri oksidativnog stresa: indeks lipidne peroksidacije meren kao TBARS, azot-monoksid utvrđivan preko nitrata (NO
-), superoksid anjon radikal (O
-), i vodonik peroksid (H
) su mereni spektrofotometrijski u koronarnom venskom efluentu. Naši rezultati su pokazali da diklofenak ispoljava značajniji uticaj na kardiodinamske parametre u odnosu na ibuprofen. Pored toga, rezultati ove studije su pokazali da oba ispitivana inhibitora COX ne dovode po produkcije reaktivnih vrsta kiseonika.
Statins are potent cholesterol-lowering drugs that can have serious adverse effects on the muscles and liver. The aim of our in vitro study was to establish the protective effect of coenzyme Q
(CoQ
, ...in its optimal dose of 200 μmol L
) against cytotoxicity induced by atorvastatin, simvastatin, and lovastatin in isolated rat hepatocytes by observing parameters such as cell death, reactive oxygen species formation, lipid peroxidation, mitochondrial membrane potential, and cellular reduced and oxidised glutathione content. Our findings have shown that pretreatment with CoQ
was effective in reducing the toxic effects of statins in rat hepatocytes. This work demonstrates that the addition of CoQ
to statin treatment regimens may protect hepatocytes (and also other types of cells) from statin-induced injuries and alleviate their side effects.
Statini su snažni lijekovi za snižavanje kolesterola, koji mogu izazvati ozbiljne nuspojave u mišićima i jetrima. Svrha je ovog in vitro istraživanja bila utvrditi zaštitno djelovanje koenzima Q
(CoQ
, u optimalnoj dozi od 200 μmol L
) protiv citotoksičnosti atorvastatina, simvastatina i lovastatina u izoliranih štakorskih hepatocita kroz parametre poput vijabilnosti, nastanka reaktivnih kisikovih čestica, lipidne peroksidacije, potencijala mitohondrijske membrane te reduciranog i oksidiranog glutationa. Rezultati su pokazali da predtretman štakorskih hepatocita CoQ
djelotvorno ublažava toksične učinke statina te da bi njegovo kombiniranje sa statinima moglo zaštititi hepatocite (i druge vrste stanica) od oštećenja izazvanih statinima te ublažiti nuspojave povezane s ovim lijekovima.
Background: This study investigated the effects of a nutritionally relevant intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids derived from oily fish or a fish oil supplement on ...selected cardiovascular risk factors in average middle-aged individuals.
Methods: Thirty-three participants were randomized to receive salmon (oily fish) providing 274 mg EPA + 671 mg DHA/day or a commercial fish oil supplement providing 396 mg EPA + 250 mg DHA/day in a cross-over trial over an 8-week period separated by a 6-month washout period. Blood samples were collected before and after each intervention and lipids, inflammatory and oxidative stress parameters were determined.
Results: Plasma levels of EPA, DHA and total n-3 fatty acids significantly increased after both interventions. A decreasing trend in triglycerides was more pronounced with salmon than with the fish oil supplement, but the changes noticed were not significant. Although there were no relevant changes in inflammatory marker concentrations at the end of both interventions, significant negative correlations were noticed between total plasma n-3 fatty acids and soluble intercellular adhesion molecule and Creactive proteinconcenthroughout the whole intervention period (p<0.05). Among the oxidative stress parameters, intervention with salmon showed a prooxidative effect through a superoxide anion increase (p=0.025). A relevant positive correlation was also found between its concentration and total plasma n-3 fatty acids (p<0.05). Other oxidative stress markers were not significantly influenced by the dietary interventions applied.
Conclusion: Following two sets of recommendations for n- 3 fatty acids intake aimed at the general public had only a moderate effect on the selected cardiovascular risk factors in average healthy middle-aged subjects over a short-term period
Uvod: U ovoj studiji praćeni su efekti preporuka za unos eikozapentaenske (EPA) i dokozoheksaenske kiseline (DHA), iz dva razlicita izvora, lososa i suplementa sa ribljim uljem, na odabrane faktore kardiovaskularnog rizika u prosečnoj populaciji srednjih godina.
Metode: Trideset i tri ispitanika su po slučajnom izboru konzumirali losos koji je obezbeđivao 274 mg EPA +671 mg DHA/dan ili komercijalni suplement ribljeg ulja koji je obezbeđivao dnevno 396 mg EPA + 250 mg DHA tokom 8 nedelja. Nakon perioda od 6 meseci ispitanicima su zamenjene intervencije (ukrštena studija). Uzorci krvi su sakupljani pre i posle svake intervencije, a zatim su određivani lipidni, inflamatorni parametri kao i markeri oksidativnog stresa.
Rezultati: Koncentracije EPA, DHA i ukupnih n-3 masnih kiselina u plazmi su značajno povećane posle obe intervencije. Nije bilo statistički značajnnih promena u lipidnim parametrima, iako je zabelezeno vece smanjenje nivoa triglicerida posle intervencije lososom u poredenju sa suplementom. Nisu uočene značajne promene u koncentraciji inflamatornih markera, ali je utvrđena značajna negativna korelacija između ukupnih n-3 masnih kiselina plazme i rastvorljivog intracelularnog adhezionog molekula i C-reaktivnog proteina tokom ukupnog trajanja studije (p<0,05). Od parametara oksidativnog stresa, intervencija lososom je imala umeren prooksidativni efekat usled povecanja superoksidnog anjona (p= 0,025). Između ovog parametra i ukupnih n-3 masnih kiselina nađena je statistički značajna pozitivna korelacija. Ostali marked oksidativnog stresa nisu se značajno menjali.
Zaključak: Preporučene vrednosti za unos n-3 masnih kiselina pokazale su umeren efekat na parametre kardiovaskularnog rizika u prosečnoj populaciji srednjih godina u kratkom periodu trajanja studije
This work responds to the need to find, in a sole document, the affect of oxidative stress at different levels, as well as treatment with antioxidants to revert and diminish the damage. Oxidative ...Stress and Chronic Degenerative Diseases - a Role for Antioxidants is written for health professionals by researchers at diverse educative institutions (Mexico, Brazil, USA, Spain, Australia, and Slovenia). I would like to underscore that of the 19 chapters, 14 are by Mexican researchers, which demonstrates the commitment of Mexican institutions to academic life and to the prevention and treatment of chronic degenerative diseases.
Acetaminophen (N-acetyl para amino phenol, APAP) is a widely used antipyretic and analgesic drug responsible for various drug-induced liver injuries. This study evaluated APAP-induced toxicity in ...isolated rat hepatocytes alongside the protective effects of silafibrate and N-acetyl cysteine (NAC). Hepatocytes were isolated from male Sprague-Dawley rats by collagenase enzyme perfusion via the portal vein. This technique is based on liver perfusion with collagenase after removing calcium ions (Ca
) with a chelator. Cells were treated with different concentrations of APAP, silafibrate, and NAC. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial depolarisation were measured as toxicity markers. ROS formation and lipid peroxidation occurred after APAP administration to rat hepatocytes. APAP caused mitochondrial depolarisation in isolated cells
Administration of silafibrate (200 μmol L
) and/or NAC (200 μmol L
) reduced the ROS formation, lipid peroxidation, and mitochondrial depolarisation caused by APAP
Cytotoxicity induced by APAP in rat hepatocytes was mediated by oxidative stress. In addition, APAP seemed to target cellular mitochondria during hepatocyte damage. The protective properties of silafibrate and/or NAC against APAP‑induced hepatic injury may have involved the induction of antioxidant enzymes, protection against oxidative stress and inflammatory responses, and alteration in cellular glutathione content.
Acetaminofen (N-acetil-para-aminofenol, APAP) često je korišteni antipiretik i analgetik koji može izazvati oštećenja jetara. Na modelu izoliranih hepatocita štakora istražili smo toksične učinke APAP-a i protektivne učinke silafibrata i N-acetilcisteina (NAC). Hepatociti su izolirani iz mužjaka štakora soja Sprague-Dawley perfuzijom jetara i uvođenjem enzima kolagenaze putem portalne vene. Ta se tehnika zasniva na perfuziji jetara kolagenazom nakon uklanjanja kalcijevih iona (Ca
) kelatorom. Stanice su tretirane različitim koncentracijama APAP-a, silafibrata i NAC-a. Kao markeri toksičnosti mjereni su smrt stanica, stvaranje reaktivnih kisikovih vrsta (ROS), lipidna peroksidacija i depolarizacija mitohondrija. Primjena APAP-a u štakora izazvala je stvaranje ROS-ova i lipidnu peroksidaciju. APAP je uzrokovao depolarizaciju mitohondrija u izoliranim stanicama. Primjena silafibrata (200 μmol L
) i/ili NAC-a (200 μmol L
) smanjila je stvaranje ROS-a, lipidnu peroksidaciju i depolarizaciju mitohondrija uzrokovanu APAP-om. Utvrdili smo da je citotoksičnost APAP-a posredovana oksidativnim stresom. Nadalje, čini se da su mitohondriji ciljni stanični organeli za oštećenja hepatocita izazvanih APAP-om. Moguće je da su protektivna svojstva silafibrata i/ili NAC-a protiv APAP‑om induciranog oštećenja jetara uključivala i indukciju antioksidacijskih enzima, zaštitu od oksidativnog stresa i upalnih odgovora te promjenu razine staničnoga glutationa.
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