Glutationilacija – regulacijska uloga glutationa u fiziološkim procesima

Glutathione (γ-glutamyl-cysteinyl-glycine) is an intracellular thiol molecule and a potent antioxidant that participates in the toxic metabolism phase II biotransformation of xenobiotics. It can bind to a variety of proteins in a process known as glutathionylation. Protein glutathionylation is now recognised as one of important posttranslational regulatory mechanisms in cell and tissue physiology. Direct and indirect regulatory roles in physiological processes include glutathionylation of major transcriptional factors, eicosanoids, cytokines, and nitric oxide (NO). This review looks into these regulatory mechanisms through examples of glutathione regulation in apoptosis, vascularisation, metabolic processes, mitochondrial integrity, immune system, and neural physiology. The focus is on the physiological roles of glutathione beyond biotransformational metabolism.Glutation (γ-glutamil-cisteinil-glicin) stanični je tripeptid, tiolni spoj i jaki antioksidans koji sudjeluje u metabolizmu otrova i biotransformaciji ksenobiotika faze II. Može se vezati na različite proteine u procesu poznatom pod nazivom glutationilacija. Proteinska glutationilacija dokazano je jedan od važnih posttranslacijskih upravljačkih mehanizama u fiziologiji stanica i tkiva. Izravne i neizravne upravljačke uloge u fiziološkim procesima uključuju glutationilaciju glavnih transkripcijskih faktora, eikozanoida, citokina i dušikova oksida (NO). U ovom se preglednom radu razmatraju navedeni upravljački mehanizmi na primjerima regulacije glutationom u apoptozi, vaskularizaciji, metaboličkim procesima, mitohondrijskom integritetu, imunološkom sustavu i fiziologiji živčanog sustava. Težište je rada na novim opisanim fiziološkim ulogama glutationa, pored uobičajeno opisane uloge u biotransformacijskom metabolizmu

The Dual Nature of the Antiepileptic Drug Valproic Acid, With Possible Beneficial Effects in Alzheimer’s Disease

Valproic acid (VPA) is a short fatty acid with strong anticonvulsant properties. It has diverse effects in different tissues with opposing mechanisms of physiological action. Due to the effects on energy, fatty acid, and cholesterol metabolism, it may be a risk factor for the development of diabetes with its associated complications of atherosclerosis, weight gain, hypertension, insulin resistance and other complications. Its negative effects on the endocrine system can have severe health consequences, especially in the female population.VPA produces proinflammatory and proapoptotic effects in the liver and anti-inflammatory and antiapoptotic effects in the central nervous system. It also causes abnormalities in lipid and cholesterol transport in the liver and the reproductive organs, while in neural stem cells it decreases cholesterol accumulation and helps neural growth and differentiation. However, in the CNS it has some beneficial effects which are proposed to be important in Alzheimer’s disease (AD). In AD mouse models, VPA exerted antiapoptotic effects and the expression of transcription factors that promote neurite growth. Most of the adverse pathogenic actions or beneficial molecular effects are not fully understood. We present an overview and comparison of the different properties of VPA and their effects on estrogen and cholesterol metabolism, lipid transport, Alzheimer’s disease, and on the physiology of the liver, reproductive organs, and neuronsfrom in vitro and in vivo (in animal models and patients) studies

BIOLOŠKE ZNAČAJKE TUROPOLJSKE PASMINE SVINJA KAO ČIMBENICI OBNOVE I OČUVANJA POPULACIJE

Since 1996, Turopolje pig breed, an autochthonous Croatian breed and one of the older European pig breed is in the state of renewal and conservation. The aim of this study was to determine the size of breeding and effective (Ne) population and some of the biological traits which should be of importance in the program of in-situ preservation. According to the FAO standards, this breed is in the status of critical/endangerment although the obtained results showed the increase of breeding (12 vs. 130 sows and 3 vs. 15 boars) and effective population (9.6 vs. 53.8) from 1996 to 2008, respectively. The average litter size (number of born piglets in total and live were 7.7 and 6.3, respectively) and piglets weights at 1st (1.25 kg) and 42nd (4.4 kg) day of age were within the standards for this breed. The average survival of piglets from 1st to 42nd day of age was 73.5%. The composition of carcass and carcass parts estimated as a ratio of muscle:fat tissues was 1.1:1.0 and 0.8-1.5:1.0, respectively. In addition, fatty acid composition of M. longissimus dorsi (MLD) and back fat as well as MLD histochemical and histomorphological characteristics (diameter and proportion of red slow-twitch oxidative (SO), white fast-twitch glycolytic (FG) and intermediate fast-twitch oxidative glycolytic (FOG) fibre types) were specific. The characteristics of carcass and tissues traits are consequences of specific historical conditions, breeding, selection and production in specific environment. The biological traits of Turopolje pig breed are not limiting factors in the increasing of breeding population and changing of the present endangerment status.Turopoljska pasmina svinja – autohtona hrvatska pasmina i jedna od starijih pasmina svinja u Europi je u statusu obnove i zaštite od 1996 godine. Cilj rada je utvrditi veličinu uzgojne i efektivne ( Ne) populacije kao i neka biološka svojstva koja su od važnosti za provođenje in situ programa očuvanja pasmine. Prema FAO standardima o veličini populacija životinja koje su u nestajanju, ova pasmina je u statusu kritične ugroženosti iako broj za 1996 i 2008 pokazuju povećanje populacije kako uzgojne (krmača 12 i 138; nerasta 3 i 15), tako i Ne (9.6 i 53,8). Prosječne vrijednosti za svojstva, veličina legla (ukupno 7,7 i živo 6,3 oprasene prasadi) i mase prasadi 1. i 42. dan starosti (1,25 kg i 4,4 kg) su u granicama standarda za ovu pasminu. Preživljavanje prasadi od 1. do 42. dan života je 73,5%. U radu je analiziran sastav trupa i pojedinih dijelova, a omjeri mišićnog i masnog tkiva u trupu i dijelovima bili su 1,1:1 i 0,8-1,5:1,0. Sastav masnih kiselina utvrđen u mišiću Longissimus dorsi (MLD) i leđnoj slanini (pozicija 13./14. rebro) kao i histokemijska i histomorfološka svojstva mišićnih vlakana MLD, crvena (red slow-twitch oxidative, SO), bijela (white fast-twitch glycolytic, FG) i srednja (intermediate fast-twitch oxidative glycolytic, (FOG) su specifični kod ove pasmine u odnosu na neke druge. Značajke trupa i tkiva posljedica su specifičnih povijesnih uvjeta uzgoja, selekcije i tehnologija proizvodnje otvorenog sustava u specifičnom okolišu. Biološke značajke Turopoljske svinje/pasmine nisu ograničavajući čimbenici povećanju uzgojne populacije i mijenjanja sadašnjeg statusa ugroženosti od nestajanja

Influence of Dietary Treatment on Lipid Metabolism in Metabolic Syndrome

The metabolic syndrome is a very common disease associated with an increased risk of type 2 diabetes mellitus and cardiovascular disease. Disturbed lipoprotein metabolism characterized by elevated TAG, low HDL-cholesterol concentrations and insulin-resistance are the key features of the metabolic syndrome. Nutrition, especially the quality of dietary fat, plays an important role in the development and progression of the metabolic syndrome through infl uence on the expression of the gene encoding key regulatory enzymes of lipid and glucose metabolism. Dietary ω-6 and ω-3 PUFA reduce triglyceride accumulation in skeletal muscle, suppress hepatic lipogenesis, reduce hepatic triglyceride output and induce fatty acid oxidation in both liver and skeletal muscle, resulting in improvements of the metabolic syndrome. Genetic variation that predisposes to metabolic disturbances could interact with diet, modulating individual susceptibility to developing these conditions. Individuals with a ˝sensitive genotype˝ will be most susceptible to the impact of dietary therapy in order to reduce the risk of the metabolic syndrom

What is Nutrigenomics?

Uspjehom projekta sekvencioniranja ljudskog genoma, povećalo se razumijevanje uzroka, a time i prevencije različitih bolesti u ljudi. Spoznalo se da mijenjajući prehrambene navike možemo spriječiti pojavu nekih bolesti. Tako se na području istraživanja prehrane razvija nova disciplina, nutrigenomika. Taj novi smjer molekularne prehrane omogućuje upoznavanje pozadine interakcije hrane koju konzumiramo i našeg genetičkog profi la, a time nam daje i mogućnost razvoja novih načina liječenja i prevencije bolesti. U ovom radu opisani su osnovni ciljevi i metode nutrigenomike te njena praktična primjena u razvoju koncepta individualne prehraneThe success of sequencing the human genome has led to the increasing understanding of causes and thus the prevention of various human illnesses. It is understood that by adjusting ones dieting habits one can prevent disease appearance. Such knowledge has made way for a new discipline in the fi eld of nutrition research, nutrigenomics. This novel direction of molecular nutrition provides insight into the interaction of the food we consume and our genetic profi le, and therefore grants the possibility to develop new methods of treatment and disease prevention. This article encloses the description of the primary objective and the methods of nutrigenomics as well as its practical implementation in the development of an individual diet concept

The Effects of Olive and Pumpkin Seed Oil on Serum Lipid Concentrations

Low-fat diets increase serum triacilglycerol and decrease HDL-cholesterol concentrations, thereby potentially adversely affecting cardiovascular disease (CVD) risk. The present study compared the CVD risk profi le of a high-MUFA diets (olive oil) and high-PUFA diets (pumpkin seed oil). The most signifi cant difference between the two groups was that the atherogenic index in groups given olive oil was significantly lower (for approximately 60 %) than atherogenic index recorded in control group, while in the group receiving pumpkin seed oil this reduction was approximately 40 %. Collectively, these fi ndings point to the fact that both a high MUFA and PUFA diet may be preferable to a low-fat diet because of more favorable effects on the CVD risk profile

Polifenoli iz vinskog taloga kao nove funkcionalne bioaktivne tvari za prevenciju oksidacijskog stresa i hiperlipidemije

The study examines the potential of wine industry by-product, the lees, as a rich mixture of natural polyphenols, and its physiological potential to reduce postprandial metabolic and oxidative stress caused by a cholesterol-rich diet in in vivo model. Chemical analysis of wine lees showed that their total solid content was 94.2 %. Wine lees contained total phenols, total nonflavonoids and total flavonoids expressed in mg of gallic acid equivalents per 100 g of dry mass: 2316.6±37.9, 1332.5±51.1 and 984.1±28.2, respectively. The content of total anthocyanins expressed in mg of cyanidin-3-glucoside equivalents per 100 g of dry mass was 383.1±21.6. Antioxidant capacity of wine lees determined by the DPPH and FRAP methods and expressed in mM of Trolox equivalents per 100 g was 259.8±1.8 and 45.7±1.05, respectively. The experiment lasted 60 days using C57BL/6 mice divided in four groups: group 1 was fed normal diet and used as control, group 2 was fed normal diet with added wine lees, group 3 was fed high-cholesterol diet (HCD), i.e. normal diet with the addition of sunflower oil, and group 4 was fed HCD with wine lees. HCD increased serum total cholesterol (TC) by 2.3-fold, triacylglycerol (TAG) by 1.5-fold, low-density lipoprotein (LDL) by 3.5-fold and liver malondialdehyde (MDA) by 50 %, and reduced liver superoxide dismutase (SOD) by 50 %, catalase (CAT) by 30 % and glutathione (GSH) by 17.5 % compared to control. Conversely, treatment with HCD and wine lees reduced TC and LDL up to 1.4 times more than with HCD only, with depletion of lipid peroxidation (MDA) and restoration of SOD and CAT activities in liver, approximating values of the control. HDL levels were unaffected in any group. Serum transaminase activity showed no hepatotoxic properties in the treatment with lees alone. In the proposed model, wine lees as a rich polyphenol source could be a basis for functional food products without alcohol.U radu je istražena moguća uporaba vinskog taloga, polifenolima bogatog otpadnog proizvoda u industriji vina, u prehrani i ispitan je njegov fiziološki učinak na smanjenje oksidacijskog stresa uzrokovanog konzumacijom hrane bogate kolesterolom na modelu in vivo. Kemijskom je analizom utvrđeno da je udjel čvrste tvari u vinskom talogu bio 94,2 %; ukupnih fenola 2316,6±37,9; neflavonoida 1332,5±51,1 i flavonoida 984,1±28,2 mg u 100 g suhe tvari, izražen kao ekvivalent galne kiseline. Udjel ukupnih antocijana bio je 383,11±21,6 mg u 100 g suhe tvari, izražen kao ekvivalent cijanidin-3-glukozida. Ukupni antioksidacijski potencijal određen pomoću metode DPPH bio je (259,8±1,8) mM Trolox ekvivalenta u 100 g suhe tvari, a pomoću metode FRAP (45,7±1,05) mM u 100 g suhe tvari. Kvalitativni udjel polifenola određen je HPLC-om. Miševi C57/Bl6 hranjeni su tijekom 60 dana jednim od tipova prehrane: (i) normalnom hranom (kontrolna skupina), (ii) hranom s dodatkom ekstrakta vinskog taloga (1 g suhe tvari po kg po danu), (iii) hranom s velikim udjelom kolesterola (2 % kolesterola u 2 mL ulja po životinji po danu), i (iv) hranom bogatom kolesterolom (kao skupina 3) s dodatkom ekstrakta vinskog taloga (kao skupina 2). Kolesterolom bogata ishrana povećala je (p<0,05) razinu ukupnog kolesterola u serumu za 2,3; triacilglicerida za 1,5; LDL kolesterola za 3,5 puta, zatim je povećala razinu malondialdehida u jetri (p<0,05) i reducirala aktivnost superoksid dismutaze za 50 %, katalaze za 30 % i glutationa za 17,5 % u odnosu na kontrolni uzorak. Ishrana bogata kolesterolom s dodatkom ekstrakta vinskog taloga smanjila je (p<0,05) razinu ukupnog i LDL kolesterola za 1,4 puta u odnosu na skupinu hranjenu hranom bogatom kolesterolom, uz smanjenje (p<0,05) razine lipidne peroksidacije (malondialdehida) i aktiviranje superoksid dismutaze i katalaze u jetri, s vrijednostima sličnim onima u kontrolnoj skupini. Vrijednosti HDL kolesterola nisu se mijenjale. Serumska aktivnost transaminaza nije pokazala hepatotoksičnost izolata vinskog taloga. U predloženom je eksperimentalnom modelu utvrđeno da je vinski talog bogat izvor polifenola, te da se može upotrijebiti za proizvodnju funkcionalne hrane bez alkohola

Primjena alkalnog kometnog testa u istraživanju radioprotektivnih učinaka alkoholnog ekstrakta propolisa i kvercetina na miševima ozračenim gama-zračenjem

The aim of this study was to assess radioprotective effects of quercetin and the ethanolic extract of propolis (EEP) in CBA mice exposed to a single radiation dose 4 Gy (60Co). The mice were treated with 100 mg kg-1 quercetin or EEP a day for three consecutive days either before (pre-treatment) or after gamma-irradiation (therapy). Leukocyte count was determined in blood drawn from the tail vein, and DNA damage in leukocytes was assessed using the alkaline comet assay. Genotoxic effects of the test compunds were also evaluated in non-irradiated mice. The levels of radioprotection provided by both test compounds were compared with those established in mice that were given chemical radioprotector S-(2-Aminoethyl)isothiouronium bromide hydrobromide (AET). Mice that received pre-treatment were less sensitive to irradiation. Mice given the post-irradiation therapy showed a slight but not significant increase in total leukocyte count over irradiated negative control. Quercetin showed better protective properties than EEP in both pre-treatment and therapy, and activated a higher number of leukocytes in non-irradiated mice. The alkaline comet assay suggests that both natural compounds, especially when given as pre-treatment, protect against primary leukocyte DNA damage in mice. At tested concentrations, EEP and quercetin were not genotoxic to non-irradiated mice. AET, however, caused a slight but not significant increase in DNA damage. Although the results of this study show the radioprotective potential of the test compounds, further investigation is needed to clarify the underlying protection mechanisms.Na miševima soja CBA istraženi su radioprotektivni učinci alkoholnog ekstrakta propolisa (AEP) i flavonoida kvercetina primijenjenih u obliku predtretmana i terapije usporedo s izlaganjem gama-zračenju iz izvora 60Co, doze 4 Gy. Testirane tvari injicirane su miševima intraperitonealno u dozi od 100 mg kg-1 tijekom tri uzastopna dana. Nakon završetka pokusa u uzorcima krvi ozračenih miševa utvrđen je ukupni broj leukocita, a razina primarnih oštećenja u DNA izmjerena je primjenom alkalnog kometnog testa. Usporedo su istraženi i mogući genotoksični učinci testiranih tvari na neozračenim miševima. Razine radioprotekcije koju pružaju propolis i kvercetin uspoređene su sa sintetskim radioprotektorom AET-om (S-(2-aminoetil)izotiouronij bromid hidrobromid). Predtretman miševa bilo kojim oblikom radioprotektora pridonosi boljem odgovoru na zračenje. U miševa koji su primili radioprotektore u obliku terapije uočen je mali porast ukupnog broja leukocita u odnosu na ozračenu negativnu kontrolu. Kvercetin je pružio bolju zaštitu od zračenja nego AEP, i u predtretmanu i terapiji, a u neozračenih miševa potaknuo je oslobađanje većeg broja leukocita u odnosu na negativnu kontrolu. Rezultati istraživanja upućuju na to da propolis i njegove fl avonoidne sastavnice, osobito ako su primijenjene prije ozračivanja, mogu učinkovito zaštititi miševe od štetnih učinaka ionizirajućeg zračenja i smanjiti razinu primarnih oštećenja DNA u leukocitima. AEP i kvercetin u testiranim dozama nisu bili genotoksični, za razliku od AET-a koji je izazvao mali porast razine oštećenja DNA u leukocitima neozračenih miševa. Iako rezultati istraživanja upućuju na radioprotektivne učinke testiranih prirodnih spojeva, radi pojašnjenja pretpostavljenih mehanizama radioprotekcije potrebna su daljnja istraživanja

Združeni učinci valproata i naringina na antioksidacijske i serumske pokazatelje bubrežne funkcije u miševa soja C57BL6

Valproate is known to disturb the kidney function, and high doses or prolonged intake may cause serum ion imbalance, kidney tubular acidosis, proteinuria, hyperuricosuria, polyuria, polydipsia, and dehydration. The aim of this in vivo study was to see whether naringin would counter the adverse effects of high-dose valproate in C57Bl/6 mice and to which extent. As expected, valproate (150 mg/kg bw a day for 10 days) caused serum hyperkalaemia, more in male than female mice. Naringin reversed (25 mg/kg bw a day for 10 days) the hyperkalaemia and activated antioxidative defence mechanisms (mainly catalase and glutathione), again more efficiently in females. In males naringin combined with valproate was not as effective and even showed some prooxidative effects.Valproat je jedan od najčešće primjenjivanih antiepileptika, a poznato je da prouzročuje poremećenu funkciju proksimalnih bubrežnih tubula. Fiziološki poremećaji i nefrotoksični učinci u nekih bolesnika nakon visokih doza ili produljenog uzimanja valproata uključuju disbalans iona u serumu, bubrežnu tubularnu acidozu, proteinuriju, hiperurikozuriju, poliuriju, polidipsiju, dehidraciju i druge poremećaje. U okviru ovog eksperimentalnog rada primijenili smo visoke doze valproata i združeni tretman valproata i naringina u C57Bl/6 miševa. Naringin je poznati antioksidans i protuupalna flavonoidna molekula iz citrusnog voća. Cilj rada bio je utvrditi mogu li biološka svojstva naringina umanjiti štetne učinke na bubrege nakon tretmana valproatom. Valproat je in vivo prouzročio serumsku hiperkalijemiju, izraženiju u mužjaka nego u ženki miševa. Hiperkalijemija prouzročena valproatom bila je ublažena naringinom, a antioksidacijski obrambeni mehanizmi (uglavnom katalaza i smanjena glutationacija) bili su aktivirani, više u ženki. U mužjaka, zajednički tretman valproatom I naringinom nije bio tako učinkovit, a rezultati upućuju na moguće prooksidacijsko djelovanje u bubrežnom tkivu kada se obje tvari primjenjuju zajedno