Sacha inchi odnosno Inka orah (Plukenetia volubilis Linneo) je drevna biljka, porijeklom iz Amazonske prašume, koja se sve više koristi u prehrani zbog njezine velike hranjive vrijednosti, a čiji se ...zdravstveni potencijal sve više prepoznaje. Različite su studije ispitale učinak konzumacije pojedinih sastojaka biljke, izoliranih iz sjemenki, lišća i ljuske, u prevenciji kardiovaskularnih bolesti, kroničnih upala, dermatitisa te kontroli proliferacije tumorskih stanica, naročito uzevši u obzir da je Inka orah bogat esencijalnim masnim kiselinama, fenolnim spojevima i vitaminom E, ima antioksidacijski, hipolipemični, imunomodulacijski i emolijentni učinak, te svojstvo uklanjanja teških metala iz vodenih otopina. Ovaj revijalni prikaz pruža detaljan opis svih dostupnih podataka o primjeni i biološkoj aktivnosti biljke P. volubilis L. koja se temelji na njezinom sadržaju esencijalnih lipida, što je potvrđeno dosadašnjom primjenom te biljke u zdravstvene svrhe, u prevenciji, terapiji i prehrani, te industrijskom primjenom, zbog čega predstavlja potencijalni izvor biološki aktivnih tvari.
Ferroptosis: regulated cell death Čepelak, Ivana; Dodig, Slavica; Dodig, Daniela Čepelak
Arhiv za higijenu rada i toksikologiju,
06/2020, Letnik:
71, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Ferroptosis is a recently identified form of regulated cell death that differs from other known forms of cell death morphologically, biochemically, and genetically. The main properties of ferroptosis ...are free redox-active iron and consequent iron-dependent peroxidation of polyunsaturated fatty acids in cell membrane phospholipids, which results in the accumulation of lipid-based reactive oxygen species due to loss of glutathione peroxidase 4 activity. Ferroptosis has increasingly been associated with neurodegenerative diseases, carcinogenesis, stroke, intracerebral haemorrhage, traumatic brain injury, and ischemia-reperfusion injury. It has also shown a significant therapeutic potential in the treatment of cancer and other diseases. This review summarises current knowledge about and the mechanisms that regulate ferroptosis.
Za održavanje fizioloških procesa sper- matogeneze i steroidogeneze u testisima te povoljnih mikorookolišnih uvjeta u tkivima epididimisa tijekom sazrijevanja, prolaska i pohrane spermija nužno je ...primjereno djelo- vanje antioksidansa radi održavanja fiziološ- ke razine reaktivnih kisikovih spojeva (ROS). Stanje oksidacijskog stresa, koje nastaje naru- šavanjem ravnoteže između oksidansa (ROS i dr.) i prooksidansa (antioksidansi) u korist ok- sidansa, može za posljedicu imati narušavanje spermatogeneze i steroidogeneze. Tkiva testisa i epididimisa sa spermijima različitog stupnja zrelosti podložna su lipidnoj peroksidaciji, od- nosno oksidacijskom stresu. Narušene funkcije testisa mogu se odraziti i na sposobnost stvara- nja gibljivih, vijabilnih i morfološki normalnih spermija koji imaju sposobnost oploditi jajne stanice te održati rast i razvoj zametka. Visoka je aktivnost antioksidacijskih enzima u testi- sima nužna za primjerenu zaštitu spermija i stanica tkiva testisa od oksidacijskih oštećenja. Nadalje, stjecanje gibljivosti i oplodne sposob- nosti spermija tijekom njihovog prolaska kroz epididimis povezano je s različitim biokemij- skim promjenama osobito u svojstvima njiho-
vih membrana. Tijekom prolaska kroz epidi- dimis spermiji su podvrgnuti stalnoj promjeni mikrookoliša u lumenu, koje je modificirano zbog sekrecijskih i endocitotičkih aktivnosti stanica sluznice epitela. U konačnici, usklađena aktivnost u sekreciji različitih tvari kao i endo- citozi u epitelnim stanicama duž kanala, utje- če na konačno sazrijevanje spermija, njihovu koncentraciju, zaštitu, pohranu i oplodnu spo- sobnost. Navedene uzastopne promjene prati i promjena osobitosti spermija tijekom njihovog prolaska kroz epididimis, a osobito promjene u svojstvima njihovih membrana. No, mijenja se i sastav bjelančevina, lipida i ostalih tvari u ra- zličitim dijelovima epididimisa, koje sudjeluju u procesima sazrijevanja spermija, a čije funk- cije nisu u potpunosti razjašnjene. Međutim, ni sposobnost testisa i epididimisa u zaštiti sper- mija od štetnih učinka oksidacijskih procesa koji se zbivaju tijekom njihove tvorbe, pohrane i sazrijevanja u epididimisima pomoću lokalno sintetiziranih antioksidansa, nije do sada u pot- punosti istražena.
The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue ...of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains.
The aim of this study was to investigate the oxidative and apoptotic potential of fluoxetine, a widely used antidepressant in Turkey and the world, and of its metabolite norfluoxetine on a model ...non-target organism,
to see how exposure to this group of antidepressants (specific serotonin reuptake inhibitors) could affect the aquatic environment in which they end up. Juvenile
specimens were chronically exposed to fluoxetine and norfluoxetine alone and in combination at concentrations found in the aquatic environment (0.091 and 0.011 μg/L, respectively) and to their 10-fold environmental concentrations for 21 days. Another group of 17-day-old animals were subacutely exposed to 100-fold environmental concentrations for four days. After exposure, we measured their glutathione peroxidase (GPx) and cholinesterase (ChE) activities, thiobarbituric acid-reactive substances (TBARS), and total protein content spectrophotometrically, while mitochondrial membrane potential (MMP) was analysed by fluorescence staining, and cytochrome c and ERK1/2 protein content by Western blotting. This is the first-time cytochrome c and ERK1/2 were determined at the protein level in
. We also measured their carapace length, width, and caudal spine length microscopically. At environmental concentrations fluoxetine and norfluoxetine caused an increase in ChE activity and brood production. They also caused a decrease in juvenile carapace length, width, and caudal spine length and depolarised the mitochondrial membrane. At 10-fold environmental concentrations, GPx activity, lipid peroxidation levels, cytochrome c, and ERK1/2 protein levels rose. The most pronounced effect was observed in
exposed to norfluoxetine. Norfluoxetine also decreased brood production. Similar effects were observed with subacute exposure to 100-fold environmental concentrations. However, total protein content decreased. All this confirms that fluoxetine and norfluoxetine have oxidative and apoptotic potential in
.
. have a great potential to give us precious insight into the mechanisms of environmental toxicants, but there is still a long way to go before they are clarified in these organisms.
Isoniazid is one of the most commonly used drugs to treat tuberculosis. Its administration is associated with a high incidence of hepatotoxicity. The aim of this study was to establish the protective ...effects of taurine against cytotoxicity induced by isoniazid and its suspected toxic metabolite hydrazine in isolated rat hepatocytes by measuring reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial depolarisation, reduced glutathione (GSH), and oxidised glutathione (GSSG). Isoniazid caused no significant ROS formation in normal hepatocytes, but in glutathione-depleted cells it was considerable. Hydrazine caused ROS formation and lipid peroxidation in both intact and glutathione-depleted cells. Both isoniazid and hydrazine caused mitochondrial membrane depolarisation. Hydrazine lowered cellular GSH reserve and increased GSSG. Taurine (200 μmol L
) and N-acetylcysteine (200 μmol L-1) effectively countered the toxic effects of isoniazid and/or hydrazine by decreasing ROS formation, lipid peroxidation, and mitochondrial damage. Taurine prevented depletion of GSH and lowered GSSG levels in hydrazine-treated cells. This study suggests that the protective effects of taurine against isoniazid and its intermediary metabolite hydrazine cytotoxicity in rat hepatocytes could be attributed to antioxidative action.
Izoniazid je jedan od najčešćih lijekova za tuberkulozu, ali se njegova primjena povezuje s veoma učestalom hepatotoksičnosti. Cilj je ovog istraživanja bio ocijeniti djelotvornost taurina u zaštiti izoliranih hepatocita štakora od citotoksičnosti izazvane izoniazidom i njegovim toksičnim metabolitom hidrazinom. U tu smo svrhu utvrdili razine reaktivnih kisikovih spojeva (ROS), lipidnu peroksidaciju, depolarizaciju mitohondrija, reducirani glutation (GSH) te oksidirani glutation (GSSG). Izoniazid nije doveo do značajnoga nastanka ROS-a u normalnih hepatocita, ali je zato bio značajan u stanica osiromašenih glutationom. I izoniazid i hidrazine doveli su do depolarizacije membrane mitohondrija. Hidrazin je smanjio staničnu rezervu GSH i povećao razinu GSSG. Taurin (200 μmol L-1) i N-acetilcistein (200 μmol L
) uspješno su zaštitili od toksičnoga djelovanja izoniazida i/ili hidrazina, smanjivši nastanak ROS-a, lipidnu peroksidaciju i oštećenje mitohondrija. Taurin je spriječio potpuni gubitak GSH-a te snizio razine GSSG-a u stanica tretiranih hidrazinom. Rezultati našeg istraživanje upućuju na to da se zaštitno djelovanje taurina od stanične toksičnosti izoniazida i hidrazina može pripisati njegovu andioksidacijskome djelovanju.
Asthma is a chronic disorder of the airways. Oxidative stress is an important part of asthma pathogenesis. It plays a crucial role in exacerbating the disease, as well as an important consequence of ...airways inflammation.
Aim: The present study was undertaken to investigate the lipid peroxidation and catalase activity in serum and antioxidant level in plasma of asthmatic patients and their association with lifestyle and severity of the disease.
Methods: A total of 210 subjects, 120 asthmatics and 90 healthy controls matched in respect to age, sex, lifestyle and socioeconomic status, were chosen randomly for the present study. The samples were analyzed for MDA concentration and catalase activity in serum and ferric reducing ability of plasma (FRAP). Statistical analysis was done using unpaired Student’s t-test, ANOVA with Duncan post hoc test and Pearson coefficient of correlation.
Results: The serum MDA was found to be significantly higher in the asthmatics as compared to healthy individuals (p<0.01) while catalase activity in serum and antioxidant level of the plasma were markedly lower in the asthmatics as compared to healthy individuals (p<0.01). A significant difference was observed in serum MDA, catalase activity and plasma antioxidant level among the patients in relation to the severity of disease. There was a marked increase in the serum MDA in the patients with longer duration of the disease (p<0.05).
Conclusion: The oxidant-antioxidant imbalance occurs in asthma leading to oxidative stress and is an important part of the asthma pathogenesis.
Uvod: Astma je hronično oboljenje disajnih puteva. Oksi- dativni stres čini važan deo u patogenezi astme. Ima presudnu ulogu u pogoršanju bolesti i predstavlja važnu posle- dicu upale disajnih puteva.
Ova studija je preduzeta kako bi se istražili lipidna peroksi- dacija i aktivnost katalaze u serumu i nivo antioksidanasa u plazmi kod bolesnika sa astmom i njihova povezanost sa životnim stilom i težinom bolesti.
Metode: Ukupno 210 ispitanika, 12|0 astmatičara i 90 zdravih kontrolnih ispitanika odgovarajuće starosti, pola, životnog stila i socioekonomskog statusa, nasumično je izabrano za ovu studiju. Analizom uzoraka određene su koncentracija MDA i aktivnost katalaze u serumu i primenjena je metoda FRAP (ferric reducing ability of plasma). Statistička analiza je izvršena pomoću Studentovog t testa, testa ANOVA sa Duncan post hoc testom i Pearsonove korelacije koeficijenta.
Rezultati: MDA u serumu bio je značajno viši kod astmatičara u poređenju sa zdravim ispitanicima (p<0,01), dok su aktivnost katalaze u serumu i nivo antioksidanasa u plazmi bili upadljivo niži kod astmatičara u poređenju sa zdravim ispitanicima (p<0,01). Između pacijenata je uočena značajna razlika u nivoima MDA u serumu, aktivnosti katalaze i nivoima antioksidanasa u plazmi u odnosu na težinu oboljenja. Postojao je upadljiv porast nivoa MDA u serumu kod pacijenata povezan sa dužinom bolesti (p<0,05).
Zaključak: U astmi se javlja poremećaj oksidantne-antiok- sidantne ravnoteže, što dovodi do oksidativnog stresa i čini važan deo patogeneze astme.
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.
Izloženost kadmiju neizbježna je zbog njegove sveprisutnosti u okolišu kao prirodne sastavnice Zemljine kore i kao onečišćenja. Kadmij može izazvati toksične učinke u gotovo cijelom organizmu ...vezanjem za biološke strukture i nakupljanjem u tkivima, poticanjem stvaranja slobodnih radikala, kao i međudjelovanjem s esencijalnim elementima, često u obliku antagonizma. S druge strane, dodatnim unosom esencijalnih elemenata može se utjecati na raspodjelu i štetne učinke kadmija. Selenij je esencijalan mikroelement i
antioksidans, a zbog svojstva vezanja za kadmij (kao i živu, arsen i druge toksične elemente) te uloge u detoksifi kaciji, detaljnije se počelo istraživati međudjelovanje kadmija i selenija. U radu je dan pregled dosadašnjih saznanja o toksikokinetici i toksikodinamici kadmija, biokinetici i biodinamici selenija i mehanizmima njihova međudjelovanja proizašlih uglavnom iz istraživanja na životinjama i ograničenu broju istraživanja u ljudima. Različite doze i odnos doza, način i dužina izloženosti kadmiju i seleniju u pokusima na životinjama uzrok su često vrlo oprečnih rezultata istraživanja opisanih u literaturi. Buduća istraživanja međudjelovanja kadmija i selenija treba usmjeriti na osjetljive skupine stanovništva i na
istraživanje mehanizama tog međudjelovanja. Doze i izloženost u pokusima na životinjama treba prilagoditi dugotrajnim i niskim razinama izloženosti koje su najčešće u ljudi.
Twelve new 4-(1H-indol-3-yl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-2-ones/thiones (7-18) have been synthesized by reacting 1-aryl-3-(1H-indol-3-yl)-2-propen-1-one with urea and thiourea in ethanolic ...potassium hydroxide. Their structures have been confirmed by IR, 1H NMR and mass spectral data. The compounds were tested for their anti-inflammatory activity. Test results revealed that compounds showed 49.5 to 70.7% anti-inflammatory activity where-as the standard drug ibuprofen showed 86.4% activity at the same oral dose. Four compounds, 4-(1H-indol-3-yl)-6-(4-chlorophenyl)-1,2,3,4-tetrahydropyrimidin-2-one (8), 4-(1H-indol-3-yl)-6-(4-methylphenyl)-1,2,3,4-tetrahydropyrimidin-2-one (10), 4-(1H-indol-3-yl)-6-(4-chlorophenyl)-1,2,3,4-tetrahydropyrimidin-2-thione (14), 4-(1H-indol-3-yl)-6-(4-methylphenyl)-1,2,3,4-tetrahydropyrimidin-2-thione (16), that showed significant anti-inflammatory activity were selected to study their ulcerogenic and lipid peroxidation activities. All tested compounds showed significant reduction in the ulcerogenic potential and lipid peroxidation compared to the standard drug ibuprofen.
Dvanaest novih 4-(1H-indol-3-il)-6-fenil-1,2,3,4-tetrahidropirimidin-2-ona/tiona (7-18) sintetizirano je reakcijom 1-aril-3-(1H-indol-3-il)-2-propen-1-ona s ureom i tioureom u etanolnoj otopini kalijeva hidroksida. Njihove strukture potvrđene su IR, 1H NMR i masenom spektrometrijom. Farmakološko vrednovanje pokazalo je da ti spojevi imaju od 49,5 do 70,7% protuupalnog djelovanja, dok je standardni lijek ibuprofen pokazao 86,4% djelovanja uz istu peroralno uzetu dozu. Spojevi koji pokazuju značajno protuupalno djelovanje (8, 10, 14, 16) ispitani su na ulcerogenost i djelovanje na lipidnu peroksidaciju. Svi testirani spojevi su značajno manje ulcerogeni i manje djeluju na lipidnu peroksidaciju od ibuprofena.
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