An imbalance in the redox homeostasis causes activation of multifaceted signaling responses which may be protective or deleterious. Amelioration of oxidative stress is one of the major modes of action of herbal supplements like Seabuckthorn (SBT). While the antioxidant potential of SBT is known, investigations into its effect on stress inducible signaling cascades are in progress. Here, we examine the impact of SBT on hypoxic tolerance and the mechanism behind its cardioprotective action. The efficacy of SBT was evaluated using the onset of gasping time (GT) at an altitude of 9754 m as the indicator for hypoxic tolerance. SBT led to a 100% increase in GT and curtailed hypoxia induced cardiac damage and free radical production. SBT upregulated HIF-1α and led to a two-fold increase in HO-1. A 100% increase in NO levels was observed. SBT reduced protein carbonylation and enhanced HSP70 levels. A statistically significant decline was seen in the markers of ER stress, GRP78, PERK and CHOP. SBT potentiated anti-inflammatory effects and downregulated NF-κB and TNF-α. Our study provides a novel insight into the mechanism behind the pro-survival effects of SBT against hypoxia, highlighting the cross talk between key adaptive responses mediated by HIF-1α and ER stress.
- MeSH
- antioxidancia terapeutické užití MeSH
- experimenty na zvířatech * MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa účinky léků MeSH
- financování organizované MeSH
- Hippophae * MeSH
- hypoxie MeSH
- kaspasy farmakologie MeSH
- laboratorní zvířata MeSH
- oxid dusnatý škodlivé účinky toxicita MeSH
- oxidační stres * účinky léků MeSH
- potkani Sprague-Dawley MeSH
- rostlinné přípravky terapeutické užití MeSH
- statistika jako téma MeSH
- volné radikály škodlivé účinky MeSH
- Check Tag
- mužské pohlaví MeSH
Leaf senescence is often associated with increased oxidative damage to cellular macromolecules by reactive oxygen species. However, very little is known about other radicals: gaseous free radical nitric oxide and related molecules--reactive nitrogen species. This review brings a short survey of the questions.
Přes pokroky v revaskularizační a podpůrné léčbě zůstává časná mortalita na kardiogenní šok komplikující akutní infarkt myokardu vysoká. V jedné pětině případů dochází v průběhu kardiogenního šoku k aktivaci systémové zánětlivé odpovědi, která dále zvyšuje riziko úmrtí.
The mortality of cardiogenic shock remains high despite current progress in revascularisation and the supportive treatment of myocardial infarction. An activation of systemic inflammation may appear in one fifth of the cases of cardiogenic shock and as such may further increase the risk of death.
- MeSH
- cévní rezistence MeSH
- farmakoterapie metody využití MeSH
- infarkt myokardu etiologie komplikace terapie MeSH
- kardiogenní šok mortalita patofyziologie terapie MeSH
- lidé MeSH
- medicína založená na důkazech trendy MeSH
- omega-N-methylarginin MeSH
- oxid dusnatý škodlivé účinky toxicita MeSH
- podpůrné srdeční systémy využití MeSH
- revaskularizace myokardu metody využití MeSH
- sepse etiologie imunologie patofyziologie MeSH
- syndrom systémové zánětlivé reakce patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Nitric oxide production by the hemocytes of the last instar larvae and sessile pharate prepupa of Galleria mellonella (Lepidoptera: Pyralidae) was demonstrated in vitro in response to preparations of bacterial lipopolysaccharide (LPS) from Escherichia coli using the Griess reaction. Augmented, dose dependent nitric oxide production was observed in the pharate prepupal hemocytes compared with larval hemocytes. This was partially reversed in a dose dependent manner with S-methyl thiourea (SMT), a specific inhibitor of inducible nitric oxide synthase (iNOS). A decrease in NO production was also observed when non-selective inhibitors such as N(G)-nitro-L-arginine (L-NAME) and N-omega-nitro-L-arginine (L-NNA) were used, albeit the inhibition was not to the extent of SMT. Challenge with the entomopathogenic Gram-negative bacterium Photorhabdus asymbiotica also enhanced NO production by hemocytes of both stages. SMT, alone or in combination with P. asymbiotica significantly decreased levels of NO production. However, it was observed that phenoloxidase activity (a cascade for innate immune responses) was independent of NO production stimulation. NO donors, S-nitroso-N-acetyl-penicillamine (SNAP) and diethylenetriamine NO adduct (DETA/NO) at various concentrations (100-500 microM) resulted in the lysis of hemocytes dose dependently. The nitrite production in these cases was however similar to LPS stimulation (10 microg/mL) and 1.5-3 fold lower than those observed upon P. asymbiotica (2.5 x 10(7) cfu/mL) stimulation. Survival analysis (Kaplan-Meier) following injection of P. asymbiotica alone or in combination with SMT revealed that only 12.5% (median survival 25.5 h) of co-injected larvae of G. mellonella survived in comparison to 28.6% (median survival 29 h) survivors in P. asymbiotica alone-injected groups till the end of the study. In contrast, co-injected pharate prepupa survived longer (median survival 28 h) than the P. asymbiotica alone-injected individuals (median survival 24 h); however, both co-injected and P. asymbiotica-injected groups showed 100% mortality at the end of the study. Based on the above, we propose that although NO production is involved in cellular immune responses of this insect to bacterial infection it does not appear to be a part of the signalling pathway that initiates the prophenoloxidase (PPO) cascade, and the extended NO production/overproduction by pharate prepupal hemocytes could result in cytotoxic rather than cytoprotective effects compared with larval hemocytes.
- MeSH
- cytoprotekce fyziologie MeSH
- donory oxidu dusnatého farmakologie MeSH
- hemocyty metabolismus účinky léků MeSH
- kukla metabolismus MeSH
- larva metabolismus MeSH
- lipopolysacharidy farmakologie MeSH
- můry cytologie MeSH
- oxid dusnatý antagonisté a inhibitory biosyntéza toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- ischemie mozku MeSH
- kognice fyziologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mozkový krevní oběh MeSH
- oxid dusnatý fyziologie škodlivé účinky toxicita MeSH
- paměť fyziologie MeSH
- synthasa oxidu dusnatého antagonisté a inhibitory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- hodnotící studie jako téma MeSH
- lidé MeSH
- místní státní správa MeSH
- ochrana veřejného zdraví MeSH
- oxid dusičitý * analýza metabolismus škodlivé účinky toxicita MeSH
- oxid dusnatý * analýza fyziologie metabolismus škodlivé účinky toxicita MeSH
- statistika jako téma MeSH
- výfukové emise vozidel * analýza toxicita MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- znečištění ovzduší * prevence a kontrola škodlivé účinky MeSH
- Check Tag
- lidé MeSH
