Metabolic transformation of cancer cells leads to the accumulation of lactate and significant acidification in the tumor microenvironment. Both lactate and acidosis have a well-documented impact on cancer progression and negative patient prognosis. Here, we report that cancer cells adapted to acidosis are significantly more sensitive to oxidative damage induced by hydrogen peroxide, high-dose ascorbate, and photodynamic therapy. Higher lactate concentrations abrogate the sensitization. Mechanistically, acidosis leads to a drop in antioxidant capacity caused by a compromised supply of nicotinamide adenine dinucleotide phosphate (NADPH) derived from glucose metabolism. However, lactate metabolism in the Krebs cycle restores NADPH supply and antioxidant capacity. CPI-613 (devimistat), an anticancer drug candidate, selectively eradicates the cells adapted to acidosis through inhibition of the Krebs cycle and induction of oxidative stress while completely abrogating the protective effect of lactate. Simultaneous cell treatment with tetracycline, an inhibitor of the mitochondrial proteosynthesis, further enhances the cytotoxic effect of CPI-613 under acidosis and in tumor spheroids. While there have been numerous attempts to treat cancer by neutralizing the pH of the tumor microenvironment, we alternatively suggest considering tumor acidosis as the Achilles' heel of cancer as it enables selective therapeutic induction of lethal oxidative stress.
- MeSH
- acidóza patofyziologie MeSH
- citrátový cyklus účinky léků MeSH
- energetický metabolismus MeSH
- fyziologická adaptace MeSH
- glukosa metabolismus MeSH
- glykolýza MeSH
- kapryláty farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- kyselina mléčná metabolismus MeSH
- lidé MeSH
- mitochondrie účinky léků metabolismus patologie MeSH
- nádorové buňky kultivované MeSH
- nádorové mikroprostředí * MeSH
- nádory farmakoterapie metabolismus patologie MeSH
- oxidační stres MeSH
- protinádorové látky farmakologie MeSH
- sulfidy farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
We have evaluated the therapeutic effect of a compound mixture of caprylic acid (200 mg/kg fish), organic iron (0.2% of diet) and mannan oligosaccharide (0.4% of diet) in gilthead sea bream, Sparus aurata Linnaeus, infected with Sparicotyle chrysophrii Beneden et Hesse, 1863 in controlled conditions. One hundred and ten reared and S. chrysophrii-free fish (197 g) located in a cement tank were infected by the parasite two weeks following the addition of 150 S. chrysophrii-infected fish (70 g). Growth parameters and gill parasitic load were measured in treated against control fish after a ten-week-period. Differences in final weight, feed conversion ratio, specific growth rate and feed efficiency were not statistically significant between the experimental groups, suggesting no evident effect with respect to fish growth during the study period. Although the prevalence of S. chrysophrii was not affected by the mixture at the end of the experiment, the number of adults and larvae was significantly lower. The mean intensity encompassing the number of adults and larvae was 8.1 in treated vs 17.7 in control fish. Individual comparisons of gill arches showed that the preferred parasitism site for S. chrysophrii it the outermost or fourth gill arch, consistently apparent in fish fed the modified diet and in control fish. In conclusion, the combined application of caprylic acid, organic iron and mannan oligosaccharide can significantly affect the evolution of infection with S. chrysophrii in gilthead sea bream, being capable of reducing adult and larval stages of the monogenean. However, no difference in growth improvement was observed after the trial period, potentially leaving space for further optimisation of the added dietary compounds.
- MeSH
- fixní kombinace léků MeSH
- infekce červy třídy Trematoda farmakoterapie veterinární MeSH
- kapryláty farmakologie MeSH
- mannany farmakologie MeSH
- mořan zlatý parazitologie MeSH
- nemoci ryb farmakoterapie MeSH
- oligosacharidy farmakologie MeSH
- potravní doplňky MeSH
- Trematoda účinky léků MeSH
- železo farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The effect of caprylic acid (CA) on Campylobacter jejuni in chickens was evaluated using two approaches: dietary supplementation or surface treatment of chilled chicken carcasses. To analyze the dietary effect of CA, individually housed broiler chickens (n = 48) were artificially infected with C. jejuni VFU612 (10(6) colony-forming units [CFU]/bird) on the 21st and 35th days of life. Dietary CA (2.5 and 5 g/kg of feed, fed throughout the entire experiment) significantly decreased C. jejuni shedding (p<0.05). However, the effect only lasted for 3-7 days after infection. The numbers of Campylobacter shed by the positive control birds reached its maximum on the 37th day of life, while on that same day, both Treatment I and Treatment II groups shed significantly lower (p<0.05) numbers of Campylobacter (by 0.8 and 1.8 log10 CFU/g, respectively). Also, peak shedding was delayed by 1 day in both treated groups. After euthanasia of each chicken on the 42nd day of life, no differences in Campylobacter counts in the crop, gizzard, ileum, and cecum were found between the positive control and the treated groups (p>0.05). Surface contamination of the chilled chicken halves was performed with C. jejuni VFU612 (clinical isolate) and CCM6214 (collection strain). Surface treatment with CA at 1.25 and 2.5 mg/mL for 1 min significantly reduced C. jejuni VFU612 contamination of chicken skin (p<0.05) by 0.29-0.53 and 1.14-1.58 log10 CFU/g of skin, respectively. Counts of C. jejuni CCM6214 were reduced by 0.68-1.65 log10 CFU/g of skin). In conclusion, dietary CA affected numbers of C. jejuni in the gastrointestinal contents of chickens, whereas surface treatment reduced C. jejuni contamination in processed chicken carcasses.
- MeSH
- antiinfekční látky farmakologie MeSH
- Campylobacter jejuni účinky léků MeSH
- drůbež mikrobiologie MeSH
- kapryláty farmakologie MeSH
- kontaminace potravin MeSH
- krmivo pro zvířata * MeSH
- kur domácí mikrobiologie MeSH
- manipulace s potravinami MeSH
- počet mikrobiálních kolonií MeSH
- potravinářská mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Oregano essential oil (OEO) and caprylic acid (CA) are highly aromatic natural antimicrobials with limited individual application in food. We proved their combined additive effect when used in meat. Application of 0.5% CA and 0.2% OEO (v/w) with 0.1% of citric acid in vacuum packed minced beef inoculated with Listeria monocytogenes at a concentration of 5 log cells/g reduced counts of lactic acid bacteria by 1.5 log CFU/g and counts of psychrotrophic bacteria and L. monocytogenes by more than 2.5 log CFU/g at the end of storage at 3°C for 10 days. In sensory evaluation the samples with OEO showed during the whole experiment statistically better scores than control, whereas the samples treated with CA showed worse colour attributes.
- MeSH
- antiinfekční látky farmakologie MeSH
- barva MeSH
- chemické jevy MeSH
- dobromysl (rod) chemie MeSH
- kapryláty farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- kontaminace potravin prevence a kontrola MeSH
- konzervace potravin MeSH
- Lactobacillaceae účinky léků růst a vývoj MeSH
- lidé MeSH
- Listeria monocytogenes účinky léků růst a vývoj MeSH
- maso analýza mikrobiologie MeSH
- obaly potravin MeSH
- odoranty analýza MeSH
- oleje prchavé farmakologie MeSH
- počet mikrobiálních kolonií MeSH
- potravinářská mikrobiologie MeSH
- skot MeSH
- spotřebitelská bezpečnost produktů MeSH
- vakuum MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The effect of caprylic acid, either in its pure form, or as Akomed R, on the microbial community of the stomach and caecum of farmed rabbits was investigated. This fatty acid, which is often added to the diet of farmed rabbits to reduce mortality rates was shown to reduce the number of coliforms isolated from both the stomach and the caecum. Moreover, it led to a reduction in the total number of anaerobic bacteria isolated from the caecum, but not for those isolated from the stomach. Its mode of action remains unclear, but here it is shown by use of both DGGE and TRFLP analysis that these changes are not confined to one specific group of bacteria, but rather affects a number of species.
- MeSH
- cékum mikrobiologie MeSH
- dieta veterinární MeSH
- kapryláty farmakologie MeSH
- králíci MeSH
- krmivo pro zvířata analýza MeSH
- potravní doplňky MeSH
- žaludek mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- MeSH
- chlorid vápenatý farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- glukosa antagonisté a inhibitory metabolismus MeSH
- inhibiční koncentrace 50 MeSH
- kapryláty farmakologie MeSH
- mastné kyseliny farmakologie MeSH
- Salmonella metabolismus MeSH
- techniky in vitro MeSH
- viabilita buněk účinky léků MeSH
