CONTEXT: Monoestolides belonging to the fatty acid-hydroxy fatty acid (FAHFA) family have recently emerged as promising insulin sensitizers. OBJECTIVE: To investigate and compare impact of two selected FAHFA isomers, namely 9-hexadecanoyloxy-octadecanoic acid [9-PAHSA] and 9-(9Z-octadecenoyloxy)-octadecanoic acid [9-OAHSA], on intact livers in C57BL/6J mice. MATERIALS AND METHODS: Short-term in vivo study with intragastric gavage of 13 mg/kg of substances. Morphological, biochemical and high-resolution respirometric assessment of plasma and liver tissue or homogenates thereof. RESULTS: The 9-OAHSA-gavaged mice had the highest final total body weight, the lowest free fatty acid circulating levels and the highest plasma activities of both ALT and AST. No significant changes of ambient glycaemia were found, however 9-PAHSA-gavaged mice tended to have lower glycaemia than other animals. Respirometry proved no substance-dependent differences. DISCUSSION AND CONCLUSION: 9-PAHSA was more metabolically beneficial and less hepatotoxic than 9-OAHSA. Bioenergetic machinery of liver homogenates seemed unaffected at our FAHFA dose.
OBJECTIVES: (i) to determine the extent of oxidative stress and DNA damage and repair using a panel of selected markers in patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM), (ii) to find their possible relationships with diabetes compensation and duration, and finally (iii) to test for the effect of functional polymorphisms in the 8-oxoguanin DNA glycosylase (rs1052133), catalase (rs1001179) and superoxide dismutase (rs4880) genes on respective intermediate phenotypes. METHODS: A total of 207 subjects (23 children and 44 adults with T1DM, 52 adult patients with T2DM and 88 healthy adult control subjects) were enrolled in the study. The following markers of redox state were determined in participants: erythrocyte superoxide dismutase (Ery-SOD), whole blood glutathione peroxidase (WB-GPx), erythrocyte glutathione (Ery-GSH), plasma total antioxidant capacity (P-tAOC) and plasma malondialdehyde (P-MDA). Furthermore, the extent of DNA damage and repair was ascertained using the following parameters: DNA single strand breaks (DNAssb), DNA repair capacity (DNArc) and DNA repair index (DNRI). RESULTS: Comparison of T1DM vs. T2DM patients revealed significantly higher Ery-GSH content (P < 0.0001) and significantly lower Ery-SOD activity (P = 0.0006) and P-tAOC level (P < 0.0001) in T1DM subjects. T2DM diabetics exhibited a significant increase in DNAssb (P < 0.0001) and significant decrease in both DNArc (P < 0.0001) and DNRI (P < .0001) compared with T1DM patients. Patient's age (irrespective of DM type) significantly correlated with DNAssb (r = 0.48, P < 0.0001), DNArc (r = -0.67, P < 0.0001) and DNRI (r = -0.7, P < 0.0001). Allele frequencies of all studied polymorphisms did not exhibit any significant association with the investigated parameters. CONCLUSION: We demonstrated significant age- and DM type-related changes of oxidative DNA modification and capacity for its repair in subjects with T1DM and T2DM.
- MeSH
- alely MeSH
- diabetes mellitus 1. typu krev genetika MeSH
- diabetes mellitus 2. typu krev genetika MeSH
- dítě MeSH
- DNA-glykosylasy krev genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- glutathion krev MeSH
- glutathionperoxidasa krev MeSH
- katalasa krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- malondialdehyd krev MeSH
- oprava DNA MeSH
- oxidační stres MeSH
- polymorfismus genetický MeSH
- poškození DNA MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- superoxiddismutasa krev genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Diabetes mellitus, especially when complicated with decline of renal function due to diabetic nephropathy (DN), is associated with accumulation of advanced glycation end products (AGEs) exerting their adverse effects via receptor of AGE (RAGE). Soluble RAGE (sRAGE) is a truncated form of RAGE functioning as an inhibitor of AGE-mediated signalling. We studied relationships between sRAGE, renal function and genetic variability in the AGER gene in diabetic subjects. Study comprised a total of 265 diabetics (type 1 or 2 or LADA) with normoalbuminuria (n = 94) or DN (n = 171). sRAGE (assessed by ELISA) was significantly higher in DN than normoalbuminuria subjects (P = 0.007) and positively correlated with age, S-urea, S-creatinine and albuminuria and AGEs (determined spectrofluorimetrically), negatively with GFR (all P < 0.05); however, multivariate regression revealed that GFR was the only independent variable associated with sRAGE (P = 0.047). sRAGE did not correspond with carrier state of risk-haplotype copies (RAGE2) (P > 0.05). In conclusion, GFR is a principal determinant of sRAGE concentration and gradual sRAGE increase in subjects with advancing impairment of renal function is paralleled by AGEs.
- MeSH
- diabetické nefropatie genetika patofyziologie MeSH
- ELISA MeSH
- financování organizované MeSH
- genetická variace MeSH
- haplotypy MeSH
- hodnoty glomerulární filtrace MeSH
- lidé středního věku MeSH
- lidé MeSH
- produkty pokročilé glykace krev MeSH
- průřezové studie MeSH
- receptory imunologické genetika MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- MeSH
- cyklohexany farmakologie MeSH
- dietní tuky aplikace a dávkování farmakologie MeSH
- fenylalanin analogy a deriváty MeSH
- glukosa metabolismus MeSH
- hypoglykemika farmakologie MeSH
- krysa rodu rattus MeSH
- tělesná hmotnost účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
