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Long-term metabolic consequences of acute dioxin exposure differ between male and female mice.

ABSTRACT: Epidemiological studies have consistently shown an association between exposure to environmental pollutants and diabetes risk in humans. We have previously shown that direct exposure of mouse and human islets (endocrine pancreas) to the highly persistent pollutant TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) causes reduced insulin secretion ex vivo. Furthermore, a single high-dose of TCDD (200 µg/kg) suppressed both fasting and glucose-induced plasma insulin levels and promoted beta-cell apoptosis after 7 days in male mice. The current study investigated the longer-term effects of a single high-dose TCDD injection (20 µg/kg) on glucose metabolism and beta cell function in male and female C57Bl/6 mice. TCDD-exposed males displayed modest fasting hypoglycemia for ~4 weeks post-injection, reduced fasting insulin levels for up to 6 weeks, increased insulin sensitivity, decreased beta cell area, and increased delta cell area. TCDD-exposed females also had long-term suppressed basal plasma insulin levels, and abnormal insulin secretion for up to 6 weeks. Unlike males, TCDD did not impact insulin sensitivity or islet composition in females, but did cause transient glucose intolerance 4 weeks post-exposure. Our results show that a single exposure to dioxin can suppress basal insulin levels long-term in both sexes, but effects on glucose homeostasis are sex-dependent.

SUBMITTER: Hoyeck MP

PROVIDER: S-EPMC6989671 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Long-term metabolic consequences of acute dioxin exposure differ between male and female mice.

Hoyeck Myriam P MP Blair Hannah H Ibrahim Muna M Solanki Shivani S Elsawy Mariam M Prakash Arina A Rick Kayleigh R C KRC Matteo Geronimo G O'Dwyer Shannon S Bruin Jennifer E JE

Scientific reports 20200129 1

Epidemiological studies have consistently shown an association between exposure to environmental pollutants and diabetes risk in humans. We have previously shown that direct exposure of mouse and human islets (endocrine pancreas) to the highly persistent pollutant TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) causes reduced insulin secretion ex vivo. Furthermore, a single high-dose of TCDD (200 µg/kg) suppressed both fasting and glucose-induced plasma insulin levels and promoted beta-cell apoptosis ...[more]

PMID: 31996693

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Project description:PurposeResistance to antibiotics is a major problem of public health. One of the alternative therapies is silver - more and more popular because of nanotechnology development and new possibilities of usage. As a component of colloid, powder, cream, bandages, etc., nanosilver is often recommended to treat the multidrug-resistant pathogens and we can observe its overuse also outside of the clinic where different physicochemical forms of silver nanoformulations (e.g. size, shape, compounds, surface area) are introduced. In this research, we described the consequences of long-term bacteria exposure to silver nanoformulations with different physicochemical properties, including changes in genome and changes of bacterial sensitivity to silver nanoformulations and/or antibiotics. Moreover, the prevalence of exogenous resistance to silver among multidrug-resistant bacteria was determined.Materials and methodsGram-negative and Gram-positive bacteria strains are described as sensitive and multidrug-resistant strains. The sensitivity of the tested bacterial strains to antibiotics was carried out with disc diffusion methods. The sensitivity of bacteria to silver nanoformulations and development of bacterial resistance to silver nanoformulations has been verified via determination of the minimal inhibitory concentrations. The presence of sil genes was verified via PCR reaction and DNA electrophoresis. The genomic and phenotypic changes have been verified via genome sequencing and bioinformatics analysis.ResultsBacteria after long-term exposure to silver nanoformulations may change their sensitivity to silver forms and/or antibiotics, depending on the physicochemical properties of silver nanoformulations, resulting from phenotypic or genetic changes in the bacterial cell. Finally, adaptants and mutants may become more sensitive or resistant to some antibiotics than wild types.ConclusionApplication of silver nanoformulations in the case of multiple resistance or multidrug-resistant bacterial infection can enhance or decrease their resistance to antibiotics. The usage of nanosilver in a clinic and outside of the clinic should be determined and should be under strong control. Moreover, each silver nanomaterial should be considered as a separate agent with a potential different mode of antibacterial action.

Project description:BackgroundSeveral of the most extensively used risk prediction tools for coronary artery bypass grafting outcomes include female sex as an independent risk factor for postoperative outcomes. It is not clear whether this putative increased surgical risk impacts long-term survival. This study aimed to assess sex differences in 10-year all-cause mortality.MethodsRetrospective analysis of 5340 consecutive patients undergoing primary isolated coronary artery bypass surgery, performed from 2000 to 2015, in a Portuguese level III Hospital. The primary endpoint was all-cause mortality at ten years. We employed an overlap weighting algorithm to minimize confounding. Its target population highlights patients with the most overlap in their observed characteristics, and its corresponding estimand is the average treatment effect in the overlap population.ResultsWe identified that 5340 patients underwent isolated CABG: 1104 (20.7%) were female, and 4236 (79.3%) were male. Sixteen patients were lost to follow-up (0.3%). The median follow-up time was 12.79 (IQR, 9.52-16.66) years: 12.68 (IQR, 9.48-16.54) years for the male patient group and 13.13 (IQR, 9.75-16.98) years for the female patient group. The primary endpoint of all-cause mortality at ten years occurred in 1106 patients (26.1%) in the male patient group, compared with 315 (28.5%) in the female patient group. The unweighted survival analysis for both groups reveals the worst long-term prognosis for the female cohort (hazard ratio, 1.22; 95% CI, 1.10 to 1.35; p < 0.001), while in the overlap weighted survival analysis, such long-term difference in prognosis disappears (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; p = 0.693).ConclusionIn this longitudinal, population-level analysis of patients undergoing primary, isolated CABG, we demonstrated that the female sex is not associated with increased long-term all-cause mortality compared to their male counterparts. Thus, sex should not influence the undertaking of an adequate revascularization strategy.

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Long-term metabolic consequences of acute dioxin exposure differ between male and female mice.

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Long-term metabolic consequences of acute dioxin exposure differ between male and female mice.

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