Long-Term Cola Intake Does Not Cause Evident Pathological Alterations in the Femoral Bone Microstructure: An Animal Study in Adult Mice.

Short-term animal experiments and association studies in humans have shown that cola intake may have a detrimental impact on bone mineral density (BMD); however, other bone parameters have not been investigated. This study examined the effects of long-term cola consumption on the femoral bone microstructure using adult mice (n = 32) as an animal model, which were divided into water and cola groups depending on whether they received water or cola along with a standard rodent diet for 6 months. Micro-computed tomography revealed that cola intake did not significantly affect all measured parameters characterizing trabecular bone mass and microarchitecture, as well as cortical microarchitecture and geometry in both sexes, although a slight deterioration of these parameters was noted. Cola consumption also resulted in a slightly, statistically insignificant worsening of bone mechanical properties. In contrast to female mice, males receiving cola had a lower area of primary osteons' vascular canals. Nevertheless, long-term cola intake did not cause evident pathological alterations in the femur of adult mice, possibly due to a balanced diet and no restriction of physical activity. Therefore, the adverse effects of cola consumption on BMD, the only bone parameter studied so far, may be caused by other risk and lifestyle factors.

Variability of endogenous deoxyribonuclease activity and its pathophysiological consequences.

Deoxyribonucleases (DNases) are enzymes that cleave DNA. Some DNases are secreted outside of cells where they can cleave extracellular DNA (ecDNA). High concentration of ecDNA is associated with diseases such as sepsis, preeclampsia, and systemic lupus. DNA can be released from dying cells and is immunogenic. DNases cleave ecDNA and might prevent activation of the immune system. Low DNase activity could be disadvantageous in diseases where high amounts of ecDNA are released from dying cells. The relationship between DNase activity and ecDNA remains unknown. The lack of standard values in DNase activity makes the studies difficult to compare. This review focuses on summarizing methods for DNase activity measurements, the possible implication of decreased DNase activity in diseases, and the impact on diseases associated with a high concentration of ecDNA.

Plasma DNA and deoxyribonuclease are associated with glucose metabolism in healthy mice.

It is currently unknown why obesity leads in some patients to prediabetes and metabolic syndrome. Microinflammation potentially caused by extracellular DNA is supposed to be involved. The aim of this cross-sectional study in healthy mice was to analyze the association between plasma extracellular DNA and glucose metabolism. Fasting glycemia and insulin were measured in healthy adult female mice that subsequently underwent an oral glucose tolerance test. Indices of glucose metabolism and insulin sensitivity were calculated. DNA was isolated from plasma and quantified fluorometrically. Deoxyribonuclease (DNase) activity of plasma was measured using the single radial enzyme diffusion method. Fasting glycemia correlated negatively with both, extracellular DNA and DNase (r = -0.44 and r = -0.32, respectively). DNase was associated positively with the incremental area under curve (r = 0.35), while extracellular DNA correlated negatively with total area under curve of glycemia during oral glucose tolerance test (r = -0.34). Measures of insulin sensitivity were found to be associated with neither extracellular DNA, nor DNase. The hypothesis of an association of low DNase with increased fasting glucose was partially proved. Surprisingly, low extracellular DNA is associated with higher fasting glucose and lower glucose tolerance in mice. As novel therapeutic targets for prediabetes and metabolic syndrome are highly needed, this study provides novel unexpected associations within the limitations of the focus on physiological variability as it was conducted on healthy mice. The causality of these associations should be proved in further interventional experiments.

Long-Term Consumption of a Sugar-Sweetened Soft Drink in Combination with a Western-Type Diet Is Associated with Morphological and Molecular Changes of Taste Markers Independent of Body Weight Development in Mice.

We investigated whether the long-term intake of a typical sugar-sweetened soft drink (sugar-sweetened beverage, SSB) alters markers for taste function when combined with a standard diet (chow) or a model chow mimicking a Western diet (WD). Adult male CD1 mice had ad libitum access to tap water or SSB in combination with either the chow or the WD for 24 weeks. Energy intake from fluid and food was monitored three times a week. Cardiometabolic markers (body weight and composition, waist circumference, glucose and lipid profile, and blood pressure) were analyzed at the end of the intervention, as was the number and size of the fungiform papillae as well as mRNA levels of genes associated with the different cell types of taste buds and taste receptors in the circumvallate papillae using a cDNA microarray and qPCR. Although the overall energy intake was higher in the WD groups, there was no difference in body weight or other cardiometabolic markers between the SSB and water groups. The chemosensory surface from the fungiform papillae was reduced by 36 ± 19% (p < 0.05) in the WD group after SSB compared to water intake. In conclusion, the consumption of the SSB reduced the chemosensory surface of the fungiform papillae of CD1 mice when applied in combination with a WD independent of body weight. The data suggest synergistic effects of a high sugar-high fat diet on taste dysfunction, which could further influence food intake and promote a vicious cycle of overeating and taste dysfunction.

Beneficial effect of sugar-sweetened beverages on the risk of urinary tract infections.

Urinary tract infections (UTI) are among the most common bacterial infections. Drinking more liquids increases the frequency of urination and it is recommended as part of the prevention and/or management of UTI. The intake of sugar-sweetened beverages (SSB) is associated with obesity, diabetes and metabolic syndrome. However, cola and other SSB increase liquid intake and diuresis and could, thus, affect the risk of UTI and its complications. We hypothesize that intake of cola has a protective effect on UTI and pyelonephritis. Using an animal model of UTI, we have confirmed that dehydration with minimal urine output leads to higher bacterial counts in the kidneys in comparison to control mice (p = 0.01). The intake of SSB increased liquid intake and thus also diuresis and decreased renal bacterial counts as a marker of induced pyelonephritis (p = 0.036). The preliminary results show that dehydration is a risk factor for UTI and that higher diuresis induced by drinking SSB might be protective against pyelonephritis. The underlying mechanisms could include increased voiding frequency but potentially also active compounds in cola such as caffeine. These findings might have implications for the management of individuals at high risk of UTI. Further studies should verify the hypothesis and evaluate the practical relevance of this concept.

Early Dynamics of Plasma Dna in a Mouse Model of Sepsis.

Concentration of extracellular DNA (ecDNA) in plasma of septic patients is higher in comparison to healthy controls and is associated with worse prognosis in intensive care patients. Decrease of ecDNA in plasma by treatment with deoxyribonuclease (DNase) showed to have beneficial effects in animal models of sepsis. A previously published study showed that timing of DNase application is crucial for the effect of DNase. No published study monitored plasma ecDNA dynamics during sepsis in detail yet. The aim of our study was to describe the early dynamics of plasma ecDNA but also plasma DNase activity in a mouse model of sepsis. Sepsis was induced using intraperitoneal injection of E. coli and mice were euthanized every hour to obtain sufficient volume of plasma. Our results show that the concentration of plasma ecDNA is rising continuously during the first 5 h after infection and is 20-fold higher 5 h after induction of sepsis in comparison to control mice. Subcellular origin of plasma ecDNA was analyzed but fundamental differences in dynamics between nuclear and mitochondrial ecDNA were not found. DNase activity in plasma seems to rise slowly until the fourth hour, but the interindividual variability is high. In conclusion, this is the first study that describes the dynamics of plasma ecDNA and DNase activity in early sepsis in detail. Our study is the basis for further studies focused on the timing of exogenous DNase treatment in sepsis. Additional studies will be needed to monitor plasma ecDNA in later time points that are more clinically relevant.

Fetal DNA does not induce preeclampsia-like symptoms when delivered in late pregnancy in the mouse.

INTRODUCTION: The etiology of preeclampsia is unclear. Fetal DNA is present in higher concentrations in the plasma of pregnant women suffering from preeclampsia than in the plasma of healthy pregnant women. A previously published study has shown that human fetal DNA injected into pregnant mice induces preeclampsia-like symptoms when administered between gestation days 10-14. The aim of our experiment was to determine whether or not similar effects would be induced by administration of human and mouse fetal DNA, as well as mouse adult DNA and lipopolysaccharide during late pregnancy in the mouse. METHODS: Experimental animals were injected daily intraperitoneally during gestation days 14-18 with either saline - negative control, lipopolysaccharide - positive control, or various types of DNA. On gestation day 19, blood pressure and proteinuria were measured, and placental and fetal weights were recorded. RESULTS: Fetal and placental hypotrophy were induced only by lipopolysaccharide (p < 0.001). Neither fetal nor adult DNA induced changes in fetal/placental weight. None of the experimental groups had higher blood pressure or urinary protein in comparison to saline treated animals. DISCUSSION: In our experiment, we found that there was no effect from intraperitoneally injected human fetal DNA, mouse fetal DNA, or mouse adult DNA on pregnant mice. Additionally, relatively high doses of various types of DNA did not induce preeclampsia-like symptoms in mice when administered in late pregnancy. Our negative results support the hypothesis that the increase of fetal DNA circulating in maternal circulation during the third trimester is rather a consequence than a cause of preeclampsia.

Deoxyribonuclease partially ameliorates thioacetamide-induced hepatorenal injury.

Several recent studies have shown that liver injury is associated with the release of DNA from hepatocytes. This DNA stimulates innate immunity and induces sterile inflammation, exacerbating liver damage. Similar mechanisms have been described for acute renal injury. Deoxyribonuclease degrades cell-free DNA and can potentially prevent some of the induced tissue damage. This study analyzed the effects of thioacetamide-induced hepatorenal injury on plasma DNA in rats. Plasma DNA of both nuclear and mitochondrial origin was higher in thioacetamide-treated animals. Administration of deoxyribonuclease resulted in a mild, nonsignificant decrease in total plasma DNA and plasma DNA of mitochondrial origin but not of nuclear origin. This was accompanied by a decrease in bilirubin, creatinine, and blood urea nitrogen as markers of renal function. In conclusion, the study confirmed the hepatotoxic and nephrotoxic effect of thioacetamide. The associated increase in cell-free DNA seems to be involved in hepatorenal pathogenesis because treatment with deoxyribonuclease resulted in a partial prevention of hepatorenal injury. Further experiments will focus on the effects of long-term treatment with deoxyribonuclease in other clinically more relevant models. Clinical studies should test endogenous deoxyribonuclease activity as a potential risk determinant for kidney or liver failure.NEW & NOTEWORTHY Thioacetamide-induced hepatorenal injury resulted in higher plasma cell-free DNA. Deoxyribonuclease decreased average cell-free DNA of mitochondrial origin but not nuclear origin. Deoxyribonuclease partially prevented hepatorenal injury in rats.