No abstract

Liver fibrosis represents an overaccumulation of extracellular matrix (ECM). This study was designed to investigate the effect of chrysin on established ECM overproduction in carbon tetrachloride (CCl4) mouse liver fibrosis. Experimental fibrosis was induced by intraperitoneal injection of 2 mL/kg CCl4 twice a week, for 7 weeks. Mice were orally treated with 3 doses of chrysin (5,7-dihydroxyflavone). For the assessment of the spontaneous reversion of fibrosis, CCl4-treated mice were investigated after 2 weeks of recovery time. Silymarin was used as a standard of liver protection. In fibrotic livers, the results showed the upregulation of collagen I (Col I) and tissue inhibitors of metalloproteinase 1 (TIMP-1) and modulation of matrix metalloproteinases (MMPs), which led to an altered ECM enriched in Col, confirmed as well by electron microscopy investigations. Treatment with chrysin significantly reduced ultrastructural changes, downregulated Col I, and restored TIMP-1/MMP balance, whereas in the group observed for the spontaneous regression of fibrosis, they remained in the same pattern with fibrotic livers. In this study, we have shown chrysin efficacy to attenuate dose-dependent CCl4-stimulated liver ECM accumulation by regulation of MMP/TIMP imbalance and inhibition of Col production. We have shown the dose-dependent chrysin efficiency in attenuation of CCl4-induced liver ECM accumulation by regulation of MMP/TIMP imbalance and inhibition of Col production. Our findings suggest that chrysin oral administration may introduce a new strategy for treating liver fibrosis in humans.

The first milk after birth is also known as colostrum. The composition of animal and human colostrum depends very much on different factors such as: animal species, animal breed and genetical characteristics, feeding program, diet. Bovine colostrum is used in different therapies due to its composition in nutraceuticals, but also because the cow gives high quantity colostrum compared to other animal species (goats or ewes). The immunological properties of colostrum are acknowledged in various studies. Due to its immunoglobiline content, it is an alternative therapy in immunity enhancement. Colostrum is also used in athletes' supplementation plan with very good results in their competition performance. Dry matter composition of cow, goat and ewe's colostrum can give very good information about the nutritional composition, especially proteins. Thus, proteins, lipids, minerals, vitamins are significantly higher in colostrum right after parturition and decrease very much in time in mature milk. Lactose -in most of the studies -presents an increase in concentration from colostrum to milk. Our study reflects the highest content of dry matter in ewe colostrum, with significant decrease in goat and cow. Total lipid content was highest also in ewe's colostrum, lower in cow's, and the lowest in goat colostrum. In most samples, minerals (copper, manganese, zinc) had -the highest concentration in colostrum milking with a decrese from the 6 hour colostrum to the 48 hour colostrum collected after parturition. Iron composition increases in ewe colostrum from the 6 hours to 48 hours.

The objective of our study was to determine the effects of clinoptilolite supplemented in colostrum on the blood serum protein electrophoretic pattern of new-born calves. Methods: Romanian Black and White new-born calves involved in the study were divided into 3 groups: the control group (C) that received colostrum without clinoptilolite, and experimental groups I (E1) and II (E2) that received colostrum supplemented with 0.5% and 2% clinoptilolite, respectively. The concentration of total protein and protein fractions (albumin, α1-globulin, α2-globulin, β-globulin and γ-globulin) were analyzed by electrophoresis on cellulose acetate. Results: At hour 30 after birth, concentrations of γ-globulins, β-globulin and total protein in E1 group of calves were higher than in control group by 42.11% (p < 0.05), 28.48% (p > 0.05) and 18.52% (p > 0.05), respectively, and were higher, but not significantly, in group E2 compared to the control group. This was in accordance with a significant lower albumin/globulin ratio in groups E1 and E2 (29.35%, p < 0.05 and 35.87%, p < 0.05, respectively) than in control group at 30 h postpartum, which indicates an obvious increase of the globulins fraction in experimental groups. The conclusion: Clinoptilolite was effective in improving passive transfer in new-born calves, but it was more effective if added in colostrum with a dose of 0.5% than with a dose of 2%.

Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients. In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B. Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles. Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation. Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-α and IL-6 immunoreactivity, together with mRNA upregulation. Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes. Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation. The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction.