Vitamin D and COVID-19 in an immunocompromised patient with multiple comorbidities-A Case Report.

Routine 25-OH-Vitamin D3 measurement in COVID-19 patients could be of great importance, either for clinical course estimation or deciding on supplementation.

Influence of cadmium on metallothionein expression and products of lipid peroxidation in the organs of hares (Lepus europaeus Pallas).

Cadmium occurs naturally in the environment and as an anthropogenic pollutant. Exposure to low concentrations of cadmium is inevitable and may produce toxic effects. Another important aspect of cadmium toxicity is its interaction, often antagonistic, with essential elements such as selenium. The aim of this study was to highlight the risks of long-term exposure to low cadmium concentrations, using a scientific and chemical approach and hares (Lepus europaeus Pallas) as model organisms in a field study. Two study areas were monitored. Levels of cadmium and selenium were quantified in the organs of hares, the expression of metallothioneins I + II and the products of lipid peroxidation were determined. The median cadmium concentrations (wet weight) in the muscle, liver, kidney and brain of hares from an exposed group ranged from 0.033 to 0.037, 0.763 to 1.054, 3.090 to 16.594 and 0.016 to 0.087 µg g(-1), respectively; whereas, the median selenium concentrations (wet weight) ranged from 0.100 to 0.108, 0.153 to 0.332, 0.677 to 0.701 and 0.078 to 0.116 µg g(-1), respectively. Expression of the metallothioneins I + II proteins was observed in tissues. Lipid peroxidation (LPO) levels, measured as malondialdehyde (MDA) equivalents, increased with the cadmium concentration. Further research on long-term exposure to low concentrations of cadmium in the environment is needed.

Resolution of liver fibrosis by isoquinoline alkaloid berberine in CCl4-intoxicated mice is mediated by suppression of oxidative stress and upregulation of MMP-2 expression.

Liver fibrosis is the result of chronic liver injury, and it represents a widespread medical problem. The aim of this study is to investigate the antifibrotic activity of isoquinoline alkaloid berberine in carbon tetrachloride (CCl4)-induced damage in mice. Hepatic fibrosis was induced by intraperitoneal (i.p.) administration of CCl4 (2 mL/kg, 20% v/v in olive oil) twice a week for 8 weeks. Berberine at the doses of 3 and 9 mg/kg and silymarin at the dose of 50 mg/kg were given i.p. once daily for the next 2 weeks. CCl4 intoxication increased the levels of serum transaminases and induced oxidative stress in the liver. Hepatic fibrosis was evidenced by a massive deposition of collagen, which coincided with increased expression of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-ß1 and the activation of hepatic stellate cells. The high-dose berberine (9 mg/kg) ameliorated oxidative stress, decreased TNF-α and TGF-ß1 expression, increased the levels of matrix metalloproteinase (MMP)-2, and stimulated the elimination of fibrous deposits. Berberine at the dose of 9 mg/kg exhibited stronger therapeutic activity against hepatic fibrosis than silymarin at the dose of 50 mg/kg. In vitro analyses show an important scavenging activity of berberine against oxygen and nitrogen reactive species. The results of this study suggest that berberine could ameliorate liver fibrosis through the suppression of hepatic oxidative stress and fibrogenic potential, concomitantly stimulating the degradation of collagen deposits by MMP-2.

Metallothioneins I/II expression in rat strains with genetically different susceptibility to experimental autoimmune encephalomyelitis.

OBJECTIVES: Compared to the Dark Agouti (DA), the Albino Oxford (AO) rat strain exhibits lower susceptibility to the induction of experimental autoimmune encephalomyelitis (EAE). Here, we investigated the potential contribution of the heavy metal-binding proteins metallothioneins (MTs) I/II to these effects. METHODS: Rats were immunized with bovine brain homogenate emulsified in complete Freund's adjuvant or only with complete Freund's adjuvant. The expression patterns of MTs mRNA and proteins and tissue concentrations of Zn2+ and Cu2+ were estimated in the brain and in the liver on days 7 and 12 after immunization, by real-time PCR, immunohistochemistry and inductively coupled plasma spectrometry, respectively. Additionally, the hepatic transforming growth factor beta and nuclear factor kappa B immunoreactivities were tested. RESULTS: Clinical signs of EAE were not induced in AO rats, but they upregulated the expression of MT I/II proteins in the brain (hippocampus and cerebellum) and in the liver, similarly as DA rats. The transcriptional activation of MT-I occurred, however, only in DA rats, which accumulated also more zinc in the brain and in the liver. In contrast, intact AO rats had greater hepatic MT-I mRNA immunoreactivity and more Cu2+ in the hippocampus. Besides, in immunized AO rats a high upregulation of transforming growth factor beta and nuclear factor kappa B immunoreactivities was found in several hepatic structures (vascular endothelium, Kupffer cells and hepatocytes). CONCLUSIONS: Our data show that AO and DA rats differ in constitutive and inductive MT-I gene expression in the brain and in the liver, as well as in the hepatic cytokine profile, suggesting that these mechanisms may contribute to the discrepancy in the susceptibility to EAE.

Effects of standardized bilberry fruit extract (Mirtoselect®) on resolution of CCl4-induced liver fibrosis in mice.

Bilberry (Vaccinium myrtillus L) has been traditionally used in the treatment of various liver disorders. The aim of this study was to investigate the effects of bilberry fruit extract (BE) on carbon tetrachloride (CCl(4))-induced hepatic fibrosis. Male Balb/C mice were treated with CCl(4) dissolved in olive oil (20% v/v, 2 ml/kg) intraperitoneally (i.p.), twice a week for 7 weeks. BE (1, 5, and 10 mg/kg) was given to mice for next 15 days, 72 h after the last dose of CCl(4). The CCl(4) administration increased oxidative stress as well as the expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1) in the liver. Furthermore, increased α-smooth muscle actin (α-SMA) expression and hydroxyproline levels indicated activation of hepatic stellate cells (HSCs) and enhanced collagen production. BE 10mg/kg markedly attenuated oxidative stress, decreased TNF-α, TGF-ß1, and α-SMA expression, and eliminated hepatic collagen deposits. These results indicate that BE, in a dose dependent manner, induces the resolution of liver fibrosis by decreasing oxidative stress and inactivating HSCs via down-regulation of fibrogenic cytokines, TGF-ß1 and TNF-α.

Kinetics of tissue iron in experimental autoimmune encephalomyelitis in rats.

To elucidate the role of iron in the pathomechanisms of autoimmune CNS disorders, we estimated the tissue concentrations of Fe(2+) in the brain, spinal cord, and liver in the chronic relapsing form of experimental autoimmune encephalomyelitis (EAE). The disease was induced in Dark Agouti (DA) strain of rats, by subcutaneous injection of bovine brain homogenate in complete Freund's adjuvant (CFA). Control rats consisted of unsensitized rats and of rats treated with CFA or saline. The data obtained by clinical assessment and by inductively coupled plasma spectrometry have shown that the attacks of disease (on the 12th and 22nd post-immunization day) were followed by high accumulation of iron in the liver. Additionally, during the second attack of disease, the decreased concentration of Fe(2+) was found in cervical spinal cord. The data point to regulatory effects of iron and hepatic trace elements regulating mechanisms in the pathogenesis of EAE.

Antifibrotic activity of Taraxacum officinale root in carbon tetrachloride-induced liver damage in mice.

AIM OF THE STUDY: Dandelion (Taraxacum officinale) has been traditionally used in the treatment of various liver disorders. The present study was aimed to assess the efficacy of dandelion root water-ethanol extract (DWE) in carbon tetrachloride (CCl(4))-induced hepatic fibrosis. MATERIALS AND METHODS: The mice were treated with CCl(4) dissolved in olive oil (20%, v/v, 2 ml/kg) intraperitoneally (i.p.), twice a week for 4 weeks. DWE was administered i.p. once daily for next 10 days, in doses of 200 and 600 mg/kg of body weight. The degree of hepatic fibrosis was determined by hydroxyproline content and Mallory trichrome staining. Oxidative stress was determined by measuring hepatic superoxide dismutase (Cu/Zn SOD) activity. The expression and specific tissue distribution of glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (alpha-SMA), and metallothionein (MT) I/II in the liver were determined by immunohistochemistry. RESULTS: Hepatic Cu/Zn SOD activity has been decreased in intoxicated mice and normalized in DWE treated groups. MT I/II immunopositivity was strongly reduced in the CCl(4) group. DWE treatment successfully decreased hepatic fibrinous deposits, restored histological architecture, and modulate the expression of GFAP and alpha-SMA. Concomitantly, MT I/II expression increased in the DWE treated groups. CONCLUSIONS: Our results suggest the therapeutic effect of DWE on CCl(4)-induced liver fibrosis by the inactivation of hepatic stellate cells and the enhancement of hepatic regenerative capabilities. The present results provide scientific evidence to substantiate the traditional use of Taraxacum officinale root in hepatic disorders.

Antifibrotic activity of anthocyanidin delphinidin in carbon tetrachloride-induced hepatotoxicity in mice.

The aim of this study was to investigate the hepatoprotective effects of anthocyanidin delphinidin in carbon tetrachloride (CCl(4))-induced liver fibrosis in mice. Male Balb/C mice were treated with CCl(4) dissolved in olive oil (20%, v/v, 2mL/kg) intraperitoneally (i.p.), twice a week for 7 weeks. Delphinidin was administered i.p. once daily for next 2 weeks, in doses of 10 and 25mg/kg of body weight. The CCl(4) control group has been observed for spontaneous reversion of fibrosis. CCl(4)-administration induced an elevation in serum transaminase and alkaline phosphatase levels and increased oxidative stress in the liver. Delphinidin has successfully attenuated oxidative stress, increased matrix metalloproteinase-9 and metallothionein I/II expression and restored hepatic architecture. Furthermore, the overexpression of tumor necrosis factor-alpha and transforming growth factor-beta1 has been withdrawn by delphinidin. Concomitantly, the expression of alpha-smooth muscle actin indicated returning of hepatic stellate cells (HSC) into inactive state. Our results suggest the therapeutic effects of delphinidin in CCl(4)-induced liver fibrosis by promoting extracellular matrix degradation, HSC inactivation and down-regulation of fibrogenic stimuli, with strong enhancement of hepatic regenerative capability.