PMID: 

J Crit Care. 2019 Aug ;52:208-212. Epub 2019 May 4. PMID: 31102938

Abstract Title: 

Immune function testing in sepsis patients receiving sodium selenite.

Abstract: 

PURPOSE: We examined in a longitudinal study the role of sodium selenite in sepsis patients in strengthening the immune performance in whole blood samples using immune functional assays.MATERIALS AND METHODS: This was a sub-study from a randomized, double blinded multicenter clinical trial (SISPCT) registered with http://www.clinicaltrials.gov (NCT00832039) and with data collected at our center. Full blood samples were incubated with various recall antigens and the supernatants were measured for their cytokine concentrations as markers for immune response. Data from days 0, 4, 7, 14, and 21 (from sepsis onset) were analyzed using a generalized least squares model in R to appropriately take the longitudinal structure and the missing values into account.RESULTS: From the 76 patients enrolled in the study at our center, 40 were randomized to selenium therapy and 36 to placebo. The analyses of immune response assay data showed no statistical difference between the selenium and placebo groups at each of the time points. There was however an overall dampening of cytokine release, which tended to recover over time in both groups.CONCLUSION: Selenium has long been an adjuvant therapy in treating sepsis. Recently, it was proven to not have beneficial effects on the mortality outcome. Using data from our center in this sub-cohort study, we identified no relative improvement in cytokine release of stimulated blood immune cells ex vivo from patients with selenium therapy over a three-week period. This offers a potential explanation for the lack of beneficial effects of selenium in sepsis patients.

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PMID: 

Oral Dis. 2020 May ;26(4):789-804. Epub 2020 Feb 10. PMID: 31975475

Abstract Title: 

Selenium: A sole treatment for erosive oral lichen planus (Randomized controlled clinical trial).

Abstract: 

Oral lichen planus (OLP) is a chronic disease with immune-mediated pathogenesis. Selenium (Se), an antioxidant, plays a role in modulating immunity. The aim of this clinical trial was to evaluate two Se forms (novel topical hydrogel and oral capsules), solely, in treating erosive OLP based on clinical evaluation and salivary oxidative stress markers. Patients were allocated into one of three groups: group I, topical corticosteroids; group II, topical Se; and group III, systemic Se. Treatment lasted for 6 weeks; patients were clinically evaluated at baseline, 6, and 12 weeks. Biochemical analysis for salivary malondialdehyde (MDA) and total antioxidant capacity (TAC) levels at baseline and 6 weeks was performed. There was a significant reduction in signs and symptoms in response to all treatmentmodalities. However, there was no significant difference among the three groups at 6 weeks. At 12 weeks, group II had significantly lower pain scores compared with group I. Salivary MDA levels showed a significant decrease in patients of group I and group III. TAC levels showed no significant difference in response to treatment. Selenium can be proposed as a treatment for OLP. Salivary MDA levels can be a biomarker for OLP disease severity.

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PMID: 

Crit Rev Biochem Mol Biol. 2019 12 ;54(6):484-516. Epub 2020 Jan 30. PMID: 31996052

Abstract Title: 

Selenium and selenoproteins in prostanoid metabolism and immunity.

Abstract: 

Selenium (Se) is an essential trace element that functions in the form of the 21st amino acid, selenocysteine (Sec) in a defined set of proteins. Se deficiency is associated with pathological conditions in humans and animals, where incorporation of Sec into selenoproteins is reduced along with their expression and catalytic activity. Supplementation of Se-deficient population with Se has shown health benefits suggesting the importance of Se in physiology. An interesting paradigm to explain, in part, the health benefits of Se stems from the observations that selenoprotein-dependent modulation of inflammation and efficient resolution of inflammation relies on mechanisms involving a group of bioactive lipid mediators, prostanoids, which orchestrate a concerted action toward maintenance and restoration of homeostatic immune responses. Such an effect involves the interaction of various immune cells with these lipid mediators where cellular redox gatekeeper functions of selenoproteins further aid in not only dampening inflammation, but also initiating an effective and active resolution process. Here we have summarized the current literature on the multifaceted roles of Se/selenoproteins in the regulation of these bioactive lipid mediators and their immunomodulatory effects.

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PMID: 

Drug Chem Toxicol. 2012 Apr ;35(2):141-8. Epub 2011 Nov 18. PMID: 22091876

Abstract Title: 

Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats.

Abstract: 

Gentamicin (GM) is a widely used antibiotic against serious, life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of selenium (Se) in GM-induced nephrotoxicity in rats. Experiments were done on 32 adult Wistar rats divided into four groups of 8 animals each. The GM group received gentamicin (100 mg/kg), whereas the GM+Se group received the same dose of GM and selenium (1 mg/kg) by intraperitoneal (i.p.) injections on a daily basis. Animals in the Se group, serving as a positive control, received only selenium (1 mg/kg) and the control group received saline (1 mL/day), both given i.p. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of selenium coadministration with GM. GM was observed to cause a severe nephrotoxicity, which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous selenium administration protected kidney tissue against oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by selenium pretreatment. The results from our study indicate that selenium supplementation attenuates oxidative-stress-associated renal injury by reducing oxygen free radicals and lipid peroxidation in GM-treated rats.

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PMID: 

Arch Toxicol. 2012 Oct ;86(10):1527-36. Epub 2012 Apr 12. PMID: 22526374

Abstract Title: 

Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats.

Abstract: 

The present study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced nephrotoxicity and oxidative stress in rats. We also investigated the effects of MT on induction of apoptotic cell death and its potential mechanisms in renal tissues in response to GM treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) MT (15 mg/kg/day), (3) GM (100 mg/kg/day), and (4) GM&MT. GM caused severe nephrotoxicity as evidenced by increased serum blood urea nitrogen and creatinine levels, increased renal tubular cell apoptosis, and increased Bcl2-associated X protein and cleaved caspase-3 protein expression. Additionally, GM treatment caused an increase in levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) protein expression in renal tissues. The significant decreases in glutathione content, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities and the increase in malondialdehyde content indicated that GM-induced tissue injury wasmediated through oxidative reactions. In contrast, MT treatment protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by the GM treatment. Histopathological studies confirmed the renoprotective effect of MT. These results indicate that MT prevents nephrotoxicity induced by GM in rats, presumably because it is a potent antioxidant, restores antioxidant enzyme activity, and blocks NF-κB and iNOS activation in rat kidney.

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PMID: 

Hum Exp Toxicol. 2019 Mar ;38(3):321-335. Epub 2018 Nov 20. PMID: 30458643

Abstract Title: 

Vitamin D attenuates gentamicin-induced acute renal damage via prevention of oxidative stress and DNA damage.

Abstract: 

BACKGROUND: Despite being one of the most nephrotoxic drugs, gentamicin (GM) remains a mainstay as a first-choice agent in a vast variety of clinical situations owing to its superlative efficiency as a broad-spectrum antibiotic in treating several life-threatening bacterial infections. This urgently calls for the need for in-depth analysis of the mechanisms governing GM-induced nephrotoxicity and entails the necessity of presenting novel protective agents capable of ameliorating those renal deleterious effects. The reactive oxygen species and redox-sensitive transcription factors in GM-induced nephrotoxicity have recently called attention.PURPOSE: This study has been designed to shed light on the possible mechanisms of GM-induced nephrotoxicity and to provide a consensus set of histopathological, immunohistochemical, genetic and biochemical parameters elucidating the protective role of vitamin D against this nephrotoxicity.METHODS: Twenty-four adult male albino rats were equally divided into four groups: group I (control group), group II (GM), group III (GM + vitamin D) and group IV (vitamin D only). Kidney function tests, histopathological examination, gene expression of nuclear factor 2, nuclear factor kappa beta (NF-κB) and western blot of NF-κB p65, assessment of glutathione peroxidase and nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase by ELISA, as well as immunohistochemical evaluation of inducible nitric oxide, malondialdehyde, 8-hydroxy 2 deoxyguanine and vitamin D receptor, have beencarried out.RESULTS: The kidney function deterioration, tissue oxidative stress development and the histopathological changes induced by GM were significantly attenuated by vitamin D administration.CONCLUSION: Vitamin D attenuates GM nephrotoxicity through its antioxidant properties and prevention of DNA damage.

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PMID: 

Wien Klin Wochenschr. 2019 Feb ;131(3-4):75-80. Epub 2018 Dec 12. PMID: 30542778

Abstract Title: 

Effect of 25-hydroxyvitamin D on Helicobacter pylori eradication in patients with type 2 diabetes.

Abstract: 

BACKGROUND: Various studies have reported a lower Helicobacter pylori eradication rate and a more frequent reinfection rate in type 2 diabetes mellitus (T2DM). Vitamin D has anti-inflammatory and immunoregulatory activity and the role of the vitamin D receptor (VDR) in the antimicrobial activity against H. pylori has been reported. When it comes to the risk factors of H. pylori eradication, the function of vitamin D is not always taken into account. The aim of this study was to assess the role of 25-hydroxyvitamin D in H. pylori eradication in T2DM.METHODS: In this retrospective study data from 160 patients with T2DM who underwent eradication therapy for H. pylori in Anhui Provincial Hospital between July 2015 and September 2017 were analyzed. According to eradication status, patients were divided into two groups, the successful eradication group (n = 124) and the eradication failure group (n = 36). The following information was obtained from participants' records before eradication treatment: age, sex, body mass index (BMI), duration of T2DM, prescription of medication use, smoking and drinking history. All patients were tested for glycated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL‑C), triglyceride (TG) and 25-hydroxyvitamin D (25-OHD) at baseline.RESULTS: The H. pylori was eradicated in 124 (77.5%) patients, while in 36 (22.5%) patients the treatment was unsuccessful. The eradication failure group had a lower mean vitamin D concentration than the group with successful eradication (15.09 ± 7.72 ng/ml vs. 19.87 ± 6.35 ng/ml, p = 0.004). The estimated odds ratio (OR) for eradication failure in individuals with serum vitamin D deficiency (30 ng/ml) were 1.489 (95% confidence interval, CI: 1.046-2.121, P = 0.027), Individuals with long duration of diabetes (≥10 years) had odds of eradication failure of 1.467 (95% CI: 1.017-2.114, P = 0.040) compared to subjects with short duration of diabetes (

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PMID: 

Int J Vitam Nutr Res. 2018 Dec ;88(5-6):244-250. Epub 2019 May 24. PMID: 31124408

Abstract Title: 

Cholecalciferol, Ergosterol, and Cholesterol Enhance the Antibiotic Activity of Drugs.

Abstract: 

: Background: This is the first report demonstrating the antibiotic-modifying activity of cholecalciferol.AIM: In this study, cholecalciferol was evaluated against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.METHODS: The antibacterial and modulatory effects of cholecalciferol, ergosterol, and cholesterol (8-512μg/mL) were evaluated by microdilution assay against multiresistant bacterial strains.RESULTS: Cholecalciferol, when combined with aminoglycosides, was more effective against P. aeruginosa, reducing the concentration of amikacin and gentamicin necessary to inhibit bacterial growth from 156.25 to 39.06μg/mL and from 39.06 to 9.76 μg/mL, respectively. It is possible that cholecalciferol, due to its lipid-soluble nature, had a lipophilic interaction with the cell membrane, enhancing antibiotic uptake. Cholesterol and ergosterol were used to see if the mechanism of action of cholecalciferol was similar to that of these lipid compounds. Ergosterol and cholesterol increased aminoglycoside activity, where the effect was greater with higher subinhibitory concentration of sterol.CONCLUSIONS: There is no reported study on the use of cholesterol and ergosterol as modulators of antibiotics or any other drug, making this the first study in this area highlighting the interaction between cholesterol, ergosterol, and cholecalciferol with regard to modifying aminoglycoside activity.

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PMID: 

J Dig Dis. 2019 Aug ;20(8):421-426. Epub 2019 Jul 3. PMID: 31145549

Abstract Title: 

Influence of serum vitamin D level on Helicobacter pylori eradication: A multi-center, observational, prospective and cohort study.

Abstract: 

OBJECTIVES: This study was designed to test whether serum vitamin D levels affected Helicobacter pylori (H. pylori) infection and eradication rates.METHODS: A multicenter observational prospective cohort study was conducted. A total of 496 H. pyloripositive (H. pylori) and 257 H. pylori-negative (H. pylori) patients were enrolled from four hospitals in China. Baseline serum vitamin D levels were measured and aC-urea breath test (UBT) was performed for all the participants. The H. pyloripatients were divided into two subgroups based on their serum vitamin D levels (

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PMID: 

PLoS Negl Trop Dis. 2019 07 ;13(7):e0007567. Epub 2019 Jul 11. PMID: 31295336

Abstract Title: 

Vitamin D deficiency is a potential risk factor for lipid Amphotericin B nephrotoxicity.

Abstract: 

Invasive fungal infections (IFI) is a worldwide serious health problem and Amphotericin B (AmB) has been considered the drug of choice for IFI treatment. Despite its efficacy, clinical use of AmB has been associated with renal toxicity. Some lines of evidence have shown that an extemporaneous lipid emulsion preparation of AmB (AmB/LE) was able to attenuate nephrotoxicity, presenting similar benefits at a lower cost. Studies have been demonstrating that hypovitaminosis D may hasten the progression of kidney disease and reflect on a worse prognosis in cases of drug-induced nephrotoxicity. In view of the high worldwide incidence of hypovitaminosis D, the aim of this study was to investigate whether vitamin D deficiency may induce AmB/LE-related nephrotoxicity. Wistar rats were divided into four groups: control, received a standard diet for 34 days; AmB/LE, received a standard diet for 34 days and AmB/LE (5 mg/kg/day) intraperitoneally in the last 4 days; VDD, received a vitamin D-free diet for 34 days; and VDD+AmB/LE, received a vitamin D-free diet for 34 days and AmB/LE as described. At the end of the protocol, animals were euthanized and blood, urine and renal tissue samples were collected in order to evaluate AmB/LE effects on renal function and morphology. Association of AmB/LE and vitamin D deficiency led to diminished glomerular filtration rate and increased tubular injury, evidenced by reduced renal protein expression of NaPi-IIa and TRPM6 leading to hyperphosphaturia / hypermagnesuria. VDD+AmB/LE rats also presented alterations in the PTH-Klotho-FGF-23 signaling axis, urinary concentrating defect and hypertension, probably due to an inappropriate activation of the renin-angiotensin-aldosterone system. Hence, it is important to monitor vitamin D levels in AmB/LE treated patients, since vitamin D deficiency induces AmB/LE nephrotoxicity.

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