RESUMEN
Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson's disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson's disease. On the basis of the similarities, at histological level, between Wilson's disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.
Asunto(s)
Hígado/efectos de los fármacos , Hígado/lesiones , Zinc/farmacología , COVID-19/complicaciones , Quelantes/metabolismo , Cobre/metabolismo , Degeneración Hepatolenticular/complicaciones , Degeneración Hepatolenticular/tratamiento farmacológico , Degeneración Hepatolenticular/metabolismo , Humanos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , SARS-CoV-2/patogenicidad , Zinc/deficiencia , Zinc/metabolismo , Tratamiento Farmacológico de COVID-19RESUMEN
The cytochrome P450 (CYP450) superfamily is responsible for the metabolism of most xenobiotics and pharmacological treatments generally used in clinical settings. Genetic factors as well as environmental determinants acting through fine epigenetic mechanisms modulate the expression of CYP over the lifespan (fetal vs. infancy vs. adult phases) and in diverse organs. In addition, pathological processes might alter the expression of CYP. In this selective review, we sought to summarize the evidence on the expression of CYP focusing on three specific aspects: (a) the anatomical distribution of the expression in body districts relevant in terms of drug pharmacokinetics (liver, gut, and kidney) and pharmacodynamics, focusing for the latter on the brain, since this is the target organ of psychopharmacological agents; (b) the patterns of expression during developmental phases; and (c) the expression of CYP450 enzymes during pathological processes such as cancer. We showed that CYP isoforms show distinct patterns of expression depending on the body district and the specific developmental phases. Of particular relevance for neuropsychopharmacology is the complex regulatory mechanisms that significantly modulate the complexity of the pharmacokinetic regulation, including the concentration of specific CYP isoforms in distinct areas of the brain, where they could greatly affect local substrate and metabolite concentrations of drugs.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Encéfalo/enzimología , Encéfalo/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Evaluación Preclínica de Medicamentos , Interacciones Farmacológicas , Activación Enzimática , Inducción Enzimática , Humanos , Intestinos/enzimología , Riñón/enzimología , Hígado/enzimología , Farmacogenética , Xenobióticos/metabolismoRESUMEN
A significant percentage of costs in pharmaceutical markets is devoted to supplements due to the confidence of consumers in the beneficial effects of these products. Magnesium is one of the supplements with enduring and increasing popularity. According to what is reported online, this metal ion can cure or prevent almost all kinds of diseases. This review aims at illustrating a series of scientifically demonstrated cases in which magnesium was used in clinical practice. Except for its ordinary use as antacid and laxative, other ascertained uses, reported in scientific literature, consist of helping to treat several diseases such as nocturnal leg cramps, pre-eclampsia, diabetes, depression, Parkinson's and Alzheimer's disease, hypertension, some types of arrhythmias, asthma, migraine headaches, epilepsy, cerebral haemorrhage, and stroke. However, many of these promising uses of magnesium require further studies to define the involved molecular mechanisms which should help establishing its uses in relation to the prolonged use of supplements.
Asunto(s)
Trastornos Migrañosos , Preparaciones Farmacéuticas , Preeclampsia , Suplementos Dietéticos , Femenino , Humanos , Magnesio/uso terapéutico , EmbarazoRESUMEN
Depleted uranium (DU) is generally considered an emerging pollutant, first extensively introduced into environment in the early nineties in Iraq, during the military operation called "Desert Storm". DU has been hypothesized to represent a hazardous element both for soldiers exposed as well as for the inhabitants of the polluted areas in the war zones. In this review, the possible consequences on human health of DU released in the environment are critically analyzed. In the first part, the chemical properties of DU and the principal civil and military uses are summarized. A concise analysis of the mechanisms underlying absorption, blood transport, tissue distribution and excretion of DU in the human body is the subject of the second part of this article. The following sections deal with pathological condition putatively associated with overexposure to DU. Developmental and birth defects, the Persian Gulf syndrome, and kidney diseases that have been associated to DU are the arguments treated in the third section. Finally, data regarding DU exposure and cancer insurgence will be critically analyzed, including leukemia/lymphoma, lung cancer, uterine cervix cancer, breast cancer, bladder cancer and testicular cancer. The aim of the authors is to give a contribution to the debate on DU and its effects on human health and disease.
Asunto(s)
Neoplasias/inducido químicamente , Uranio , Humanos , Uranio/efectos adversos , Uranio/metabolismo , Uranio/farmacocinéticaRESUMEN
BACKGROUND AND OBJECTIVES: beta-thalassemia is an important public health problem in the countries bordering the Mediterranean sea. One of the major consequences of this disorder, primarily (due to an ineffective erythropoiesis) or secondarily to blood transfusions (which are necessary for the patient's survival), is iron storage. Applying X-ray microanalysis we wanted to demonstrate the different sites of iron storage in subcellular compartments (mitochondria, cytosol, nucleus, rough endoplasmic reticulum and lipid droplets) and whether there were any other trace elements stored in liver cell. DESIGN AND METHODS: X-ray microanalysis was performed (at 100 kV in the STEM mode of a Hitachi H7000) on thin sections from specimens of liver biopsies from 6 patients affected by b-thalassemia, during follow-up after bone marrow transplantation. RESULTS: Spectra showed no correlation between iron peaks of lysosomes and hepatic iron concentration (HIC) or serum ferritin levels. Iron peaks were also detected in other subcellular compartments such as cisternae of rough endoplasmic reticulum, mitochondria and cytosol. No iron peaks were detected in lipid droplets and no significant iron peaks were found in the nuclei. Traces of copper were almost constantly found in lysosomes and cytosol. INTERPRETATION AND CONCLUSIONS: These results demonstrated iron storage within subcellular organelles other than lysosomes and highlighted a non-correlation between lysosomal iron peaks and HIC or serum ferritin levels. The presence of traces of copper in the lysosomes and in the cytosol may be correlated with the stronger hypothesis of links in the metabolism of the two elements (iron and copper), as ceruloplasmin is a ferroxidase copper-dependent protein. X-ray microanalysis may become a relevant tool in the localization of iron storage within hepatocytes in the evaluation of the effectiveness of bone marrow transplantation and iron chelation therapy. It also may provide some interesting information about iron metabolism in hepatocytes.