RESUMEN
Zinc (Zn) is one of the most important essential nutrients of great public health significance. It is involved in numerous biological functions and it is considered as a multipurpose trace element, due to its capacity to bind to more than 300 enzymes and more than 2000 transcriptional factors. Its role in biochemical pathways and cellular functions, such as the response to oxidative stress, homeostasis, immune responses, DNA replication, DNA damage repair, cell cycle progression, apoptosis and aging is significant. Zn is required for the synthesis of protein and collagen, thus contributing to wound healing and a healthy skin. Metallothioneins are metal-binding proteins and they are potent scavengers of heavy metals, including Zn, and protect the organism against stress. Zn deficiency is observed almost in 17% of the global population and affects many organ systems, leading to dysfunction of both humoral and cell-mediated immunity, thus increasing the susceptibility to infection. This review gives a thorough insight into the most recent evidence on the association between Zn biochemistry and human pathologies, epigenetic processes, gut microbial composition, drug targets and nanomedicine.
Asunto(s)
Contaminantes Ambientales/toxicidad , Zinc/toxicidad , Envejecimiento , Animales , Apoptosis , Homeostasis , Humanos , Metalotioneína , Metales Pesados , Estrés Oxidativo , Preparaciones Farmacéuticas , Sustancias Protectoras , Factores de TranscripciónRESUMEN
Vitreous humor has become in recent years an important alternative biological fluid in forensic toxicological analysis especially for the investigation of cases where alcohol and drugs of abuse are involved but there is limited scientific information regarding the distribution of antidepressant drugs in this material. This work aimed to study the distribution of antidepressant drugs in vitreous humor and to estimate the blood/vitreous humor concentration ratios of these drugs. For this purpose, a GC/MS method for the simultaneous determination of 9 antidepressant drugs, namely amitriptyline, nortriptyline, citalopram, clomipramine, fluoxetine, maprotiline, mirtazapine, sertraline and venlafaxine, and 4 of their metabolites, namely desmethylmaprotiline, desmethylmirtazapine, desmethylsertraline, O-desmethylvenlafaxine, was developed and validated. The developed method includes solid-phase extraction followed by derivatization with Heptafluorobutyric Anhydride. For all analytes, LOD and LOQ were 1.50 and 5.00ng/mL, respectively, and the calibration curves were linear within the dynamic range of 5.00-500.0ng/mL (R2≥0.990). The absolute recovery was found to be ≥86.3 % for all analytes. The accuracy (%Er) was found to range between -6.58 and 6.18 %, whereas the precision (%RSD) was less than 10.9 % for all analytes. The developed method was successfully applied to vitreous humor samples from 43 blood positive cases for antidepressant drugs. Whenever antidepressant drugs were detected in blood, they were also detected in the respective vitreous humor samples. The vitreous humor/blood concentration ratios were also calculated and were found to range from 0.04-7.07. Citalopram, mirtazapine, and its metabolite desmethylmirtazapine as well as venlafaxine and its metabolite O-desmethylvenlafaxine were the most identified substances in these samples (n≥4) and their results were better statistically evaluated. Our results suggest that vitreous humor could be an appropriate matrix for the determination of antidepressants in postmortem toxicology.