Chronic alcohol consumption is a leading cause of acquired neurodegeneration with well-documented structural and ultrastructural brain alterations. This review analyzes the cellular and molecular mechanisms underlying alcohol neurotoxicity, integrating findings from animal models, human post-mortem studies, and neuroimaging investigations. Ethanol crosses the blood-brain barrier and generates toxic metabolites including acetaldehyde and reactive oxygen species, triggering oxidative stress, lipid peroxidation, and mitochondrial dysfunction. Chronic exposure induces glutamatergic and gamma-aminobutyric acid (GABA)ergic adaptations leading to excitotoxicity during withdrawal. Cell death occurs through apoptotic, necrotic, and necroptotic pathways, while microglial and astrocytic activation perpetuates neuroinflammation. Histopathological (HP) changes include selective neuronal loss in the prefrontal cortex, hippocampus, and cerebellum, dendritic simplification, and synaptic alterations. White matter pathology manifests as demyelination and axonal degeneration. Associated thiamine deficiency produces characteristic lesions in the mammillary bodies, thalamus, and cerebellar vermis. Neuroimaging techniques provide valuable HP correlates and biomarkers for disease monitoring. While some changes demonstrate partial reversibility with abstinence through remyelination and synaptic plasticity, extensive neuronal loss remains irreversible. Understanding these mechanisms is essential for developing neuroprotective therapeutic strategies.
Iulia Băluțoiu, Sorin-Nicolae Dinescu, A. Gresita et al.· Romanian journal of morpholo...· 0 citations
BACKGROUND AND OBJECTIVE
Formaldehyde (FA), classified as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC), constitutes a significant occupational hazard within hospital pathology service, where it remains the "gold standard" fixative for tissue preservation. Despite widespread recognition of its toxicological properties, the specific carcinogenic and non-carcinogenic health risks confronting pathology personnel subjected to chronic, low-level, and intermittent exposures remain incompletely characterized. This review synthesizes the current body of evidence regarding the cellular and molecular mechanisms of FA toxicity, histopathological (HP) alterations in target tissues, and associated occupational health risks among pathology staff. Study selection for review: A comprehensive literature search was conducted across PubMed∕MEDLINE, Web of Science, and Scopus databases, encompassing publications through December 2025. Studies were selected based on relevance to FA toxicity mechanisms, HP effects, and occupational exposure in pathology settings. Given the heterogeneity of study designs and outcomes, a narrative synthesis approach was adopted.
EVIDENCE SYNTHESIS
The synthesized evidence demonstrates that pathology personnel are routinely exposed to FA concentrations exceeding recommended occupational exposure limits (OELs). At the cellular level, FA exerts toxicity through deoxyribonucleic acid (DNA)-protein crosslink formation, oxidative stress induction, and inflammatory pathway activation. HP examination of exposed individuals reveals a characteristic progression from ciliary loss and goblet cell hyperplasia through squamous metaplasia to epithelial dysplasia in the nasal mucosa. Non-carcinogenic health effects, including respiratory symptoms and genotoxicity biomarker elevation, are highly prevalent. However, direct epidemiological evidence substantiating elevated cancer risk within this specific occupational cohort remains limited, mainly due to improper (occupational medicine) reporting.
CONCLUSIONS
This review confirms substantial non-carcinogenic health effects among pathology personnel, with documented HP alterations representing preneoplastic changes at the portal of entry. The mechanistic evidence supports biological plausibility for carcinogenic risk, though epidemiological confirmation specific to this workforce remains lacking, highlighting a critical research gap.
M. Șerbănescu, A. Rotaru-Zăvăleanu, Lucrețiu Radu· Romanian journal of morpholo...· 0 citations