acetylcysteine

N-Acetylcysteine-Induced Hepatotoxicity and Urticaria in a 9-Year-Old Girl.

El-Qurneh Omaima O, Suhasini Macha M

N-acetylcysteine (NAC) is increasingly used off-label in pediatric populations to manage psychiatric disorders, particularly repetitive behaviors and anxiety-related conditions. Although generally considered safe, rare but serious adverse reactions, including hepatotoxicity, have been reported. This report describes a 9-year-old girl with anxiety and attention-deficit/hyperactivity disorder who developed severe transaminitis and urticaria following NAC therapy prescribed for skin-picking behavior. The patient presented with peak alanine aminotransferase of 1,417 U/L and aspartate aminotransferase of 541 U/L and a diffuse urticarial rash that developed 5 days after NAC initiation. Complete resolution occurred within 3 weeks of discontinuing NAC. This case highlights the potential for serious hepatotoxicity associated with NAC in pediatric patients, emphasizing the importance of baseline liver function monitoring and education regarding early signs of adverse reactions when using NAC off-label for psychiatric indications.

Particulate Matter Induces Apoptotic Death of Brain Vascular Endothelial Cells in Association with Oxidative Damage, DNA Damage Response, and MAPK/NF-κB Signaling.

Lee Chae Hwan CH, Kim Seok-Hyung SH, Choe Seong-Kyu SK, Cha Hanvit H

Particulate matter (PM) is associated with cerebrovascular and neurological disorders, but the responses of brain vascular endothelial cell (BVEC) to PM remain incompletely understood. PM10 reduced BVEC viability and increased cell death, TUNEL labeling, and cleaved caspase-3 and PARP, accompanied by increased intrinsic and death receptor-associated apoptotic proteins, DNA damage response markers, MAPK/NF-κB signaling components, and lipid and protein oxidation markers. N-acetylcysteine (NAC) pretreatment improved cell survival and reduced apoptosis-associated protein cleavage, supporting a contribution of NAC-sensitive, redox-related processes. In zebrafish, PM10 caused concentration-dependent developmental toxicity and altered brain vascular phenotypes. These findings support a working model in which oxidative damage and stress-responsive signaling are associated with apoptotic injury in BVEC; their causal relationships require further investigation.

Platelet lysates ameliorate impaired neuronal autophagy in Parkinson's Disease: correlative evidence for ROS/Akt signaling.

Yu Jingjing J, Tang Zongsheng Z, Lu Jiangtao J, Song Shuhong S et al.

Parkinson's disease (PD) is the second most common neurodegenerative disorder and represents a growing global health challenge. Platelet lysates (PLs) are enriched in growth factors, cytokines, and bioactive proteins with known tissue-regenerative and neurorestorative properties; however, their neuroprotective efficacy and molecular mechanisms in PD remain unclear. This study aimed to investigate the neuroprotective effects of PLs in PD models and to explore the underlying mechanisms. SH-SY5Y cells exposed to 6-OHDA, MPP⁺, or rotenone were used as in vitro PD models. Cell viability, morphological injury, ROS levels, TH expression, and p-α-syn (Ser129) levels were assessed. Autophagosome formation was evaluated using an Ad-GFP-LC3 transduction assay, and autophagic flux was further verified by bafilomycin A1-mediated lysosomal blockade. Mechanistic studies employed SC79 (Akt activator) and N-acetylcysteine (NAC, ROS scavenger). In vivo, MPTP-induced and A53T transgenic mouse models of PD were used to evaluate nigrostriatal dopaminergic neuronal protection, Nissl body preservation, p-α-syn accumulation, and motor function. PLs ameliorated neurotoxin-induced morphological injury, increased cell viability, reduced intracellular ROS levels, upregulated TH expression, and decreased p-α-syn (Ser129) accumulation in SH-SY5Y cells. Ad-GFP-LC3 assays showed that PLs promoted autophagosome biogenesis, and bafilomycin A1-based flux assays further confirmed that PLs rescued neurotoxin-impaired autophagic flux across all three toxin models. Mechanistically, PLs consistently reduced ROS and enhanced Akt phosphorylation. In MPP⁺- and 6-OHDA-injured cells, this was accompanied by ATG5/LC3-II upregulation and restoration of autophagic degradation; however, in the rotenone model, the toxin-induced ATG5 reduction was not significantly reversed despite effective attenuation of oxidative stress and p62 accumulation, suggesting ATG5-independent protective mechanisms. In vivo, PLs administration protected nigrostriatal dopaminergic neurons, preserved Nissl bodies, reduced p-α-syn (Ser129) immunoreactivity, and improved motor function in both MPTP-induced and A53T transgenic mouse models of PD. PLs attenuate neurotoxin-induced neuronal injury and improve pathological and behavioral phenotypes in PD models. The ROS/Akt signaling axis appears to be one plausible mechanistic correlate of PLs-mediated neuroprotection, with toxin-specific divergence in downstream autophagy mechanisms. These findings support further investigation of PLs as a potential intervention for PD-related pathological phenotypes.

N-Acetylcysteine for Clozapine-Associated Sialorrhea: A Case Report.

Kalyoncu Anil A, Swigart Alison A