Chuturgoon, Anil Amichund.Foolchand, Ashmika.2026-03-062026-03-0620252025https://hdl.handle.net/10413/24312Doctoral Degree. University of KwaZulu-Natal, Durban.A frequently overlooked global health issue includes fungal and mycotoxin contamination, which infects many staple foods across the globe. Owing to its ubiquitous nature, long-term exposures to varying doses of mycotoxins pose major health concerns in humans and animals. Fumonisin B1 (FB1) is a toxic secondary metabolite commonly found in contaminated maize, known to induce various toxicities. This study investigated the effects of FB1 on inflammatory responses, oxidative stress, and global DNA methylation in human glioblastoma U87MG cells after a 24-hour exposure. The MTT assay was performed to determine the FB1 IC50 value in U87MG cells, which was used for all subsequent experiments. Following FB1 treatment, DNA, RNA and protein were extracted from U87MG cells and standardized. An ELISA was then conducted using the standardized DNA samples to assess DNA methylation status. cDNA, synthesized from standardized RNA, was used to measure gene expressions of DNA methyltransferases (DNMTs), methyl-CpG binding domain 2 (MBD2), superoxide dismutase 2 (SOD2), catalase (CAT), glutathione peroxidase (GPx), nuclear factor erythroid 2-related factor 2 (NRF-2), 8-oxoguanine glycosylase 1 (OGG1), interleukin (IL)-6, IL-10 and nuclear factor-kappa B (NF-kB), via qPCR. Standardized protein samples were diluted in sample buffer and analysed by western blot to evaluate protein expressions of DNMTs, MBD2, SOD2, CAT, mitochondrial transcription factor A (TFAM), IL-1β, tumour necrosis factor-alpha (TNF-α), brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). Inflammation is a key mechanism of host immune defense, which is triggered by pro-inflammatory cytokines and maintained by anti-inflammatory cytokines. In U87MG cells, FB1 significantly reduced the expression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and NF-κB while enhancing the expression of the anti-inflammatory cytokine IL-10. Additionally, it decreased the pro-inflammatory marker COX-2 and increased the anti-inflammatory brain marker BDNF. Oxidative stress, caused by the imbalance between free radicals and antioxidants, is a known cellular toxicity mechanism of FB1 which results in DNA damage, protein degradation and neurodegenerative diseases. Here, FB1 decreased lipid peroxidation and antioxidant responses of SOD2, CAT, GPx, and NRF-2, while also inhibiting oxidative DNA damage through regulation of the OGG1 gene. Mitochondria are susceptible to reactive oxygen species (ROS) attack due to oxidative stress, which leads to mitochondrial dysfunction and mutations in mitochondrial DNA. Although FB1 prompted the upregulation of Sirtuin 3 (SIRT3), lon protease 1 (LonP1), and heat shock protein (HSP60) to support mitochondrial health in U87MG cells, it simultaneously caused alterations in mitochondrial DNA by downregulating mitochondrial transcription factor A (TFAM). The regulation of gene expression by DNA methylation is suggested to influence biological processes including neurogenesis and the pathogenesis of brain disorders. FB1-treated U87MG cells displayed global DNA hypermethylation, evidenced by increased levels of 5-methylcytosine and elevated expressions of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), alongside a significant decrease in demethylase expression (MBD2), providing an alternative mechanism for FB1 toxicity. Taken together, this data suggests that FB1, over a short period of time, may initially act as a selective neuroprotective agent by modulating inflammation, oxidative stress and mitochondrial responses, while also highlighting its potential neurotoxic effects through mitochondrial dysregulation and global DNA methylation.enCC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/Bicinchoninic acid.Adenosine triphosphate.Blood-brain barrier.Dimethyl sulfoxideHydrogen peroxideThesishttps://doi.org/10.29086/10413/24312