Chuturgoon, Anil Amichund.Ghazi, Terisha.Govender, Anthia Camara.2026-03-102026-03-1020242024https://hdl.handle.net/10413/24316Masters Degree. University of KwaZulu-Natal, Durban.Fumonisin B1 (FB1) is acknowledged as the most toxic variant of the Fusarium mycotoxins, largely due to its prevalence as a major naturally occurring fumonisin in agricultural products. The consumption of FB1 is associated with significant health risks for humans and animals. FB1 induces mitochondrial toxicity through the disruption of the mitochondrial electron transport chain (ETC), leading to mitochondrial membrane depolarization and an increase in reactive oxygen species (ROS) production. The aim of this investigation was to examine the mitochondrial toxicity in the lung tissue of mice treated with FB1 for 24 hours, along with the effects of FB1 on oxidative stress, mitophagy, and global DNA methylation. C57BL/6 mice (n=5/group) were orally administered 0.1 M phosphatebuffered saline (PBS) or 5mg/kg FB1 for 24 hours. Thereafter, the lungs were harvested, and RNA and protein were extracted. The TBARS assay was employed to measure lipid peroxidation. qPCR was used to corroborate the mRNA expression of oxidative stress-related genes [superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT) and glutathione peroxidase (Gpx)], mitochondrial stress mitigating and mitophagy related genes [sirtuin 3 (Sirt3), Lon peptidase 1 (Lonp1), PTEN-induced kinase 1 (Pink1), sequestosome 1 (p62), and Parkin] and DNA methylation-related genes [DNMT1, DNMT3A,DN MT3B and methyl-CpG-binding domain (MBD2)]. Western blot was used to establish the protein expression of SOD2, CAT, Sirt3, Lonp1 and Parkin. Global DNA Methylation was assessed by ELISA. Malondialdehyde (MDA) was significantly upregulated (p<0.0001) in the lung tissue of FB1- treated mice. Further, there was a marked decrease in the expression of antioxidant defence-related genes, including Nrf2 (p<0.0001), SOD1 (p=0.0003), and Gpx (p=0.0004). Additionally, there was a notable decrease in both the gene (p<0.0001) and protein (p<0.0001) expression of CAT, while SOD2 gene (p=0.7454) and protein (p=0.7141) expression did not show significant variation in the lungs of the treated mice, when compared to the controls. In terms of the mitochondrial stress response, FB1 significantly increased Sirt3 transcripts (p=0.0244) and protein expression (p=0.0001), coupled with a significant decrease in Lonp1 gene (p<0.0001) and protein (p<0.0001) levels. Moreover, following FB1 treatment, significant reductions were observed in the expression of Pink1 (p<0.0001), Parkin(p =0.0162), and p62 (p<0.0001) genes, alongside a significant decrease in Parkin protein (p<0.0001) expression. Finally, a significant increase in both global DNA methylation (p=0.0018) and expression of DNMT3A (p=0.0082) and DNMT3B (p=0.0047) was noted; DNMT1 (p=0.1521) and MBD2 (p=0.6934) expressions showed no significant change in the lung tissue of FB1-treated mice, relative to controls. FB1 disrupted mitochondrial function and inhibited mitophagy in mouse lungs. Furthermore, it induced oxidative stress, that contributed to mitochondrial toxicity and global DNA hypermethylation.enCC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/Ceramide synthase.Cuprous ions.Electron transport chain.Hydrogen chloride.Superoxide radicals.Thesishttps://doi.org/10.29086/10413/24316