Jamshed Laiba, Marie-Lucas Amica, Perono Genevieve A, Tomy Gregg T, Petrik Jim J, Frank Richard A, Hewitt L Mark, Thomas Philippe J, Holloway Alison C
Department of Obstetrics & Gynecology, McMaster University, Hamilton, ON L8S 4L8, Canada.
Centre of Oil and Gas Research and Development, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
J Xenobiot. 2025 Apr 24;15(3):61. doi: 10.3390/jox15030061.
Altered body condition and diminished growth in wildlife in the Alberta Oil Sands Region (AOSR) are prompting investigations into the impact of oil sands industrial activity on wildlife in the region. Chemical constituents from bitumen-influenced waters, including oil sands process-affected water (OSPW), can disrupt endocrine signaling, leading to aberrant lipid accumulation and altered glycemic control in mammals. This study aimed to investigate the effects of naphthenic acid fraction components (NAFCs), derived from OSPW, on energy homeostasis using the McA-RH7777 rat hepatocyte model. Cells were exposed to NAFCs at nominal concentrations of 0, 0.73, 14.7, and 73.4 mg/L for 24 and 48 h. We assessed gene expression related to lipid and glucose metabolism and measured triglyceride accumulation, glucose, and fatty acid uptake. NAFC exposure (14.7 and 73.4 mg/L) reduced triglyceride levels and glucose uptake and increased fatty acid uptake and the expression of beta-oxidation genes, suggesting a metabolic switch from glucose to fatty acid oxidation. This switch in substrate availability signifies a shift in cellular energy dynamics, potentially linked to altered mitochondrial function. To investigate this, we conducted adenosine triphosphate (ATP), mitochondrial membrane potential, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays to measure cellular ATP levels, mitochondrial membrane potential, and apoptosis, respectively. At both time points, 73.4 mg/L NAFC exposure resulted in increased ATP levels, induced mitochondrial membrane hyperpolarization, and increased apoptosis. These results suggest that mitochondrial efficiency is compromised, necessitating metabolic adaptations to maintain energy homeostasis. Given that cells exhibit metabolic flexibility that allows them to dynamically respond to changes in substrate availability, we further demonstrated that the kynurenine-tryptophan ratio (KTR) serves as a marker for a shift in energy metabolism under these stress conditions. This work provides a mechanistic framework for understanding how bitumen-derived organic contaminants may disrupt metabolic function in wildlife living in the AOSR. These findings further support the use of molecular markers like KTR to evaluate sub-lethal metabolic stress in environmental health monitoring.
艾伯塔油砂地区（AOSR）野生动物身体状况的改变和生长的减缓，促使人们对油砂工业活动对该地区野生动物的影响展开调查。来自受沥青影响水体的化学成分，包括油砂加工影响水（OSPW），能够干扰内分泌信号，导致哺乳动物体内异常的脂质积累和血糖控制改变。本研究旨在利用McA-RH7777大鼠肝细胞模型，探究源自OSPW的环烷酸馏分成分（NAFCs）对能量稳态的影响。将细胞暴露于名义浓度为0、0.73、14.7和73.4 mg/L的NAFCs中24小时和48小时。我们评估了与脂质和葡萄糖代谢相关的基因表达，并测量了甘油三酯积累、葡萄糖和脂肪酸摄取情况。NAFC暴露（14.7和73.4 mg/L）降低了甘油三酯水平和葡萄糖摄取，并增加了脂肪酸摄取以及β-氧化基因的表达，表明代谢从葡萄糖氧化转变为脂肪酸氧化。底物可用性的这种转变意味着细胞能量动态的改变，可能与线粒体功能改变有关。为了对此进行研究，我们进行了三磷酸腺苷（ATP）、线粒体膜电位和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）试验，分别用于测量细胞ATP水平、线粒体膜电位和细胞凋亡情况。在两个时间点，73.4 mg/L的NAFC暴露均导致ATP水平升高、诱导线粒体膜超极化并增加细胞凋亡。这些结果表明线粒体效率受到损害，需要进行代谢适应以维持能量稳态。鉴于细胞表现出代谢灵活性，使其能够动态响应底物可用性的变化，我们进一步证明犬尿氨酸 - 色氨酸比值（KTR）可作为这些应激条件下能量代谢转变的标志物。这项工作为理解源自沥青的有机污染物如何扰乱生活在AOSR地区野生动物的代谢功能提供了一个机制框架。这些发现进一步支持使用像KTR这样的分子标志物来评估环境健康监测中的亚致死代谢应激。
