Subacute exposure to thallium disrupts renal energy metabolism by impairing the function of subcellular organelles in aged mice of both sexes

Thallium, a highly poisonous heavy metal, accumulates in the kidneys, causing damage that impairs its renal elimination. However, the adverse cellular effects of thallium in the kidneys of older individuals, particularly the alterations in energy metabolism, remain unclear. In this study, we demonstrated that thallium exposure (10 ppm) for 4 weeks affected water intake and kidney weight (P < 0.05) in aged female mice, whereas it affected food intake and body weight (P < 0.05) in aged male mice. Transcriptome analysis revealed that thallium exposure induced a renal inflammatory response and metabolic changes in aged male and female mice. In aged male mice, fatty acid analysis of the kidneys revealed that thallium exposure significantly increased the relative abundances of C18:0 (P < 0.01), C15:1 (P < 0.05), and C20:4n6 (P < 0.01) and significantly decreased those of C16:1 (P < 0.001) and total monounsaturated fatty acids (P < 0.05). In aged female mice, thallium exposure significantly (P < 0.05) increased the relative abundances of C20:0, C24:0, and C18:3n3. Protein analyses revealed that thallium exposure inhibited glutamate metabolism, the TCA cycle, and fatty acid degradation in mitochondria and peroxisomes in aged female mice. Thallium inhibited the TCA cycle and fatty acid degradation in peroxisomes in aged male mice. These findings establish that thallium exposure disrupts renal energy metabolism by impairing the function of subcellular organelles in aged female and male mice.